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Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)
ctrrecruit@vcu.edu
NCT06311214
Inclusion Criteria:
* SCREENING PROTOCOL INCLUSION CRITERIA:
* Patients must have histologically confirmed solid tumor requiring therapy and meet one of the following criteria:
* Patients must have disease not amenable to curative-intent therapy OR
* Patients who have had disease progression after treatment with all available therapies for their disease that are known to confer benefit or are intolerant to such treatment will be eligible, if other eligibility criteria are met. If the patient is currently receiving therapy without progression, the clinician must have assessed that the current therapy is no longer benefitting the patient, or that the patient is not tolerating the therapy. Patients can be screened on ADC MATCH if they are on first-line treatment and expected to need a treatment change within 3 months, and ADC MATCH is felt to be appropriate next line therapy OR
* Patients with disease for which no standard treatment exists that has been shown to confer benefit OR
* Patients who are willing to forego standard therapies known to confer benefit
* NOTE: Patients can be on therapy at the time of initiating the Screening Protocol if the patient is interested in treatment on ADC MATCH upon progression, and the physician deems this appropriate
* Patient must have undergone RNA testing in a Clinical Laboratory Improvement Act (CLIA) environment. Patients who have high TOI RNA expression will have confirmation of TOI expression by CLIA IHC assay at MD Anderson Cancer Center (MDACC). Only patients with confirmed TOI protein expression will be eligible for assignment to a treatment cohort. Retrospective confirmation in another central laboratory may also be performed
* Patients must be willing to undergo mandatory pre-treatment and on-treatment tumor biopsies. Patients who do not consent to these research biopsies will not be eligible for prescreening. Patients who have screened and consented to a treatment cohort but are found to have disease that cannot be safely biopsied will be eligible for treatment provided all other eligibility criteria are met
* Patients must have measurable disease
* Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of the Cancer Therapy Evaluation Program (CTEP) investigational new drug (IND) agents to be used in the study in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group performance status of 0-2 (Karnofsky ≥ 50%)
* No history of transfusion dependence
* No history of persistent bone marrow suppression (absolute neutrophil count ≥ 1,500/mL and platelets ≥ 100,000/mL not attributable to active therapy; patients currently on bone marrow suppressive therapy can undergo assessment for the screening protocol but cannot be treated on any of the treatment cohorts unless bone marrow suppression is reversed off the suppressive therapy)
* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤ 3 × ULN
* Aspartate transaminase (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine transaminase (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 × institutional ULN. Transaminases up to 5 × ULN in the presence of liver metastases are not allowed to initiate the screening protocol but are allowed for the treatment cohorts
* Creatinine ≤ institutional ULN OR glomerular filtration rate ≥ 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2
* Patients must have albumin ≥ 3 g/dL
* Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this study
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational agents are eligible for this study
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this study, patients should be class 2B or better
* Women of childbearing potential must have a negative human serum pregnancy test result at the screening protocol
* The effects of the study drugs on the developing human fetus are unknown. For this reason and because investigational agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completion of study drug administration (unless otherwise indicated in the eligibility section of the treatment cohort protocols). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after completion of study drug administration
* Ability to understand and the willingness to sign a written informed consent document
* ADDITIONAL INCLUSION CRITERIA FOR TREATMENT COHORTS:
* Women of childbearing potential must have a negative serum pregnancy test result at treatment cohort screening
* Hemoglobin \> 9.0 g/dL
* Leukocytes ≥ 3000/mL
* Absolute neutrophil count ≥ 1,500/mL
* Platelets ≥ 100,000/mL
* Patient must be willing to sign the relevant treatment cohort consent form
* COHORT A INCLUSION CRITERIA:
* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort A registration
* Patient must have high Trop-2 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay
* Patients who have Trop-2 IHC testing without RNA testing or who have Trop-2 IHC 2 or 3+ expression but do not have Trop-2 expression detected on RNA testing will not be eligible for the trial.
* Patients who have Trop-2 RNA expression and Trop-2 IHC 2+ or 3+ on another Trop-2 IHC test will undergo Trop-2 testing with the integral MDACC IHC assay
* Patients who already have RNA expression testing demonstrating Trop-2 RNA expression as well as IHC testing on the MDACC CLIA lab platform will be eligible for enrollment after review of results by the Precision Oncology Decision Support team without having to repeat Trop-2 IHC results as part of pre-screening. Patients who have had TROP2 2+ testing result performed outside of MDACC will have to undergo MDACC TROP2 IHC analysis before enrollment
* COHORT B INCLUSION CRITERIA:
* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort B registration
* Patient must have high Nectin-4 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay
* COHORT C INCLUSION CRITERIA:
* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort C registration
* Patient must have HER2 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center (MDACC) IHC assay
* Patients who have HER2 IHC testing without RNA testing or who have HER2 IHC 2 or 3+ expression but do not have HER2 expression detected on RNA testing will not be eligible for the trial
* Patients who have HER2 RNA expression and HER2 IHC 3+ or 2+ on another HER2 IHC test will undergo HER2 testing with the integral MDACC IHC assay
* Patients who already have RNA expression testing demonstrating HER2 RNA expression as well as IHC testing on the MDACC CLIA lab platform will be eligible for enrollment after review of results by the Precision Oncology Decision Support team without having to repeat HER2 IHC results as part of pre-screening. Patients who have had HER2 2+ testing result performed outside of MDACC will have to undergo MDACC HER2 IHC analysis before enrollment
* Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after completion of study drug administration. Women should not breastfeed during the study treatment period and for 7 months after completion of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of study drug administration. Female patients must not donate, or retrieve for their own use, ova from the time of screening throughout the study treatment period and for at least 7 months after the final study drug administration. Female patients may wish to consider preservation of ova prior to enrollment in the study. Male patients should refrain from freezing or donating sperm during the study and for 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in the study
* LVEF ≥50% within 28 days before enrollment
Exclusion Criteria:
* SCREENING PROTOCOL EXCLUSION CRITERIA:
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease. Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks after central nervous system-directed therapy shows no evidence of progression
* Clinically significant cardiovascular condition including: (1) history of congestive heart failure (New York Health Association class \> 2), (2) any history of unstable angina, (3) myocardial infraction within the past 12 months, or (4) any history of supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention
* History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
* Active or chronic corneal disorder including, but not limited to, Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and/or active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the ADCs used in the study
* History of interstitial lung disease or pneumonitis requiring steroid therapy
* Grade 2 or greater peripheral neuropathy
* Patients requiring the use of full dose coumarin-derivative anticoagulants such as warfarin. Low molecular weight heparin is permitted for prophylactic or therapeutic use. Factor X inhibitors are permitted
* Note: Warfarin may not be started while enrolled in the treatment cohorts. Stopping the anticoagulation for biopsy should be per site standard operating practice
* Pregnant women are excluded from the study because the study drugs are investigational or approved agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with any of the study drugs, breastfeeding should be discontinued if the mother is treated with any of the study drug
* ADDITIONAL EXCLUSION CRITERIA FOR TREATMENT COHORTS:
* Patients must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery; 4 weeks from antibody-based therapy; 2 weeks or 5 half-lives (whichever is shorter) from any targeted therapy or small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive radiotherapy, mitomycin C, and nitrosoureas); and 4 weeks from radiation therapy. Patients should have received no more than 3 prior lines of chemotherapy. Testosterone suppression as supportive treatment for castration-resistant prostate cancer and ovarian suppression in premenopausal patients with breast cancer that have supportive treatment and not anticancer treatment role (with luteinizing hormone-releasing hormone analogs) will be allowed if the patients were on these supportive treatments before starting the study. Use of bone-modifying medications (bisphosphonates or denosumab) will be allowed. Palliative radiotherapy of non-target lesions is permitted, but presence of new or worsening metastases will be considered progressive disease. If there is clear evidence of clinical benefit, study treatment may be continued 2 weeks after completion of palliative radiotherapy to lesions that are non-target lesions. Patients can be on therapy during treatment cohort screening
* Patients who are currently receiving any other investigational agent(s)
* Received systemic therapy with corticosteroids at \> 20 mg/day prednisone or equivalent within 1 week prior to cycle 1 day 1
* Patients who have not recovered from AEs due to prior anticancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* When the corrected QT interval (QTc) by Fridericia's formula is \< 120 ms, \> 450 ms in males and \> 470 ms in females. When the QTc by Rautaharju's formula is ≥ 120 ms, \> 450 ms in males and \> 470 ms in females
* Uncontrolled infection requiring intravenous antibiotic, antiviral, or antifungal use
* Received a live, attenuated vaccine within 30 days prior to cycle 1 day 1. Enrolled patients should not receive live vaccine during the study. Non-live COVID vaccines will be allowed on study, but it is recommended to avoid their use during the first treatment cycle (from 3 days prior to cycle 1 day 1 through cycle 2 day 3)
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations
* COHORT A EXCLUSION CRITERIA:
* Patients with histologically documented advanced colorectal cancer, urothelial cancer, head and neck cancer, triple negative breast cancer (TNBC), HR-positive breast cancer, HER2-positive breast cancer, small cell lung cancer, NSCLC, and endometrial cancer
* Patients who have received growth factor support within 2 weeks of study treatment initiation
* Coadministration of sacituzumab govitecan (IMMU-132) with inhibitors of UGT1A1 may increase systemic exposure to the active metabolite, SN-38. UGT1A1 inhibitors should not be administered concomitantly with sacituzumab govitecan (IMMU-132) unless there are no therapeutic alternatives
* Prior topoisomerase 1 inhibitor treatment
* Prior treatment with a Trop-2-targeting ADC
* Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of treatment cohort A registration
* COHORT B EXCLUSION CRITERIA:
* Patients with histologically documented advanced urothelial cancer, head and neck cancer, breast cancer, lung cancer, gastric cancer, gastroesophageal junction cancer, esophageal cancer, prostate cancer, or penile cancer
* Concomitant use of strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4. Washout period is 2 weeks prior to study treatment initiation
* History of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes mellitus is defined as hemoglobin A1c ≥ 8% or hemoglobin A1c between 7 and \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
* Known active keratitis or corneal ulcerations. Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated
* Known hypersensitivity to enfortumab vedotin or to any excipient in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20), or known hypersensitivity to biopharmaceutical produced in Chinese hamster ovary cells
* Prior treatment with an ADC with vedotin payload
* COHORT C EXCLUSION CRITERIA:
* Patients with histologically documented advanced breast cancer, non-small cell lung cancer (NSCLC), colorectal carcinoma (CRC), gastric cancer, or gastroesophageal junction (GEJ) cancer
* Previous treatment with topoisomerase I inhibitors as a free form or as other formulations, and ADCs with topoisomerase I inhibitor payloads
* Patients receiving treatment with chloroquine or hydroxychloroquine are not allowed to participate in the study, unless there is a washout period of at least 14 days prior to the first dose of study drug
* History of non-infectious pneumonitis/interstitial lung disease (ILD), current ILD, or where suspected ILD that cannot be ruled out by imaging at screening
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of initiation of study drug, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion etc.)
* Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening
* Prior pneumonectomy
* History of severe hypersensitivity reactions to other monoclonal antibodies PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, OTHER: Electronic Health Record Review, DRUG: Enfortumab Vedotin, OTHER: Immunohistochemistry Staining Method, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, BIOLOGICAL: Sacituzumab Govitecan, BIOLOGICAL: Trastuzumab Deruxtecan
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
The Multicenter Stress Cardiac Magnetic Resonance Quantitative Perfusion Imaging in the United States Study (SPINS2)
Raymond Y Kwong, MD, MPH - rykwong@bwh.harvard.edu
NCT06854458
Inclusion Criteria:
• male or female at age 35-85 years,
• presence of either of the following sign/symptom that led to a referral to stress cardiac magnetic resonance imaging:
• chest pain or anginal equivalent, or
• abnormal electrocardiogram with a suspicion of coronary artery disease
• Intermediate or high risk of significant coronary disease based on at least 1 of the following conditions: a) patient age \> 45 for male, 50 for female b) Diabetes, hypertension, or hypercholesterolemia: by either history or medical treatment c) family history of premature coronary disease: first degree relative at age \<= 55 male and \<=65 female d) history of smoking of \> 10 packed-years e) post-menopausal state \>5 years f) any chronic inflammatory conditions d) Body mass index \> 30 e) Any medical documentation of coronary or peripheral artery disease
Exclusion Criteria:
• Acute myocardial infarction within the past 30 days prior to cardiac magnetic resonance imaging
• Confirmed diagnosis of any significant non-coronary cardiac conditions below:
• any severe-grade valvular heart disease,
• left ventricular ejection fraction \<40% from any known non-coronary causes,
• infiltrative cardiomyopathy,
• hypertrophic cardiomyopathy,
• pericardial disease with significant constriction, or
• active pregnancy,
• any competing conditions leading to an expected survival of \< 2 years
• contraindication to vasodilator (regadenoson or adenosine)
• metallic device or object that poses an magnetic resonance imaging safety hazard
• metallic device with a high likelihood of non-diagnostic cardiac magnetic resonance images
DIAGNOSTIC_TEST: Quantitative Myocardial Blood Flow Evaluation, DIAGNOSTIC_TEST: Qualitative Myocardial Blood Flow Evaluation, DRUG: Gadavist, DRUG: Vasodilator, DIAGNOSTIC_TEST: Blood draw for the laboratory assessment
Ischemic Heart Disease (IHD), Cardiac Magnetic Resonance Imaging, Myocardial Blood Flow
Myocardial Blood Flow, Cardiac Magnetic Resonance, Quantitative perfusion, Cardiovascular Outcomes
US National OCS Heart Perfusion (OHP) Registry
Raicca Haqqi - rhaqqi@transmedics.com
NCT05915299
Inclusion Criteria:
* N/A
Exclusion Criteria:
* N/A DEVICE: OCS Heart
Heart Transplant
C-SMART vs BE Well for Patients With Brain Tumors
Sarah Braun, Ph.D - sarah.braun@vcuhealth.org
NCT07224503
Patient
Inclusion Criteria:
* Patient of Virginia Commonwealth University Neuro-Oncology clinic
* Confirmed primary brain tumor diagnosis by histology or neuro-oncologist review of imaging
* At least one domain of neurocognitive function \>1.5 SD below the average or the individual's estimated premorbid functioning, using the expanded International Cognition and Cancer Task Force (ICCTF) clinical trials battery and Test of Premorbid Functioning62 for comparison; (3) \>1 month post brain surgery and/or radiation therapy, if applicable;
* Estimated premorbid intelligence \>75.
* Patients must be age 18+ and
* Primarily English speaking.
Patient Exclusion Criteria:
* Presence of major neurocognitive impairment that would prevent participation in the intervention, and/or severe aphasia, and/or inability to understand and provide informed consent
* Inability to attend weekly telehealth appointments
* Clinically significant insomnia symptoms coupled with report that insomnia is more interfering than cognitive symptoms
* \< 1 month post brain surgery and/or radiation therapy
* Unstable internet connection or an inability to work teleconferencing software. Participants will be supplied an iPad if they do not have an adequate device.
* Participants cannot have metal in their body as the MRI scan could cause them harm
* If female of childbearing years, they cannot be pregnant as the MRI scan may pose risk to the unborn fetus
Caregiver Inclusion Criteria
* Must enroll with a patient (see criteria above)
* Must be age 18+ and
* Primarily English speaking
Caregiver Exclusion Criteria
-N/A BEHAVIORAL: C-SMART, BEHAVIORAL: BE Well
Brain Tumor
Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early-Stage Triple Negative Breast Cancer
Alicia Aranda - aaranda@swog.org
NCT05929768
Inclusion Criteria:
* Participants must have histologically confirmed estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative breast cancer (TNBC) defined as ER \< 5%, PR \< 5%, and HER2 negative (per 2020 American Society of Clinical Oncology \[ASCO\] College of American Pathologists \[CAP\] guidelines)
* NOTE: Participants with weakly ER or PR positive disease, defined as ER and/or PR between 1-4% by immunohistochemistry, are eligible if adjuvant endocrine therapy is not recommended/planned by the treating physician
* Participants must have American Joint Committee on Cancer (AJCC) 8 anatomic tumor clinical stage either
* T2-T4, N0, M0 or
* T1-T3, N1-2, M0
* Note: All participants with clinically suspicious nodes must undergo core needle biopsy or fine needle biopsy per standard clinical practice to pathologically confirm nodal status
* Participants must have breast and axillary imaging with mammogram and/or ultrasound and/or magnetic resonance imaging (MRI) within 49 days prior to randomization
* Note: Participants with bilateral invasive breast cancer are eligible if both breast cancers are ER-negative, PR-negative, and HER2-negative provided they meet the other eligibility criteria
* Participants must not have T4/N+, any N3, or inflammatory breast cancer
* Participants must not have metastatic disease (M1)
* Participants must not have received prior systemic therapy or radiation therapy with curative intent for the current breast cancer
* Participants must not have had previous definitive ipsilateral breast surgery for the current breast cancer
* Participants must not have current or anticipated use of other investigational agents while participating in this study
* Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition as study agents
* Participants must not have severe hypersensitivity (\>= grade 3) to pembrolizumab or any of its excipients
* Participants must not have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
* Participants must not be currently participating in or have participated in a study of an investigational agent or used an investigational device within 28 days prior to randomization
* Participants must be \>= 18 years old
* Participants must have Zubrod performance status of 0-2
* Participants with evidence of peripheral neuropathy must have it at =\< grade 1, by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0, within 28 days prior to randomization
* Participants must have a complete medical history and physical exam within 28 days prior to randomization
* Hemoglobin \>= 9.0 g/dL or \>= 5.6 mol/L (within 28 days prior to randomization)
* (Criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks)
* Leukocytes \>= 3 x 10\^3/uL (within 28 days prior to randomization)
* Absolute neutrophil count \>= 1.5 x 10\^3/uL (within 28 days prior to randomization)
* Platelets \>= 100 x 10\^3/uL (within 28 days prior to randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN), OR direct bilirubin =\< IULN for participants with total bilirubin \> 1.5 x IULN (unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional IULN) (within 28 days prior to randomization)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
* Participants must have a serum creatinine =\< the IULN OR calculated creatinine clearance \>= 50 mL/min/1.73m\^2 using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants must have adequate cardiac function. Participants must have left ventricular ejection fraction \>= 50% as assessed by either echocardiography (ECHO) or multigated acquisition scan (MUGA) assessed within 28 days prior to registration. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at randomization and have undetectable viral load test on the most recent test results obtained within 6 months prior to randomization
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization, if indicated
* Note: No testing for Hepatitis B is required unless mandated by local health authority
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization, if indicated
* Note: No testing for hepatitis C is required unless mandated by local health authority
* Participants with history of diabetes must not have uncontrolled diabetes in the opinion of the treating investigator
* Participants must not have uncontrolled hypertension in the opinion of the treating investigator
* Participants must not have had a major surgery within 14 days prior to randomization. Participants must have fully recovered from the effects of prior major surgery in the opinion of the treating investigator
* Participants must not have severe or active infections within 14 days prior to Randomization, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia
* Participants must not have a diagnosis of immunodeficiency and be receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
* Participants must not have active autoimmune disease that has required systemic treatment in 2 years prior to randomization (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
* Participants must not have a history of (non-infectious) pneumonitis that required steroids, or has current (non-infectious) pneumonitis
* Participants must not have received a live vaccine within 30 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist \[registered trademark\]) are live attenuated vaccines and are not allowed
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the treatment regimen
* Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must have one (1) physical 4-5-micron single hematoxylin and eosin (H\&E) slide from the archival pretreatment diagnostic biopsy available for submission
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants who can complete questionnaires in English, Spanish, or French must be offered the opportunity to participate in the Patient-Reported Outcome study
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* As part of the registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cyclophosphamide, DRUG: Docetaxel, DRUG: Doxorubicin, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, PROCEDURE: Surgical Procedure
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Early Stage Triple-Negative Breast Carcinoma
A Study to Investigate the Efficacy and Safety of Bemdaneprocel in Adults Who Have Parkinson's Disease (exPDite-2)
Patient Engagement - clinicaltrials@bluerocktx.com
NCT06944522
Inclusion Criteria:
* Diagnosis of clinically established PD as defined by the International Parkinson and Movement Disorders Society
* Individual of any sex ≥45 to ≤75 years of age at informed consent
* Robust and clear response to DA therapy as defined by MDS-UPDRS Part III
* ≥4 and \<12 years from time of PD diagnosis at informed consent
* Must demonstrate responsiveness to levodopa therapy
* Receiving medical therapy for the treatment of PD symptoms
* ≥2.5 hours of daily OFF-time
* Vaccinated per current national guidelines or local practice for patients with altered immunocompetence
Exclusion Criteria:
* PD presenting with recurrent falls
* Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis, or clinical features suggestive of a neurodegenerative disease other than PD, including multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, or Lewy body dementia
* Any current or relevant previous history of serious, severe, or unstable physical, neurological, or psychiatric illness that may interfere with study participation, participant's safety, or assessment of endpoints per investigator's judgment
* History of gene therapy or cell therapy
* Prior treatment with intrajejunal or subcutaneous infusion therapies for PD
* Prior surgical or radiation therapy to the brain, including deep brain stimulation (DBS) and lesion therapy, or prior history of intradural spinal cord surgery
* Contraindication to surgery, general anesthesia, cell therapy, immunosuppression, or other required drugs, or anything that prevents use of PET or MRI
* Any active infection (including but not limited to HIV, HCV, HBV, CMV, syphilis, or tuberculosis) or condition that, in the opinion of the investigator could put the participant at significant risk from immunosuppression or impact the participant's ability to perform study assessments
* Current or previously active malignant disease within the past 5 years
* Chronic immunosuppressive therapy
* Receipt of another investigational therapy within 5 half-lives of the active treatment
* Pregnancy or breastfeeding BIOLOGICAL: bemdaneprocel, PROCEDURE: Sham surgery
Parkinsons Disease (PD)
exPDite-2, Cell Therapy, Cellular Therapy, Dopaminergic Neuronal Cell Therapy, Parkinsons Disease
Comparing Radiation Therapy to Usual Care for Patients With High-Risk Bone Asymptomatic Metastases, PREEMPT Trial
ctrrecruit@vcu.edu
NCT06745024
Inclusion Criteria:
* Patients with polymetastatic cancer defined as more than 5 sites of radiographically-evident systemic metastatic disease (excluding intracranial disease)
* "High-risk" asymptomatic bone metastasis(es) (Brief Pain Inventory \[BPI\] score of \< 5 on the "maximum" pain item) defined as fulfilling at least one of the following four high-risk criteria:
* Bulky site of disease in bone ( ≥ 2 cm);
* Disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints;
* Disease in long bones occupying up to 2/3 of the cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpals, phalanges); and/or
* Disease in junctional spine (C7-T1, T12-L1, L5-S1) and/or disease with posterolateral element (pedicles and/or facet joints) involvement
* NOTES: Patients may have up to 3 individual high-risk bone metastases enrolled in the study. Sternum, rib, and scapula are defined as flat bones so lesions in these locations would only be included if bulky
* Patients with any solid tumor type (excluding multiple myeloma)
* Patients must have systemic disease evaluation through standard of care diagnostic imaging, including either CT chest/abdomen/pelvis or body positron emission tomography (PET)/CT, with radiology report available
* Patients with treated brain metastases and no known leptomeningeal disease are eligible if these lesions have been treated prior to enrollment
* Age ≥ 18
* Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky performance status (KPS) ≥ 60
* No previous radiotherapy to the intended enrolled sites of disease
* No epidural spinal cord compression (ESCC) ≥ grade 1c (defined as deformation of the thecal sac with spinal cord abutment) at the enrolled bone metastasis(es)
* No prior fracture at the enrolled bone metastasis(es) OTHER: Best Practice, PROCEDURE: Biospecimen Collection, OTHER: Bone Metastases Treatment, PROCEDURE: Computed Tomography, PROCEDURE: Conventional Radiotherapy, PROCEDURE: Magnetic Resonance Imaging, OTHER: Patient Observation, OTHER: Questionnaire Administration, RADIATION: Stereotactic Body Radiation Therapy
Metastatic Malignant Neoplasm in the Bone, Metastatic Malignant Solid Neoplasm
Testing the Combination of an Anti-cancer Drug, Iadademstat, With Other Anti-cancer Drugs (Atezolizumab or Durvalumab) at Improving Outcomes for Small Cell Lung Cancer
ctrrecruit@vcu.edu
NCT06287775
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed small cell lung cancer (SCLC)
* Patients who have been treated with platinum etoposide chemotherapy plus either atezolizumab or durvalumab immunotherapy for at least 4 cycles, and no more than 6 cycles, with either a radiographic response or stable disease. Patients are eligible if a maximum of 2 cycles of atezolizumab or durvalumab were omitted with initial treatment
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of iadademstat in combination with atezolizumab and durvalumab in patients \<18 years of age, children are excluded from this study
* Body weight ≥ 50 kg
* Patient is able to swallow oral medications
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%). This assessment for eligibility will take place after patients have received 4 cycles of standard of care (SOC) chemotherapy-ICI
* Leukocytes ≥ 2,000/mcL
* Lymphocyte count ≥ 500/mcL
* Absolute neutrophil count ≥ 1,500/mcL
* Hemoglobin ≥ 9 g/dL
* Platelets ≥ 100,000/mcL
* Albumin ≥ 3 g/dL
* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN unless liver metastases are present, in which case it must be ≤ 5 × ULN
* Glomerular filtration rate (GFR) ≥ 45 mL/min
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases (no escalating steroid use) untreated brain metastases (≤ 5 mm without significant edema) are eligible. Brain metastases must not be new after completion of chemotherapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Pregnant women are excluded from this study because atezolizumab and durvalumab are monoclonal antibody agents with the potential for teratogenic or abortifacient effects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
* Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
* The effects of iadademstat, atezolizumab, and durvalumab on the developing human fetus are unknown. For this reason and because monoclonal antibody agents are known to be teratogenic, women of child-bearing potential and males with females of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to registration, for the duration of study participation, and for 150 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Females of childbearing potential must agree to:
* Use effective contraception during the trial and 150 days after the end of treatment.
* Practice true abstinence during the trial and 150 days after the end of treatment.
* Have a negative urine pregnancy test at screening.
* Not to donate or freeze egg(s) during the course of this study or within 150 days after receiving their last dose of study drug.
* Male patients even if surgically sterilized (i.e., status post-vasectomy) must agree to:
* Use effective contraception during the entire study treatment period and through 150 days after the last dose of study drug.
* Not to donate or freeze sperm during the course of this study or within 150 days after receiving their last dose of study drug.
* Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab and durvalumab, female participants who are breastfeeding must agree to discontinue breastfeeding. These potential risks may also apply to iadademstat
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion Criteria:
* Patients who receive maintenance ICI therapy prior to cycle 1, day 1
* Patients medicated with anti-depressants reported to have KDM1A/LSD1 inhibitory activity: Tranylcypromine or phenelzine
* Patients who have not recovered from grade ≥2 adverse events (AEs) due to prior anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
* Patients with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
* Patients who are receiving any other investigational agents or any other agent administered for the treatment of the patient's cancer within four half-lives or 4 weeks prior to registration, whichever is shorter
* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-α or interleukin \[IL\]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to cycle 1, day 1
* Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to registration or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
* Patients who have received acute, low dose, systemic immunosuppressant medications or one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible after Principal Investigator confirmation has been obtained.
* Patients who have received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenocortical insufficiency are eligible
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to iadademstat, atezolizumab, or durvalumab. In particular, a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric antibodies, fusion proteins, or Chinese hamster ovary cell products or to any component of the atezolizumab formulation
* Atezolizumab Concomitant Medication Considerations: Patients are not allowed to receive immunostimulatory agents, immunosuppressive medications, or herbal and natural remedies
* Durvalumab Concomitant Medication Considerations: Patients are not allowed to receive immunosuppressive medications, EGFR TKIs, or herbal and natural remedies
* Iadademstat Concomitant Medication Considerations: Patients are not allowed to receive prophylactic hematopoietic colony stimulating factors, any complementary or alternative medicine \[any of various systems of healing or treating disease (as non-prescription drugs, herbal medicine and homeopathy)\]. Use of these types of treatments must be terminated 1 week prior to registration
* History of allogenic organ transplantation
* Patients with active tuberculosis (TB)
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
* History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Unstable angina, symptomatic or otherwise uncontrolled arrhythmia (does not include stable, lone atrial fibrillation), Fridericia's correction (QTcF) \> 480 ms based on screening electrocardiogram (ECG), myocardial infarction ≤ 3 months prior to registration, cerebrovascular accidents ≤ 3 months before registration. Patient has congestive heart failure New York Heart Association (NYHA) class 2, 3 or 4 or patients with a history of congestive heart failure NYHA class 2, 3 or 4 in the past, unless a screening echocardiogram performed within 1 month prior to registration demonstrates a left ventricular ejection fraction that is ≥ 45%
* History or risk of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
* Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
* Patients with controlled Type 1 diabetes mellitus (HbA1c \< 8%) on a stable insulin regimen may be eligible.
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided all of the following conditions are met:
* Rash must cover less than 10% of body surface area (BSA).
* Disease is well controlled at baseline and only requiring low potency topical steroids.
* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids) within the previous 12 months.
* Any chronic skin condition that does not require systemic therapy.
* Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
* Patients with celiac disease controlled by diet alone
* Patients should not receive vaccines 30 days prior to registration. Patient is informed to not receive vaccines during treatment and through 30 days after the last dose of study treatment with the exception of seasonal influenza vaccines and vaccines intended to prevent SARS-CoV-2, pneumococcal infection and coronavirus disease 2019 (COVID-19). If a patient had received a live attenuated vaccine within 30 days of the first dose of trial treatment, eligibility should be discussed with the investigator
* Patient has had major surgery within 4 weeks prior to registration
* Patient has radiation therapy within 4 weeks prior to registration, excluding palliative and central nervous system (CNS) radiation
* Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of iadademstat. In addition, patients with enteric stomata are also excluded
* Patients with history of clinically significant bleeding, specifically any history of intracranial hemorrhage / hemorrhagic cardiovascular accident (CVA), or patients with gastrointestinal bleeding within the 3 months prior to registration
* Patients with known irreversible bleeding disorders or receiving antiplatelet therapy for other indications
* Patients with uncontrolled disseminated intravascular coagulation
* Patients who refuse or are unable to potentially receive blood products BIOLOGICAL: Atezolizumab, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, BIOLOGICAL: Durvalumab, PROCEDURE: Echocardiography Test, DRUG: Iadademstat, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan
Extensive Stage Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8
Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial - Part 2 (FASTEST Part 2)
Joseph P Broderick, MD - broderjp@ucmail.uc.edu
NCT07227246
Inclusion Criteria:
• Patients aged 18-80 years, inclusive
• Patients with spontaneous ICH
• Able to treat with study medication (rFVIIa/placebo) within 120 minutes of stroke onset or last known well with a positive spot sign on pretreatment CT angiography.
• Efforts to obtain informed consent per EFIC guidelines (U.S.) or adherence to country-specific emergency research informed consent regulations (Canada, Germany, Spain, Finland, U.K., Japan, Australia)
Exclusion Criteria:
• Score of 3 to 7 on the Glasgow Coma Scale
• Secondary ICH related to known causes (e.g., trauma, aneurysm, arteriovenous malformation (AVM), oral anticoagulant use (vitamin K antagonists or novel oral anticoagulants) within the past 7 days, coagulopathy, etc.)
• ICH volume \< 2 cc or ≥ 60 cc
• Blood filling 2/3 or more of one lateral ventricle of the brain, OR, blood filling at least 1/3 of both lateral ventricles.
• Pre-existing disability (mRS \> 2)
• Symptomatic thrombotic or vaso-occlusive disease in past 90 days (e.g., cerebral infarction, myocardial infarction, pulmonary embolus, deep vein thrombosis, or unstable angina)
• Clinical or EKG evidence of ST elevation consistent with acute myocardial ischemia
• Brainstem location of hemorrhage (patients with cerebellar hemorrhage may be enrolled)
• Refusal to participate in study by patient, legal representative, or family member
• Known or suspected thrombocytopenia (unless current platelet count documented above 50,000/μL)
• Unfractionated heparin use with abnormal PTT
• Pro-coagulant drugs within 24 hours prior to patient enrollment into the FASTEST trial (example, tranexamic acid or aminocaproic acid)
• Low-molecular weight heparin use within the previous 24 hours
• Recent (within 90 days) carotid endarterectomy or coronary or cerebrovascular angioplasty or stenting
• Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered
• Recent (within 30 days) participation in any investigational drug or device trial or earlier participation in any investigational drug or device trial for which the duration of effect is expected to persist until to the time of FASTEST enrollment
• Planned withdrawal of care or comfort care measures
• Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency, or psychological disorder)
• Known or suspected allergy to trial medication(s), excipients, or related products
• Contraindications to study medication
• Previous participation in this trial (previously randomized)
• Females of childbearing potential who are known to be pregnant or within 12 weeks post-partum and/or lactating at time of enrollment -
BIOLOGICAL: Recombinant Factor VIIa, BIOLOGICAL: Biological/Vaccine: Placebo
Intracerebral Hemorrhage
Intracerebral hemorrhage, recombinant factor VIIa
Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia (ORION-20)
Novartis Pharmaceuticals - novartis.email@novartis.com
NCT06597019
Inclusion Criteria:
* Male or female participants, 6 to \<12 years of age at screening
* HeFH diagnosed either by genetic testing or on phenotypic criteria
* Fasting LDL-C \>130 mg/dL (3.4 mmol/L) at screening
* For participants 8 to \<12 years, on an optimal dose of statin (investigator's discretion) unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe). For participants \<8 years, the use of background lipid-lowering treatment is based on investigator's discretion.
* Participants on lipid-lowering therapies (such as statin and/or e.g. ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation.
Exclusion Criteria:
* Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
* Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
* Homozygous familial hypercholesterolemia (HoFH)
* Body weight \<16 kg at the screening and/or randomization (Day 1) visit
* Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation \>3x ULN, or total bilirubin elevation \>2x ULN (except patients with Gilbert's syndrome)
* Pregnant or nursing females
* Recent and/or planned use of other investigational medicinal products or devices DRUG: Inclisiran, DRUG: Placebo
Familial Hypercholesterolemia - Heterozygous
Heterozygous familial hypercholesterolemia (HeFH),, LDL-cholesterol (LDL-C),, Children,, pediatric,, small interfering ribonucleic acid (siRNA),, inclisiran,, Familial Hypercholesterolemia,, Heterozygous FH,, Hypercholesterolemia,, Lipoprotein(a),, Hyperlipidemia,, Dyslipidemia,, Heart Failure,, Cardiovascular Diseases,, Cholesterol,, Aortic Stenosis
Ruxolitinib vs Prednisone as First-line Therapy for cGVHD Needing Systemic Therapy
Sarah Starr - Sarah.Starr@moffitt.org
NCT06660355
Inclusion Criteria:
* Age ≥ 18 years.
* Karnofsky performance status ≥60%.
* Patients with a diagnosis of chronic GVHD per NIH diagnostic criteria5 who are in need for first systemic therapy as per treating physician's discretion, Overlap chronic GVHD will be allowed.
* No new immune suppressive therapy added within preceding 2 weeks prior to study enrolment.
* Able to take oral medications.
* Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥30,000/mcL
• Hemoglobin ≥ 7 g/dL
• Bilirubin ≤ 3 times institutional upper limit of normal (ULN) unless attributable to GVH d. AST(SGOT)/ALT(SGPT) ≤5 × institutional ULN unless attributable to GVH e. creatinine clearance ≥30 ml/min * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
* Previously treated with systemic immune suppressive therapy for chronic GVHD (where the indication for start of that systemic immune suppressive therapy was chronic GVHD).
* Patients with clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 6 months, New York Heart Association class III or IV heart failure will be excluded.
* Relapse malignancy post- transplant.
* Active hepatitis B, hepatitis C and HIV will be excluded.
* Any uncontrolled infection at the time if enrollment will be excluded.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ruxolitinib.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women and lactating women are excluded from this study because of the potential for teratogenic or abortifacient effects and an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Ruxolitinib, breastfeeding should be discontinued if the mother is treated with Ruxolitinib.
* Current or history of active Tuberculosis. DRUG: Ruxolitinib, DRUG: Prednisone
Chronic Graft-Versus-Host Disease (cGVHD)
Multisite Inventory of Neonatal-Perinatal Interventions (MINI) Minimum Dataset
Matthew A Rysavy, MD, PhD - Matthew.A.Rysavy@uth.tmc.edu
NCT05685745
Inclusion Criteria:
* All local births with gestational ages of 22 weeks 0 days - 23 weeks 6 days, regardless of pregnancy outcome or neonatal intensive care (NICU) admission; AND
* All outborn NICU admissions with gestational age at birth of 22 weeks 0 days - 23 weeks 6 days
* Optional: Centers who desire to include data for NICU admissions of infants born \<22 weeks' gestation may also submit these data. Infant, Extremely Premature, Obstetric Labor, Premature, Premature Birth, Intensive Care, Neonatal, Intensive Care Units, Neonatal
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
Gwen Nichols, MD - gwen.nichols@lls.org
NCT05183035
Inclusion Criteria
* Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/Blood Cancer United territory).
* Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
* Participants must have one of the following:
• Children, adolescents, and young adults with AML without demonstrated FLT3/internal tandem duplication (ITD) mutation. Ideally, the status of the mutation needs to be proven in the current relapse. Nevertheless, patients with previous FLT3/ITD negative test from prior lines can be included based on local results in order to not delay the start of treatment.
• And participants must have AML which is either: * Untreated second relapse, in participants who are sufficiently fit to undergo another round of intensive chemotherapy, or * Untreated first relapse, in participants who cannot tolerate additional anthracycline containing chemotherapy per investigator discretion. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score). * Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]); * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial. * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If higher transaminases outside these ranges (up to 5x ULN) are due to a radiographically identifiable leukemia infiltrate, the participant will remain eligible. Transaminase elevation up to 5x ULN is also allowed in case of steatosis on echography.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving an investigational drug other than those specified for this study. * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * Known hepatitis C virus (HCV), hepatitis B virus (HBV) (known positive hepatitis B virus (HBV) surface antigen (HBsAg) results), or human immunodeficiency virus (HIV) infection. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per Clinical Trial Facilitation Group (CTFG) guidelines for the duration of study therapy and at least 30 days after last dose of venetoclax, or 7 months after gemtuzumab ozogamicin treatment, or for 6 months after the completion of all study therapy, whichever is longer. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and at least 30 days after last dose of venetoclax or 4 months after last dose of gemtuzumab ozogamicin, 6 months from the last dose of cytarabine, or 90-days after last exposure to any other chemotherapy, whichever is longer. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 3 or 4 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
• Children, adolescents, and young adults with AML without demonstrated FLT3/internal tandem duplication (ITD) mutation. Ideally, the status of the mutation needs to be proven in the current relapse. Nevertheless, patients with previous FLT3/ITD negative test from prior lines can be included based on local results in order to not delay the start of treatment.
• And participants must have AML which is either: * Untreated second relapse, in participants who are sufficiently fit to undergo another round of intensive chemotherapy, or * Untreated first relapse, in participants who cannot tolerate additional anthracycline containing chemotherapy per investigator discretion. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score). * Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]); * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial. * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If higher transaminases outside these ranges (up to 5x ULN) are due to a radiographically identifiable leukemia infiltrate, the participant will remain eligible. Transaminase elevation up to 5x ULN is also allowed in case of steatosis on echography.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving an investigational drug other than those specified for this study. * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * Known hepatitis C virus (HCV), hepatitis B virus (HBV) (known positive hepatitis B virus (HBV) surface antigen (HBsAg) results), or human immunodeficiency virus (HIV) infection. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per Clinical Trial Facilitation Group (CTFG) guidelines for the duration of study therapy and at least 30 days after last dose of venetoclax, or 7 months after gemtuzumab ozogamicin treatment, or for 6 months after the completion of all study therapy, whichever is longer. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and at least 30 days after last dose of venetoclax or 4 months after last dose of gemtuzumab ozogamicin, 6 months from the last dose of cytarabine, or 90-days after last exposure to any other chemotherapy, whichever is longer. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 3 or 4 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
DRUG: Fludarabine, DRUG: Cytarabine, DRUG: Gemtuzumab Ozogamicin, DRUG: Azacitidine, DRUG: Venetoclax
Acute Myeloid Leukemia
Venetoclax, Gemtuzumab Ozogamicin, Fludarabine, Cytarabine, Relapsed refractory, Azacitidine
Phase 2, Efficacy and Safety Study of ACP-204 in Lewy Body Dementia Psychosis
Kristin Kidd - Kristin.kidd@acadia-pharm.com
NCT07029581
Inclusion Criteria:
* Male or female ≥55 years to \<85 years of age at the Screening visit living in the community or, if permitted by local regulations, in an institutionalized setting
* Can provide written informed consent. If the subject is deemed not competent to provide informed consent, the following requirements for consent must be met:
• The subject's LAR must provide written informed consent.
• The subject must provide written (if capable) informed assent per local regulations. * Meets either the clinical criteria for Parkinson's disease with dementia as defined by the Movement Disorder Society's Task Force or the revised clinical criteria for probable dementia with Lewy bodies (DLB) by consensus criteria (Fourth consensus report of the DLB Consortium). * Meets the revised criteria for psychosis in major or mild neurocognitive disorder established by the International Psychogeriatrics Association
Exclusion Criteria:
* Is in hospice, is receiving end-of-life palliative care, or is bedridden
* Has psychotic symptoms that are primarily attributable to delirium, substance abuse, or a medical or psychiatric condition (e.g. schizophrenia, bipolar disorder, delusional disorder) other than dementia
* Is actively suicidal at Visit 1 (Screening) or Visit 2 (Baseline)
* Has a history or current evidence of a serious and/or significant unstable cardiovascular, respiratory, endocrine, gastrointestinal, renal, hepatic, hematologic, immunologic, genitourinary, psychiatric or neurologic (including stroke, chronic seizures, or clinically significant head injury) abnormality or disease or other medical disorder, including cancer or malignancies that could interfere with subject's ability to complete the study or comply with study procedures
* Has other clinically significant CNS abnormalities that are most likely contributing to the dementia or findings on MRI or CT DRUG: ACP-204, DRUG: Placebo
Lewy Body Dementia Psychosis
Immunotherapy After Surgery for People Who Have No Remaining Cancer Cells After Standard Treatment for Early-Stage Non-Small Cell Lung Cancer, INSIGHT Trial
ctrrecruit@vcu.edu
NCT06498635
Inclusion Criteria:
* Participants must have histologically or cytological confirmed diagnosis of clinical stage II-IIIB (excluding clinical N3 disease) non-small cell lung cancer (NSCLC)
* Participants must have had a complete (R0) resection of NSCLC (with appropriate lymph node sampling as defined by the National Comprehensive Cancer Network \[NCCN\] guidelines) within 84 days (12 weeks) prior to randomization. Acceptable types of surgical resection are: lobectomy, sleeve resection, bi-lobectomy, or pneumonectomy. Wedge resection is not allowed.
* Note the NCCN guidelines: N1 and N2 node resection and mapping is a routine component of lung cancer resections. It is recommended at a minimum one N1 and three N2 stations is sampled or complete lymph node dissection. Formal ipsilateral mediastinal lymph node dissection is indicated for participants undergoing resection for N2 disease
* Participants must have a pathologic complete response (pCR) (no viable tumor in the resected specimen or lymph nodes), as determined by local pathology review
* Participants must have a PD-L1 status result (e.g. \[\< 1% versus \>= 1% or unknown\])
* Participants must not have known EGFR mutations, or ALK gene fusion
* Participants must have received at least two cycles of neoadjuvant platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 therapy. The neoadjuvant treatment must be Food and Drug Administration (FDA) approved and standard of care as listed in NCCN guidelines
* Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for NSCLC treatment while receiving treatment on this study
* Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 28 days prior to randomization
* Participants must not have medical contraindications or severe adverse events to receiving anti-PD-1 or anti-PD-L1 therapy
* Participants must not have received post-operative radiation therapy (PORT) for NSCLC
* Participants must not have any unresolved toxicity National Cancer Institute (NCI) CTCAE grade ≥ 2 from previous anticancer therapy with the exception of alopecia, and vitiligo. Note, participants with grade ≥2 neuropathy may be included at the discretion of the treating investigator. Note, participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included at the discretion of the treating investigator
* Participant must be ≥ 18 years old at time of study entry
* Participants must have body weight \> 30 kg
* Participant must have Zubrod performance status of 0-2
* Participant must have a complete medical history and physical exam within 28 days prior to randomization
* Hemoglobin \> 9.0 g/dL (within 28 days prior to randomization)
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to randomization)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to randomization)
* Total bilirubin ≤ 1 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to randomization)
* Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 × institutional ULN (within 28 days prior to randomization)
* Participants must have a calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to randomization. For creatinine clearance formula see the tools on the Clinical Research Associate (CRA) Workbench https://txwb.crab.org/TXWB/Tools.aspx
* Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
* Participants with a known history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to randomization
* Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization, if indicated
* Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization, if indicated
* Participants must not have had an organ transplant
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participant must not have medical contraindications to receiving immunotherapy, including history of non-infectious pneumonitis that required steroids or active autoimmune disease that has required systemic treatment with disease modifying agents, corticosteroids or immunosuppressive drugs in the past two years. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intra-articular steroid injections are allowed
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method during protocol therapy and for 6 months following completion of protocol therapy with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen. Participants should not breastfeed during protocol therapy and for 6 months following completion of protocol therapy
* Participants must not have received a live or live attenuated vaccine within 28 days prior randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever rabies, Bacillus Calmette-Guerin (BCG) and typhoid vaccine. Seasonal influenza vaccines and coronavirus disease 19 (COVID-19) vaccines are allowed, however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated, and are not allowed
* Participants must be offered the opportunity to participate in specimen banking
* Participants who can complete FACT-L, FACT-BRM, and PRO-CTCAE questionnaires forms in English, or Spanish must agree to participate in the patient-reported outcome study
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, BIOLOGICAL: Durvalumab, OTHER: Patient Observation, OTHER: Questionnaire Administration
Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8
Testing Nivolumab and Ipilimumab Immunotherapy With or Without the Targeted Drug Cabozantinib in Recurrent, Metastatic, or Incurable Nasopharyngeal Cancer
ctrrecruit@vcu.edu
NCT05904080
Inclusion Criteria:
* Patients must have histologically documented nasopharyngeal carcinoma (NPC) regardless of World Health Organization (WHO) classification (keratinizing squamous cell carcinoma, non-keratinizing, or basaloid squamous cell carcinoma) and regardless of association with Epstein-Barr virus (EBV) and/or human papillomavirus (HPV)
* Recurrent, metastatic and incurable disease treated with platinum-gemcitabine and prior PD-1/L1 blockade (as first or second-line therapy) where immunotherapy was part of the most recent prior line of therapy
* Patients are eligible regardless of prior smoking history, p16 immunohistochemistry (IHC) status, PD-L1 expression status, EBV tumor status, EBV viral load at baseline, or tumor genomic alteration status
* Patients must have at least one measurable lesion (by RECIST v1.1) which has not been previously irradiated that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions as \>= 10 mm (\>= 1 cm) (and short axis for nodal lesions, LN \>= 15 mm) with CT scan, MRI, or calipers by clinical exam
* Patients may have had no more than 2 prior lines of prior systemic therapy for recurrent, metastatic NPC
* No prior VEGFR targeted therapy permitted
* Age \>= 18 years
* Eastern Cooperative Oncology Group Performance (ECOG) performance status 0-2
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* Hemoglobin \>= 9 g/dL
* Platelet count \>= 100,000/mm\^3
* Creatinine or creatinine clearance =\< 1.5 mg/dL or \>= 30 Modification of Diet in Renal Disease (MDRD)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN); except subjects with Gilbert syndrome who can have a total bilirubin \< 3 mg/dL
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGT\]) =\< 3 x upper limit of normal (ULN)
* Up to =\< 5 allowed with liver metastases
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test, per institution standard, done =\< 7 days prior to registration is required.
* Pregnant women are excluded from this study because nivolumab, ipilimumab, and cabozantinib are all Class C or D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with any of the study agents, breastfeeding should be discontinued if the mother is treated with as part of this study (in either arm)
* No active tumor bleeding: or radiographic evidence of major blood vessel infiltration as judged by the treating investigator
* Prior -anti-cancer therapy is allowed: Patients need to be recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), with the exception of alopecia. Any life-threatening events clearly attributable to prior immunotherapy exposure that have a high possibility of recurring should warrant exclusion: including severe pneumonitis, grade 4 bullous dermatitis/drug reaction with eosinophilia and systemic symptoms (DRESS), neurologic events such as autoimmune encephalitis transverse myelitis, and/or myocarditis. Maintenance hormonal replacement or long-term hormonal therapy exposure is permitted.
* No chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration. Palliative (limited-field) radiation therapy is permitted, if all of the following criteria are met:
* Repeat imaging demonstrates no new sites of bone metastases.
* The lesion being considered for palliative radiation is not a target lesion
* No patients with a prior malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Brain metastases allowed: Patients with treated brain metastases are eligible if follow-up brain imaging 3 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently receiving treatment, they are eligible if they have an undetectable HCV viral load
* Solid organ or tissue transplant is allowed: - subsequent therapy with nivolumab increases the risk of organ/tissue rejection. Patients must be instructed that it is crucial they stay in touch with their transplant team during treatment
* No active autoimmune disease: or history of autoimmune disease that might recur, and which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of
* Immune related neurologic disease,
* Multiple sclerosis,
* Autoimmune (demyelinating) neuropathy,
* Guillain-Barre syndrome (GBS),
* Myasthenia gravis;
* Systemic autoimmune disease such as SLE,
* Connective tissue diseases,
* Scleroderma, inflammatory bowel disease (IBD),
* Crohn's, ulcerative colitis,
* Patients with a history of toxic epidermal necrolysis (TEN),
* Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
* Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome, and psoriasis controlled with topical medication and patients with only positive serology, such as antinuclear antibodies (ANA) or anti-thyroid antibodies, should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* Pneumonitis should be evaluated for the nature of the disease process, need for treatment prior study treatment, and the risk of exacerbation with study treatment
* Able to swallow oral medication: No known medical condition causing an inability to swallow oral formulations of agents
* No condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study registration. Patients are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses \> 10 mg daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is permitted
* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel) is prohibited. Allowed anticoagulants are the following:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
* Concomitant use of any medications or substances that are strong inhibitors or inducers of CYP3A4 is discouraged; if unavoidable, the dose of cabozantinib on study should be adjusted accordingly. Any complementary medications (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study are prohibited PROCEDURE: Biospecimen Collection, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, BIOLOGICAL: Ipilimumab, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab
Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma, Stage IV Nasopharyngeal Carcinoma AJCC v8
Fluid Management of Acute Decompensated Heart Failure Subjects Treated With Reprieve System (FASTR-II) (IDE-G210258) (FASTR-II)
Annemarie Forrest - aforrest@reprievecardio.com
NCT06898515
Inclusion Criteria:
• Diagnosis of HF with expected hospitalization \>24 hours, with \>1 new or worsening symptom and \>2 physical examination, laboratory, or invasive findings of HF, and receiving or with plans to receive a HF-specific treatment
• ≥10 lb. (4.5 kg) above dry weight as estimated by health care provider.
• Current outpatient prescription for daily loop diuretic.
• Participants ≥ 22 years of age able to provide informed consent and comply with study procedures.
• Elevated risk of diuretic resistance, as indicated by at least one of the following: Baseline hypochloremia OR Urine output \<1L in the 6 hours following IV loop diuretic \>=40 mg furosemide equivalent OR Spot urine sodium \<100 mmol/L 1-2 hours after IV loop diuretic \>= 40 mg furosemide equivalent
Exclusion Criteria:
• Urologic issues that would predispose the participant to a high rate of urogenital trauma or infection with catheter placement or known inability to place a Foley catheter.
• Hemodynamic instability as defined by any of the following: sustained systolic blood pressure \<90 mmHg for \>15 minutes within the past 48 hours, use of IV vasopressors or inotropes within past 48 hours, and/or current or previous mechanical circulatory support within the last week.
• Uncontrolled arrhythmias defined as sustained HR \>130 beats/min for \>10 minutes within the past 48 hours.
• Severe lung disease with chronic home oxygen requirement \>2L/min.
• Acute infection with evidence of systemic involvement (e.g., clinically suspected infection with fever or elevated serum white blood cell count).
• Estimated glomerular filtration rate (eGFR) \<25 ml/min/1.73m2 (calculated with either MDRD or CKD-EPI) or current use of renal replacement therapy (RRT).
• Significant left ventricular outflow obstruction, severe uncorrected complex congenital heart disease, known severe stenotic valvular disease, severe infiltrative or constrictive cardiomyopathy or other diagnosis that would make aggressive decongestion unsafe.
• Current or recent (\< 30 days) type I myocardial infarction (e.g., acute coronary syndrome such as NSTEMI or STEMI from plaque rupture), coronary artery bypass surgery, or stroke. An isolated troponin elevation (e.g., from volume overload or demand ischemia) is not a reason for exclusion.
• Severe electrolyte abnormalities (e.g., serum potassium \<3.0 mEq/L, magnesium \<1.3 mEq/L or sodium \<125 mEq/L). Note: These are based on baseline/screening labs. Participants whose electrolyte levels are repleted cannot be reassessed for inclusion in the trial.
• Other concomitant disease or condition the investigator believes will make it difficult to follow instructions or comply with study procedures and/or follow-up visits, including expected prolonged hospitalization for reasons other than decongestive therapy
• Currently enrolled in an interventional trial (observational studies are permitted).
• Life expectancy less than 6 months.
• Women who are pregnant or breastfeeding.
DEVICE: Reprieve System, DRUG: furosemide infusion
Acute Decompensated Heart Failure
A Study to Compare Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone as Treatment in Participants With Mismatch Repair Proficient Endometrial Cancer (MK-2870-033/TroFuse-033/GOG-3119/ENGOT-en29) (TroFuse-033)
Toll Free Number - Trialsites@msd.com
NCT06952504
Key inclusion criteria include but are not limited to:
* Has a histologically confirmed diagnosis of primary advanced or recurrent endometrial carcinoma that has been confirmed as proficient mismatch repair (pMMR)
* Has radiographically evaluable disease, with measurable Stage III or either measurable or non-measurable Stage IV or recurrent disease per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1), as assessed by the investigator.
* Has received no prior systemic therapy for endometrial carcinoma except the following conditions as pre-specified by the protocol: 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of curative-intent, prior radiation with or without radiosensitizing chemotherapy if \>2 weeks before the start of induction treatment, or prior hormonal therapy for treatment of endometrial carcinoma that was discontinued ≥1 week before the start of induction treatment
Key exclusion criteria include but are not limited to:
* Has carcinosarcoma, neuroendocrine tumors or endometrial sarcoma, including stromal sarcoma, leiomyosarcoma, adenosarcoma, or other types of sarcomas
* Has endometrial carcinoma of any histology that is mismatch repair deficient (dMMR)
* Is a candidate for curative-intent surgery or curative-intent radiotherapy at the time of enrollment
* Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Human Immunodeficiency Virus-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Received prior therapy in any setting with any of the following: anti-programmed cell death 1 protein, anti-programmed cell death ligand 1, anti-programmed cell death ligand 2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor; trophoblast cell surface antigen 2-targeted antibody drug conjugate; or topoisomerase I inhibitor-containing antibody drug conjugate
BIOLOGICAL: Pembrolizumab, DRUG: Carboplatin, DRUG: Paclitaxel, DRUG: Docetaxel, BIOLOGICAL: Sacituzumab Tirumotecan
Endometrial Cancer
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Trophoblast cell surface antigen 2 (TROP2)
The Efficacy and Safety of Rilzabrutinib in Patients Aged 10 to 65 Years With Sickle-cell Disease (LIBRA)
Trial Transparency email recommended (Toll free for US & Canada) - contact-us@sanofi.com
NCT06975865
Inclusion Criteria:
* Participants who have been diagnosed with SCD.
* Participants who have had between ≥2 to ≤10 episodes of documented acute clinical VOC within 12 months of the screening visit.
* Participants who are either not on hydroxyurea and/or L-glutamine at the Screening Visit and does not plan to receive them during the course of the study or has received HU and/or L-glutamine for a minimum of 6 months. Participants on hydroxyurea and/or L-glutamine must have been on a stable weight-based dose level (mg/kg) for at least 3 months prior to the Screening Visit, with the intent to continue at the same weight-based dose level for the duration of the study, except for safety reasons.
* Participants with Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower.
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* For participants ≥10 to \<18 years of age: the parent(s)/legal guardian(s) must provide written informed consent prior to any study-related procedures being performed.
Exclusion Criteria:
* Participants are excluded from the study if any of the following criteria apply: Participants with medical history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for the past 3 years.
* Clinically relevant cardiac abnormality, in the opinion of the Investigator or electrocardiogram (ECG) findings.
* Participants with history of stroke, or history of abnormal transcranial doppler.
* Participants with uncontrolled or active HBV infection and/or HCV infection including those receiving antiviral therapy at the time of screening.
* HIV infection.
* A history of active or latent tuberculosis (TB)
* Positive COVID-19 molecular test.
* Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days and/or voxelotor (OXBRYTA®) within 30 days prior to the Screening visit.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. DRUG: Rilzabrutinib, DRUG: Placebo
Sickle Cell Disease
Anti-Lag-3 (Relatlimab) and Anti-PD-1 Blockade (Nivolumab) Versus Standard of Care (Lomustine) for the Treatment of Patients With Recurrent Glioblastoma
ctrrecruit@vcu.edu
NCT06325683
Inclusion Criteria:
* Histologically-proven glioblastoma (World Health Organization \[WHO\] 2021 criteria)
* Progressive or recurrent disease per Response Assessment in Neuro-Oncology (RANO) criteria
* No IDH mutation (IDH1 R132H negative by immunohistochemistry \[IHC\] or sequencing)
* Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide
* No prior therapies except radiation, surgery, temozolomide, Tumor Treating Fields (TTFields), and/or Gliadel wafers (placed during the first surgery at diagnosis of glioblastoma multiforme \[GBM\]). Prior radiation therapy, TTFields, or placement of Gliadel wafers must be completed at least 2 weeks prior to registration. Prior temozolomide must be completed at least 3 weeks prior to registration
* No prior use of nivolumab or other anti-PD1 agents
* Patients must be neurologically stable off corticosteroids for at least 5 days prior to registration
* Age: ≥ 18 years
* Karnofsky Performance Status: ≥ 60% (i.e. patient must be able to care for themselves with occasional help from others)
* Absolute lymphocyte count (ALC): ≥ 1000/mm\^3
* Absolute neutrophil count (ANC): ≥ 1500/mm\^3
* Platelet count: ≥ 100,000/mm\^3
* Hemoglobin: ≥ 9.0 g/dL
* Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT): ≤ 1.5 x upper limit of normal (ULN)
* Total bilirubin: \< 2.0 x ULN (Except for patients with Gilbert's syndrome, who must have direct bilirubin \< 2.0 x ULN)
* Aspartate aminotransferase (AST) / alanine aminotransferase (ALT): \< 3.0 x ULN
* Calculated (calc.) creatinine clearance (CrCl): ≥ 50 mL/min
* Calculated by Cockcroft-Gault equation
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done within 14 days prior to registration is required
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* No active brain metastases or leptomeningeal disease
* HIV: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* No known medical condition causing an inability to swallow oral formulations of agents
* No current symptomatic pulmonary disease
* No autoimmune disorders that require systemic treatment (except hyperthyroidism or diabetes mellitus) PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, DRUG: Lomustine, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, BIOLOGICAL: Relatlimab, PROCEDURE: Surgical Procedure
Progressive Glioblastoma, Recurrent Glioblastoma
ShortStop-HER2: 12 Months vs. 6 Months of HER2-targeted Medications for People With HER2+ Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Trastuzumab
Jack Beranek - breastprotocols@alliancenctn.org
NCT06876714
Inclusion Criteria:
* Patients (females and males) with clinical stage T1c-T3 (or Tx) and nodal stage N0-N1 (except T3N1 tumors, which are not eligible)
* Patients must have no residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy. Residual ductal carcinoma in situ (DCIS) is allowed. Patients with residual isolated tumor cells at surgery are considered node-positive and are not eligible
* HER2+ by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Central pathology review is not required. In cases where there were multiple tumor sites in breast/nodes that had HER2 testing at diagnosis, at least one site must have been HER2+ AND the treating investigator must feel it is in the patient's best interest to be treated as having HER2+ breast cancer
* Known hormone receptor status as defined by ASCO/CAP guidelines. Estrogen receptor (ER) and progesterone receptor (PR) of any values are allowed. Hormone receptor positive status can be determined by either known positive ER or known positive PR status; hormone receptor negative status must be determined by both known negative ER and known negative PR
* If invasive disease was present in both breasts, participation in the study is permitted as long as the eligibility criteria are met for both tumors/breasts (including the requirement that at least one biopsied site on each side must have been HER2+)
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Patients must have received neoadjuvant chemotherapy in combination with trastuzumab with or without pertuzumab for a minimum of 12 weeks. All chemotherapy must have been completed preoperatively
* Patient must complete a minimum of 12 weeks of coverage with trastuzumab and a maximum of 24 weeks in the combined neoadjuvant and adjuvant setting prior to trial registration. Trastuzumab may have been administered either weekly or once every 3 weeks (q3weeks). (For purposes of this eligibility criterion, a single dose of q3week trastuzumab would provide 3 weeks of coverage; a single dose of once a week (q1week) trastuzumab would provide 1 week of coverage. If a q3week dose of trastuzumab were administered and then the subsequent dose was delayed for any period of time, that would still count as 3 weeks of coverage.)
* Administration of endocrine therapy for treatment of this breast cancer is allowed prior to trial registration. If a patient received prior breast cancer endocrine therapy (eg tamoxifen or aromatase inhibitor) for DCIS or preventive indication, and endocrine therapy is indicated for treatment of their current breast cancer, then prior endocrine therapy must have been stopped \> 12 months prior to registration on this protocol
* No use of investigational anti-cancer agents at time of registration
* Patient must register within 14 weeks of final surgery
* Adequate excision: Surgical removal of all clinically evident disease in the breast and lymph nodes as follows:
* Breast surgery: Total mastectomy with grossly negative margins (in the opinion of the surgeon there is no disease grossly at the margins) or breast-conserving surgery with histologically negative margins (no ink on tumor, including DCIS) unless those margins are anterior at the skin or posterior at the chest wall and no additional margin re-excision can be performed
* Lymph node surgery: Lymph node surgery must have been performed and can include sentinel lymph node biopsy, targeted axillary dissection, or axillary dissection, at the discretion of the breast surgeon
* Adequate radiation: Patients who completed breast-conserving surgery (i.e. lumpectomy) must have received or plan to receive adjuvant radiation. If breast-conserving surgery was performed but patient will not be receiving breast radiation, the patient is not eligible. Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation) are not eligible
* Adjuvant radiation can be given on study, and in this case is encouraged to be given concurrently with adjuvant HER2-directed therapy, per investigator discretion
* Targeting of the regional nodal basins will be at treating investigator discretion
* Not pregnant and not nursing, because this study involves agents with known teratogenic potential. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test should be performed prior to receiving HER2-directed therapy according to local standard practice
* Adequate hepatic, renal and bone marrow function to receive adjuvant HER2-directed therapy in the opinion of the treating investigator. There are no specific required laboratory values for eligibility
* No stage IV (metastatic) breast cancer
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* No history of any prior (ipsilateral \[ipsi-\] or contralateral) invasive breast cancer. Prior DCIS is allowed
* No evidence of recurrent disease following preoperative therapy and surgery
* Patients living with HIV who are healthy and deemed by their medical team to have a low risk of AIDS-related illnesses are included in this trial. Patients with Hepatitis B or Hepatitis C virus who are healthy and deemed by their medical team to meet all other enrollment criteria are included in this trial.
* Patients with inadequate cardiac function on most recent assessment of left ventricular ejection fraction (LVEF) are not eligible for this trial. Inadequate cardiac function is defined as LVEF \< 50% on echocardiogram (echo) or multiple-gated acquisition (MUGA)
* No history of grade 3 or 4 toxicity related to trastuzumab. If pertuzumab is planned to be given on trial, patient must also have no history of grade 3-4 toxicity related to pertuzumab
* No contraindication to receipt of further HER2-directed therapy
* No patients with severe, uncontrolled systemic disease that may interfere with planned trial therapy.
Exclusion Criteria:
\- BIOLOGICAL: Trastuzumab (Herceptin), BIOLOGICAL: Pertuzumab, PROCEDURE: Echocardiography, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Mammography, PROCEDURE: Ultrasound, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Early Stage Breast Carcinoma
Adding the Immunotherapy Drug Cemiplimab to Usual Treatment for People With Advanced Non-Small Cell Lung Cancer Who Had Previous Treatment With Platinum Chemotherapy and Immunotherapy (An Expanded Lung-MAP Treatment Trial)
Jennifer Beeler - jbeeler@swog.org
NCT06616584
Inclusion Criteria:
* Participants must have been assigned to S1800E by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1800E is determined by the LUNGMAP protocol
* Participants must have measurable or non-measurable disease documented by CT or MRI. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to randomization. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration
* Participants must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to randomization
* Participants must have received exactly one anti-PD-1 or anti-PD-L1 therapy for advanced disease (stage IV or recurrent disease, or stage I-III disease in certain circumstances outlined below). Anti-PD-1 or anti-PD-L1 therapy may have been given alone or in combination with other therapy. For participants who received neoadjuvant, adjuvant, and/or consolidation anti-PD-1 or anti-PD-L1 therapy for stage I-III disease:
* If they experienced disease progression within (≤) 365 days from initiation (cycle 1 day 1) or anti-PD-1 or anti-PD-L1 therapy, this counts as the single allowed anti-PD-1 or anti-PD-L1 therapy for advanced disease
* If they experienced disease progression more than (\>) 365 days from initiation (cycle 1 day 1) or anti-PD-1 or anti-PD-L1 therapy, this is not considered anti-PD-1 or anti-PD-L1 therapy for advance disease. These participants must have received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease
* Participants must have experienced disease progression (in the opinion of the treating investigator) more than (\>) 84 days following initiation (cycle 1 day 1) of their most recent anti-PD-1 or anti-PD-L1 therapy
* Participants who received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease must have had a best response of stable disease, partial response or complete response (in the opinion of the treating investigator) on the anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease
* Participants must have received platinum-based chemotherapy and experienced disease progression (in the opinion of the treating investigator) during or after this regimen
* Participants with a known sensitizing molecular alteration for which a Food and Drug Administration (FDA)-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, KRAS, HER2, and MET sensitizing mutations), must have previously received at least one of the approved therapy(s). Prior targeted therapy for participants with targetable alterations is allowed if all other eligibility criteria are also met
* Participants must have recovered (≤ grade 1) from any side effects from the most recent anti-cancer treatment prior to randomization
* Participants must not have received prior therapy with docetaxel for this disease
* Participants must not have received any palliative radiation therapy within 14 days (or palliative bone radiation therapy within 7 days) prior to randomization
* Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, or biologic therapy for cancer treatment while receiving treatment on this study
* Participants must not have undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization. Participants must not have postoperative bleeding complications or wound complications from a surgical procedure performed within 2 months prior to randomization. The participant must not have elective or planned major surgery to be performed during the course of this study
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to randomization)
* Hemoglobin ≥ 9.0 g/dL (within 28 days prior to randomization)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to randomization)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to randomization) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN (within 28 days prior to randomization). Participants with history of liver metastasis must have AST and ALT ≤ 5 x ULN
* Participants must have a creatinine ≤ the institutional (I)ULN or calculated creatinine clearance ≥ 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to randomization
* Participants must have a urinary protein test performed within 28 days prior to randomization
* Participants' most recent Zubrod/Eastern Cooperative Oncology Group (ECOG) performance status must be 0-1 and be documented within 28 days prior to randomization
* Participants must have a completed medical history and physical exam within 28 days prior to randomization
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization, if indicated by the treating investigator
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization, if indicated by the treating investigator
* Participants with known human immunodeficiency virus (HIV) infection are eligible, provided they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to randomization
* Participants must not have a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not have an active autoimmune disease that has required systemic treatment within 730 days prior to randomization (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* Participants must not have any history of primary immunodeficiency
* Participants must be able to safely receive study therapy and must not have experienced the following:
* Any grade 3 or worse immune-mediated adverse event. Exception: asymptomatic nonbullous/nonexfoliative rash
* Any unresolved grade 2 immune-mediated adverse event
* Any toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1 immunotherapy
* Exception to the above: Toxicities of any grade that requires replacement therapy and has stabilized on therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) are allowed
* Participants must not have any history of organ transplant that requires use of immunosuppressives
* Participants must not have received a live or live attenuated vaccine within 28 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever rabies, Bacillus Calmette-Guerin (BCG) and typhoid vaccine. Seasonal influenza vaccines and COVID-19 vaccines are allowed, however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated and are not allowed
* Participants must not have clinical signs or symptoms of active tuberculosis infection
* Participants must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis/interstitial lung disease
* Participants must not have had a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
* Participants must not have a history of gastrointestinal perforation or fistula within 6 months prior to randomization
* Participants must not have grade 3-4 gastrointestinal bleeding (defined by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) within 3 months prior to randomization. No history of gastrointestinal (GI) bleed within 3 months prior to randomization
* Participants must not have any grade III/IV cardiac disease as defined by the New York Heart Association criteria (i.e., participants with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months prior to randomization, or serious uncontrolled cardiac arrhythmia
* Participants must not have experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to randomization
* Participants must not have gross hemoptysis within two months prior to randomization (defined as bright red blood or ≥ 1/2 teaspoon) or with radiographic evidence of intratumor cavitation or has radiologically documented evidence of major blood vessel invasion or encasement by cancer
* Participants must not have been diagnosed with venous thrombosis within 3 months prior to randomization. Participants with venous thrombosis diagnosed more than 3 months prior to randomization must be on stable doses of anticoagulants
* Participants must not have cirrhosis at a level of Child-Pugh B (or worse) AND a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis, OR any degree of cirrhosis
* Participants must not be pregnant or breastfeeding (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)
* Participants must be offered participation in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG specimen tracking system
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. NOTE: Participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations PROCEDURE: Biospecimen Collection, BIOLOGICAL: Cemiplimab, PROCEDURE: Computed Tomography, DRUG: Dexamethasone, DRUG: Docetaxel, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Ramucirumab
Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8
A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
ctrrecruit@vcu.edu
NCT06524544
Inclusion Criteria:
* Patient must be ≥ 18 years of age
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Patient must have locally advanced (unresectable or not amenable to curative intent therapy) or metastatic urothelial cancer
* Patient must have histologically proven conventional urothelial carcinoma (UC) of any urinary tract origin \[any histologic subtype except neuroendocrine (small or large cell)\] are permitted so long as tumors include ≥ 1% urothelial histology). NOTE: Pure non-urothelial histology is excluded
* Patient must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Baseline imaging must be obtained ≤ 35 days prior to randomization
* Patient must have the following prior treatment. Patient must have had progression on or after the immediate prior therapy
* Patient must have had prior exposure to anti-PD(L)1 therapy \[anti -PD(L)1 monotherapy or as a combination regimen in any disease/therapy setting for UC. Patients must have received at least 1 dose of anti-PD(L)1 therapy
* NOTE: Anti-PD(L)1 therapy does not need to be the most recent therapy received prior to enrollment on this protocol
* Patient must not have had progression within 12 weeks of using anti-PD(l) 1 therapy
* Patient must have had ≥ 1 line of systemic therapy given in the advanced/metastatic disease setting. For tumors with FGFR3 + susceptible alteration (for FGFR inhibitor), patients must have received a prior FGFR inhibitor unless contraindicated per physician discretion
* Patient must have received prior enfortumab vedotin in any disease/therapy setting unless contraindicated per physician
* Patient must have had no prior exposure to sacituzumab govitecan or other TROP-2 directed therapies or antibody-drug conjugate that contains topo-isomerase I inhibitor, e.g. trastuzumab deruxtecan
* Patient must have Bellmunt score of 0-2. The Bellmunt score assesses a patient's risk and is calculated based upon ECOG PS, the hemogloblin level and presence of liver metastases
* Patient must not have any history of grade 3 or higher immune-related adverse events on prior anti-PD1/L1, except for endocrinopathies on adequate hormone therapy repletion and clinically insignificant laboratory abnormalities
* Patient must have recovered (i.e., ≤ grade 1) from clinically significant AEs due to previously administered systemic therapy agent, except for endocrinopathies on adequate hormone therapy repletion
* NOTE: Patients with ≤ grade 2 neuropathy, any grade of alopecia, or any grade of non-clinically significant laboratory abnormality are exceptions to this criterion and are allowed in this trial.
* Examples of non-clinically significant laboratory abnormalities include, but are not limited to:
* Lymphopenia or monopenia
* Lymphocytosis or monocytosis
* Increase in amylase or lipase with no clinical correlation
* Any other abnormal laboratory findings that have no clinical relevance per the treating investigators.
* NOTE: If patient has undergone major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to randomization
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Patient must not nurse infants while on protocol treatment and for 4 months after the last dose of protocol treatment
* Patient must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Patients of childbearing potential must continue contraceptive method(s) or abstain for 6 months after the last dose of protocol treatment. Patients with partners who could become pregnant should use effective contraception during therapy and for 3 months after the last dose of protocol treatment
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Absolute neutrophil count (ANC) ≥ 1,500/uL (obtained ≤ 14 days prior to randomization)
* Platelets ≥ 100,000/uL (obtained ≤ 14 days prior to randomization)
* Albumin ≥ 3 g/dL (obtained ≤ 14 days prior to randomization)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 14 days prior to randomization)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN or ≤ 5.0 x institutional ULN if known liver metastases (obtained ≤ 14 days prior to randomization)
* Creatinine clearance (CrCl) ≥ 30 mL/min (obtained ≤ 14 days prior to randomization) NOTE: CrCl is estimated using the Cockcroft-Gault formula (or can be measured by 24-hour urine collection if needed)
* Patient must not have a known genetic UGT1A1 deficiency (Gilbert's syndrome). Patients with variant type UGT1A1\*28 allele may have increased levels of SN-38 metabolite (due to reduced SN-38 metabolism and clearance) and are at higher risk for severe adverse events when compared to wild-type.
* NOTE: If a patient's UGT1A1 status is unknown, they are eligible to enroll (the study does not require this test as part of screening)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and considered cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and are not using steroids \> 10 mg of prednisone (or equivalent) daily for brain metastases for at least 7 days prior to randomization
* Patients with a prior or concurrent malignancy that is not considered clinically significant and whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (at the discretion of the treating physician) are eligible for this trial
* Patient must not be on systemic immunosuppressive medication, including steroids (if doses exceed the equivalent of prednisone 10 mg daily). Short courses of steroids, e.g. "burst", which are discontinued prior to randomization are acceptable. Patients on inhaled, intranasal, intra-articular and/or topical steroids are eligible
* Patient must be English or Spanish speaking to be eligible for the HRQOL component of the study.
* NOTE: Sites cannot translate the associated HRQOL forms PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Docetaxel, DRUG: Gemcitabine, PROCEDURE: Magnetic Resonance Imaging, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, OTHER: Questionnaire Administration, BIOLOGICAL: Sacituzumab Govitecan
Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Unresectable Urothelial Carcinoma
Adagrasib + SRS for Patients With Metastatic KRAS G12C-mutated NSCLC With Untreated Brain Metastases
Ryan Gentzler, MD, MS - rg2uc@uvahealth.org
NCT06248606
Inclusion Criteria:
• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Confirmation of stage IV non-small cell lung cancer (NSCLC) per AJCC, 8th edition, or metastatic recurrence after treatment for earlier stage disease.
• Known to have a KRAS G12C mutation. KRAS G12C mutation can be determined based on local tissue and/or ctDNA testing.
• Presence of brain metastases that meet the following criteria: * Patients must have at least 1 untreated enhancing intracranial lesion, per local radiology interpretation, measuring at least 2mm. NOTE: intracranial lesions do not need to be measurable by RECIST 1.1 criteria to be eligible. * Must have no single metastasis measuring larger than 3 cm. * Patients with surgically resected brain metastases are eligible provided there are additional brain metastases amenable to SRS * Patients with progression of previously radiated or surgically resected CNS metastases are eligible if solid component of lesion has enlarged and there is no concern for radionecrosis based on investigator discretion. * Patients who received SRS within 4 weeks prior to registration are eligible provided baseline brain MRI prior to SRS treatment is within 4 weeks of study registration and SRS treatment meets requirements in #7 below. * Symptomatic brain metastases are permitted if the following criteria are met: * No evidence of cerebral herniation or symptomatic leptomeningeal disease * No seizures within past 14 days; antiepileptic medications are permitted * Patients on steroids must have stable or improving neurologic symptoms that have not worsened during a steroid taper. Must be receiving the equivalent of dexamethasone 8 mg total daily dose or less at the time of registration.
• CNS lesions have already been treated with SRS (within 3 weeks prior to Cycle 1 Day 1) or are amenable to SRS as determined by radiation oncologist and/or neurosurgeon. SRS treatment must use GammaKnife or linear accelerator-based treatments with nominal x-ray energy of 6MV or greater.
• No contraindications to SRS. Patients on anticoagulation must be able to hold anticoagulation for SRS treatment based on investigator discretion.
• Patients may be treatment-naïve OR have received up to 2 prior lines of systemic therapy. Treatment with systemic therapy for Stage I-III disease \> 12 months prior to development of metastases do not count as a line of therapy. Treatment with platinum-doublet chemotherapy and checkpoint inhibitor immunotherapy (PD-1, PD-L1, CTLA-4, etc.) either in combination or sequentially counts as one line of therapy.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration. * Hemoglobin (Hgb): ≥ 8.0 g/dL in the absence of transfusions within 7 days prior to testing. * Calculated creatinine clearance: ≥ 60 mL/min * Bilirubin: ≤ 1.5 mg/dL * Aspartate aminotransferase (AST): ≤ 3.0 × ULN * Alanine aminotransferase (ALT): ≤ 3.0 × ULN
• Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to treatment initiation.
• Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from heterosexual activity or to use an effective method(s) of contraception. Males able to father a child who are sexually active with female of childbearing potential must be willing to abstain from heterosexual activity or to use an effective method(s) of contraception.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial. Testing is not required at screening unless mandated by local policy.
• Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. Testing is not required at screening unless mandated by local policy.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Exclusion Criteria:
• Prior treatment with KRAS G12C tyrosine kinase inhibitor.
• Active infection requiring systemic therapy with the exception of #13 and #14 above.
• Uncontrolled, significant intercurrent or recent illness.
• Prolonged QTc interval \> 480 milliseconds or history of congenital Long QT Syndrome
• Currently receiving radiation treatment at the time of enrollment to any extra-cranial lesion for prophylaxis or pain control. Patients may enroll after completion of palliative RT.
• Ongoing need for treatment with concomitant medication known as a strong inhibitor or inducer of CYP3A enzyme and that cannot be switched to an alternative treatment prior to study enrollment. NOTE: Discontinuation of CYP3A4 inducers should occur a minimum of 7 days or 5 times their half-life, whichever is longer, prior to C1D1 study treatment.
• Treatment with any investigational drug within 28 days prior to registration.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
DRUG: Adagrasib, RADIATION: Stereotactic Radiosurgery
Non Small Cell Lung Cancer, NSCLC, KRAS G12C
A Study to Learn About a Study Medicine Called Ibuzatrelvir in Adult and Adolescent Patients With COVID-19 Who Are Not Hospitalized But Are at Risk For Severe Disease
Pfizer CT.gov Call Center - ClinicalTrials.gov_Inquiries@pfizer.com
NCT06679140
Inclusion Criteria:
• 12 to \<18 years of age, weighing at least 40 kg, or ≥18 years of age of any weight at screening.
• Presence of risk factors for progression to severe COVID-19 at the time of screening based on age:
• 12 to 49 years of age with at least two risk factors, where one must be moderate immunocompromise;
• 50 to 64 years of age with at least two risk factors;
• 65 to 74 years of age with at least one risk factor;
• For participants 75 years of age or older, there are no requirements related to risk factors. The list of risk factors includes: BMI ≥35 kg/m2; Current smoker; Chronic lung disease; Cardiovascular disease; Type 1 or Type 2 diabetes mellitus; Mild to moderate renal impairment; Neurodevelopmental disorders; Sickle cell disease; Moderate immunosuppression.
• Confirmed SARS-CoV-2 infection as determined by RAT in nasal or NP specimen collected within 1 day prior to randomization. Initial onset of symptoms attributable to COVID-19 within 5 days prior to randomization and at least 1 of the specified symptoms attributable to COVID-19 present on the day of randomization. Randomization must occur no later than the 5th day, where the onset of symptoms is the first day.
• Participants must be unable or unwilling to take nirmatrelvir/ritonavir.
Exclusion Criteria:
• Current need or anticipated need for hospitalization within 24 hours, due to signs of severe COVID-19 illness (eg, SpO2 \<94% on room air, respiratory rate \>30 breaths/minute, or lung infiltrates \>50%) or due to other medical conditions requiring hospitalization in the opinion of the site investigator.
• Receiving dialysis or have known severe renal impairment \[ie, eGFR consistently \<30 mL/min/1.73 m2 for adults or CrCl \<30 mL/min for adolescents\], using the serum creatinine-based CKD-EPI formula or the Cockroft Gault, respectively.
• Active liver disease with AST or ALT \>3 ULN, Total bilirubin ≥2 × ULN (for Gilbert's syndrome, direct bilirubin \>ULN is exclusionary) within the past 3 months, or liver function impairment with Class C per Child Pugh classification.
• Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention.
• Ongoing Long COVID or Post Acute Sequelae of COVID-19 diagnosis.
• Severely immunocompromised.
• Any comorbidity requiring hospitalization and/or surgery within 7 days prior to study entry, or that is considered life threatening within 30 days prior to study entry, as determined by the investigator.
• History of hypersensitivity or other contraindication to any of the components of the study interventions.
• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Current use of any prohibited concomitant medication(s).
• Has received any other antiviral for the treatment of COVID-19, including remdesivir, nirmatrelvir/ritonavir, molnupiravir, or COVID-19 mAbs within 30 days or 5 half-lives \[whichever is longer\] prior to screening, or received convalescent COVID-19 plasma within 12 months.
• Received any dose of a COVID-19 vaccine within 4 months of randomization or expected to receive one through Day 34.
• Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).
• Prior participation in this clinical trial or any other clinical trial of ibuzatrelvir.
• Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
DRUG: ibuzatrelvir, DRUG: placebo
COVID-19 SARS-CoV-2 Infection
Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases, COVID-19, Viral Protease Inhibitors, Protease Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antiviral Agents, Anti-Infective Agents, ibuzatrelvir
A Study to Evaluate Safety, Tolerability, and Efficacy of AB-1009 Gene Therapy (GAA Gene) in Adult Participants With Late Onset Pompe Disease (PROGRESS-GT LOPD)
AskFirst Patient Engagement - AskFirst@AskBio.com
NCT07282847
Inclusion Criteria:
• Participant must be ≥18 years of age at the time of signing the informed consent form.
• Confirmed GAA enzyme deficiency from any tissue source and/or confirmed biallelic GAA gene mutations.
• Undergone enzyme replacement treatment (ERT) (either alglucosidase alfa (Lumizyme®) or avalglucosidase alfa-ngpt (Nexviazyme®)), for at least 6 months (at least 10 infusions) before signing the initial informed consent form. During the screening process, participants need to remain on their current ERT until close to dosing;
• FVC in the upright position ≥30% and ≤80% of predicted;
• Capable of walking at least 100 meters in the 6MWT (use of a cane, quad cane, or standard walker is permitted);
• Contraceptive/barrier use by men and women requirements as per protocol.
• Capable of giving informed consent and able to understand and comply with all study procedures.
Exclusion Criteria:
• Severe cardiomyopathy, defined as left ventricular ejection fraction (LVEF) \<40% or New York Heart Association (NYHA) functional class 3 or above;
• Require invasive mechanical ventilation, or rely on noninvasive ventilation during the day;
• Intolerance to ERT or investigator-assessed intolerance to ERT, prior experience of serious ERT-related infusion-associated reactions (IARs);
• Have known intrinsic liver diseases, including hepatitis, HIV-related liver disease, prior diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy, severe fatty liver, cirrhosis or liver fibrosis ≥stage 2, ultrasound-identified liver neoplasms, or laboratory tests suggesting elevated alpha-fetoprotein. Patients with liver function tests including ALT or AST \>3× upper limit of normal (ULN) or any total bilirubin above ULN during screening will also be excluded;
• Prior or ongoing medical condition(s), physical finding(s), assessment findings, or laboratory abnormality that, in the investigator's opinion, would impact participant's safety and compliance with the study procedures.
• Have received gene therapy prior to screening;
• Have received any systemic immunosuppressants (except inhalation or topical use) other than glucocorticoids or investigator-recommended immunosuppressants 30 days prior to screening through completion of screening, and/or known intolerance to immunosuppressants such as glucocorticoids;
• Use of investigational drugs or drugs that could affect this study as evaluated by the investigator within 30 days prior to screening through completion of Week 52 or within 5 half-lives of the investigational drug (whichever is longer);
• Have received any vaccine within 30 days prior to dosing;
• Other conditions that make the participant not eligible for the study according to the investigator.
GENETIC: AB-1009 (GAA Gene)
Pompe Disease (Late-onset), Pompe Disease Late-Onset, LOPD
Pompe Disease, Glycogen Storage Disease, Lysosomal Storage Diseases, Acid Maltase Deficiency, Acid Maltase Deficiency Disease, Gene Therapy, AB-1009, Neuromuscular Disease, LOPD, Acid-Alpha Glucoside (GAA), GAA gene, Adeno-Associated Virus (AAV), Late-Onset Pompe Disease
Elucidating the Role of Cholinergic Degeneration in Cognitive Fluctuations in Lewy Body Dementia
Madison Clemons - Madison.Clemons@vcuhealth.org
NCT07284290
Inclusion Criteria:
Arm 1:
* Age range: 50 ≤ age \< 90.
* Diagnosis of dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), Parkinson disease with Mild Cognitive Impairment (PD-MCI), Mild Cognitive Impairment with Lewy bodies (MCI-LB).
* DLB participants must fulfill criteria for clinically probable DLB based on the 2017 4th consensus report of the DLB consortium.
* PDD participants must meet criteria for clinically probable PD according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease and must also meet criteria for probable PDD based on the 2007 Movement Disorders Society clinical diagnostic criteria.
* PD-MCI participants must meet criteria for clinically probable PD according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease and meet criteria for Mild Cognitive Impairment on cognitive testing at screening.
* MCI-LB participants with must meet established research criteria.
* Capacity to provide informed consent or, if unable, availability of a legally authorized representative or guardian who can provide informed consent.
* Availability of informant (for participants meeting criteria for dementia).
* Ability and willingness to comply with the study-related procedures.
* Fluent in spoken and written English (due to cognitive testing)
Exclusion Criteria:
Arm 1
* History of cognitive disorder or psychiatric disorder other than that related to dementia with Lewy bodies or Parkinson disease dementia.
* History of deep brain stimulation or any neurosurgical procedure.
* History of structural brain disease or known significant cerebrovascular disease.
* History of seizures or epilepsy and/or use of sodium channel blockers, i.e. carbamazepine, oxcarbazepine, phenytoin, topiramate, lamotrigine, felbamate, zonisamide, rufinamide, lacosamide, eslicarbazepine, and valproate.
* Greater than two alcoholic drinks per day for men and one per day for women.
* Regular use of benzodiazepines or barbiturates. (If benzodiazepines are taken as needed only, these medications cannot be taken within 5 half-lives of screening visit or between screening visit and EEG.)
* Severe dementia (based on PI assessment of subject dependence level for instrumental activities of daily living)
* Any contraindication to brain MRI.
* Any medical condition that would interfere with ability to complete all study procedures.
* Participants must not be pregnant, planning to become pregnant, or father a child for the duration of the study
Inclusion Criteria:
Arm 2 (Cholinesterase inhibitor cohort) inclusion criteria:
* Completed Aim 1.
* Clinical diagnosis of LBD (DLB or PDD) with CF.
* Not taking a cholinesterase inhibitor and has not taken a cholinesterase inhibitor in the previous 90 days.
* Ability and willingness to comply with the ChEI Cohort procedures (including galantamine administration), or a caregiver willing and able to ensure compliance.
Exclusion Criteria:
Arm 2 (Cholinesterase inhibitor cohort) exclusion criteria:
* Severe hepatic impairment.
* Renal failure.
* Significant bradycardia (\<50 bpm) at screening or history of AV block.
* Any contraindication to galantamine administration based on PI discretion.
Inclusion criteria:
Arm 3 (Healthy Controls)
* Age range: 50 ≤ age \< 90.
* Healthy controls should not have any known neurologic conditions that could interfere with study procedures or results.
* Capacity to provide informed consent or, if unable, availability of a legally authorized representative or guardian who can provide informed consent.
* Availability of informant (for participants meeting criteria for dementia).
* Ability and willingness to comply with the study-related procedures.
* Fluent in spoken and written English (due to cognitive testing).
Exclusion Criteria:
Arm 3 (Healthy Controls)
* No History of cognitive disorder or psychiatric disorder other than that related to dementia with Lewy bodies or Parkinson disease dementia.
* No History of deep brain stimulation or any neurosurgical procedure.
* No History of structural brain disease or known significant cerebrovascular disease.
* No History of seizures or epilepsy and/or use of sodium channel blockers, i.e. carbamazepine, oxcarbazepine, phenytoin, topiramate, lamotrigine, felbamate, zonisamide, rufinamide, lacosamide, eslicarbazepine, and valproate.
* Any medical condition that would interfere with ability to complete all study procedures.
* Participants must not be pregnant, planning to become pregnant, or father a child for the duration of the study PROCEDURE: Syn-One skin biopsy, DIAGNOSTIC_TEST: Multi modal MRI, DIAGNOSTIC_TEST: Assessment of dynamic EEG features over 48-hour periods across all study aims, DIAGNOSTIC_TEST: Plasma biomarkers, DRUG: Galantamine HBr extended-release 8mg capsules (8mg ER).
Dementia With Lewy Bodies, Parkinson Disease Dementia, Healthy Controls
Parkinson Disease with Mild Cognitive Impairment, Mild Cognitive Impairment with Lewy Bodies
Testing the Addition of AZD6738 (Ceralasertib) to Immunotherapy to Increase Time Without Cancer for Patients With Non-Small Cell Lung Cancer
ctrrecruit@vcu.edu
NCT06732401
Inclusion Criteria:
* STEP 0: Patient must be \>= 18 years of age
* STEP 0: Patient must have stage II to select stage IIIB (N2 but excluding N3) non-small cell lung cancer (NSCLC) of any histology using International Association for the Study of Lung Cancer (IASLC) 8th edition. Stage is assessed at time of initiating pre-operative chemo-immunotherapy
* STEP 0: Patient must fall into one of the following categories:
* Planning to undergo, be currently undergoing, or recently completed any standard of care neoadjuvant chemo-immunotherapy with plans to undergo surgical resection
* Recently completed any standard of care neoadjuvant chemo-immunotherapy AND completed surgical resection and are awaiting pCR status.
* Recently completed any standard of care neoadjuvant chemo-immunotherapy AND completed surgical resection with confirmed non-path complete response (CR) status.
NOTES:
* Patient must have completed at least 3 cycles of neoadjuvant chemo-immunotherapy before surgery in order to be eligible for Step 1 randomization.
* Patients who have completed their surgical resection prior to enrollment in step 0 registration must have their surgery date within a window that will allow initiation of EA5231 treatment (cycle 1 day 1) to commence within 4-12 weeks following surgery
* STEP 1: EA5231 CLEAR randomization for patients without a pCR post-surgery. Patient's with pCR after surgery will be offered to enroll in the SWOG study S2414 INSIGHT instead
* STEP 1: Patient must have completed R0 resection after standard of care neoadjuvant chemo-immunotherapy (minimum three cycles completed) for stage II to select stage IIIB (N2 but excluding N3) non-small cell lung cancer (NSCLC) of any histology using IASLC 8th Edition
* STEP 1: Patient must have non-pathological CR status post-surgery. The pathological CR/non-pathological CR status will be determined by local pathology using IASLC criteria and using the surgical sample tissue
* STEP 1: Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - ≤ 2 (or Karnofsky ≥ 60%)
* STEP 1: Patient must not have any known EGFR or ALK genetic alterations. Mutation negative status will be determined per local institutional practices and consistent with National Comprehensive Cancer Network (NCCN) guidelines
* STEP 1: Patient must have undergone a chest CT after surgery and within 28 days prior to step 1 randomization
* STEP 1: Patient must have recovered from clinically significant adverse events of their most recent therapy/intervention prior to step 1 randomization
* STEP 1: Patient must not have experienced a toxicity that led to the permanent discontinuation of prior immunotherapy
* STEP 1: Patient must not be receiving ongoing steroids at a dose of prednisone 10 mg or higher (or equivalent) at the time of step 1 randomization. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) are allowed
* STEP 1: Patient must not have received or have a plan to receive post-operative radiation therapy (PORT)
* STEP 1: Patient must not have a history of treatment-related pneumonitis requiring ongoing steroids or supplemental oxygen use
* STEP 1: Patient must not have a history of interstitial lung disease (ILD)
* STEP 1: Patient must not have diagnosis of ataxia telangiectasia
* STEP 1: Patient must not have history of active primary immunodeficiency
* STEP 1: Patient must not have history of allogenic organ transplantation
* STEP 1: Patient must have body weight \> 30 kg
* STEP 1: Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria:
* Has achieved menarche at some point
* Has not undergone a hysterectomy or bilateral oophorectomy
* Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* STEP 1: Patient must not expect to conceive or father children by using highly accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Patients of childbearing potential must use at least 1 highly effective method of contraception in addition to a condom and continue to use it throughout their time on protocol treatment. Male patients must use a condom plus spermicide throughout their time on while on protocol treatment. In addition, all patients must continue contraception use for at least 6 months after the last dose of protocol treatment. Patients must also not breastfeed while on protocol treatment and for at least 6 months after the last dose of protocol treatment. Patients must not donate sperm while on protocol treatment and for 6 months after the last dose of protocol treatment
* STEP 1: Patient must not donate blood while on protocol treatment
* STEP 1: Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* STEP 1: Leukocytes ≥ 3,000/mcL (these labs must be obtained ≤ 28 days prior to step 1 randomization)
* STEP 1: Hemoglobin ≥ 9.0 g/dL (these labs must be obtained ≤ 28 days prior to step 1 randomization)
* STEP 1: Absolute neutrophil count (ANC) ≥ 1,500/mcL (these labs must be obtained ≤ 28 days prior to step 1 randomization)
* STEP 1: Platelets ≥ 100,000/mcL (these labs must be obtained ≤ 28 days prior to step 1 randomization)
* STEP 1: Total bilirubin ≤ institutional upper limit of normal (ULN) (these labs must be obtained ≤ 28 days prior to step 1 randomization)
* STEP 1: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 × institutional ULN (these labs must be obtained ≤ 28 days prior to step 1 randomization)
* STEP 1: Creatinine clearance ≥ 50 mL/min (estimated using Cockcroft-Gault method or measured) (these labs must be obtained ≤ 28 days prior to step 1 randomization)
* STEP 1: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of step 1 randomization are eligible for this trial
* STEP 1: For patients with known chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* STEP 1: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* STEP 1: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* STEP 1: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* STEP 1: Patient must not have received live attenuated vaccine within 30 days prior to the step 1 randomization, while on protocol treatment and within 30 days after the last dose of durvalumab PROCEDURE: Biospecimen Collection, DRUG: Ceralasertib, PROCEDURE: Computed Tomography, BIOLOGICAL: Durvalumab, PROCEDURE: Echocardiography Test
Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8
Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients (BASECAMP)
Satellos Medical Information - medicalinfo@satellos.com
NCT07287189
Key
Inclusion Criteria:
* Has a definitive diagnosis of DMD based on documented clinical findings and prior genetic testing with a confirmed mutation in the DMD gene.
* Male DMD patients who are ambulatory and aged ≥ 7 to \< 10 years at the time of screening.
* Stable dose of systemic glucocorticoids (i.e., prednisolone, deflazacort, or vamorolone) according to the standard of care for ≥ 3 months prior to the Screening Visit and for the duration of the trial. Patients who are not receiving glucocorticosteroids are also eligible if stopped ≥ 3 months prior to the Screening Visit.
* Stable doses of prescription medicines including ACE inhibitors, β-blockers, and diuretics (excluding glucocorticosteroids) and over-the-counter medicines and/or herbal supplements for supportive care ≥ 1 month prior to the Screening Visit and for the duration of the trial.
* Participants that have previously received delandistrogene moxeparvovec (brand name Elevidys) either in a prior clinical trial or in the commercial setting \> 18 months prior to screening whose muscle function tests have stabilized or demonstrated decline ≥ 3 months prior to Screening, as determined by investigator and documented in chart notes, will be eligible.
* Participants that have previously received an exon skipper \> 6 months prior to Screening whose muscle function tests have stabilized or demonstrated decline ≥ 3 months prior to Screening, as determined by investigator and documented in chart notes, will be eligible.
* Participants receiving a stable dose of givinostat (brand name Duvyzat) for at least 18 months or longer prior to the Screening Visit will be eligible. Participants unable to tolerate givinostat who discontinued treatment before 18 months are eligible to enroll if date of last dose is ≥ 30 days from the Screening date. Givinostat should not be discontinued, if tolerated, to meet study entry criteria.
* Participants that have received prior treatment with an investigational gene therapy product (other than delandistrogene moxeparvovec) ≥ 24 months prior to the Screening Visit.
* If participating in a physical therapy/strength training regimen, must be stable for ≥ 2 months prior to the Screening Visit and for the duration of the trial.
Key Exclusion Criteria:
* Ambulatory patients expected to experience loss of ambulation within ≤ 12 months.
* Participants for whom MRI or open muscle biopsy are contraindicated.
* Evidence of significant hepatic dysfunction, defined as GLDH \> 2X upper limit of normal (ULN) at the Screening Visit.
* Impaired cardiac function defined as a left ventricular ejection fraction of \< 50% on screening cardiac assessments (echocardiogram or MRI) or evidence of symptomatic cardiomyopathy.
* A forced vital capacity \< 60% predicted at the Screening Visit.
* Ongoing participation in any other therapeutic clinical trial or follow-up study for a therapeutic intervention
* Consumption of grapefruit juice or grapefruit containing products
* Severe behavioural or cognitive problems that preclude participation in the study, in the opinion of the investigator.
Additional entry criteria will be reviewed with the clinical site investigator. DRUG: SAT-3247, DRUG: Placebo
Duchenne Muscular Dystrophy, Duchenne, DMD, Neuromuscular Diseases, Muscular Dystrophies
muscle regeneration, satellite cell, asymmetric division, dystrophin
Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/C/D Melanoma Patients (NeoDREAM)
Sheila Dakhel, PhD - sheila.dakhel@philogen.com
NCT03567889
Inclusion Criteria:
• Histologically or cytologically confirmed diagnosis of clinical stage IIIB, IIIC, and IIID (AJCC 8th edition) locoregional melanoma that is eligible for complete surgical resection of all metastases (surgically resectable).
• Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
• Prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitors, etc.) is allowed. Before enrollment in the study, a wash-out period of 6 weeks is required and toxicities from prior treatments should be resumed to Grade ≤1.
• Males or females, age ≥ 18 years.
• ECOG Performance Status/WHO Performance Status ≤ 1.
• Life expectancy of \> 24 months.
• Absolute neutrophil count \> 1.5 x 109/L.
• Hemoglobin \> 9.0 g/dL.
• Platelets \> 100 x 109/L.
• Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl).
• ALT and AST ≤ 2.5 x the upper limit of normal (ULN).
• Serum creatinine \< 1.5 x ULN.
• LDH serum level ≤ 1.5 x ULN.
• Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV (i.e. positive anti-HBsAg with not vaccination and/or positive anti-HBcAg Ab), negative serum HBV-DNA is also required.
• All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1 unless otherwise specified above.
• All women of childbearing potential (WOCBP) must have negative pregnancy test results at the screening. WOCBP must be using, from the screening to three months following the last study drug administration, highly effective contraception methods. WOCBP and effective contraception methods are defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence. Pregnancy test will be repeated at the safety visit (only WOCBP and only for patients in Arm 1).
• Male patients with WOCBP partners must agree to use simultaneously two acceptable methods of contraception (i.e. spermicidal gel plus condom) from the screening to three months following the last study drug administration.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures. Exclusion Criteria
• Uveal melanoma or mucosal melanoma
• Evidence of distant metastases at screening.
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except: cervical carcinoma in situ, curatively treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry.
• Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
• History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
• Inadequately controlled cardiac arrhythmias including atrial fibrillation.
• Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
• LVEF ≤ 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator.
• Uncontrolled hypertension.
• Ischemic peripheral vascular disease (Grade IIb-IV).
• Severe diabetic retinopathy.
• Active autoimmune disease.
• History of organ allograft or stem cell transplantation.
• Recovery from major trauma including surgery within 4 weeks prior to enrollment.
• Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product.
• Breast feeding female.
• Anti-tumor therapy (except small surgery) within 4 weeks before enrollment.
• Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before enrollment.
• Planned administration of growth factors or immunomodulatory agents within 7 days before enrollment.
• Patient requiring or taking corticosteroids or other immunosuppressant drugs on a long-term basis will be evaluated case by case with the Sponsor for inclusion/exclusion in the study. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criteria.
• Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
• Previous enrolment and randomization in the same study.
DRUG: Daromun, PROCEDURE: Surgery, DRUG: Adjuvant therapy
Melanoma Stage IIIB, Melanoma Stage IIIC, Melanoma Stage IIID
Melanoma Stage IIIB, Melanoma Stage IIIC, Melanoma Stage IIID