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The HOPE Biobank Resource (BMT CTN 2402 HOPE) (HOPE Resource)
Megan Scott - mscott@emmes.com
NCT07227155
HCT/GT Inclusion:
• Patients with a diagnosis of Aplastic Anemia (AA), hemoglobinopathies or bone marrow failure from other causes except for malignant diseases will be eligible for enrollment on this protocol:
• AA will be defined as having peripheral blood cytopenias with a hypocellular bone marrow for age and a clinical diagnosis of aplastic anemia as determined by their treating physicians.
• Hemoglobinopathies include sickle cell disease or thalassemia. Patients receiving potentially curative therapy with HCT or GT for hemoglobinopathies will be eligible for this study.
• Individuals with bone marrow failure due to clinical or molecularly diagnosed inherited bone marrow failure, inborn errors of immunity or other cause will be included.
• Patients must receive an HCT or GT for management of their underlying disease. Allogeneic transplants including all conditioning regimens, donors, and GVHD prophylaxis regimens are eligible. This study does not define how the transplant or transplant-supportive care will be performed.
• Patients or their legal guardian must consent to participate in the CIBMTR "Protocol for a Research Database for Hematopoietic Cell Transplantation and Marrow Toxic Injuries" (NCT 1166009) to allow linkage with the longitudinal clinical data collected by CIBMTR.
• All ages minorities, sexes and genders are eligible for the study, but participants must weigh at least 10 kilograms (kg) at the time of study enrollment given the volume and number of blood draws required.
• All participants or parent/legal guardian must sign an informed consent for this study. If there are questions regarding a patient's eligibility for the study, contact the Protocol Team for review and discussion by emailing bmtctn2402@emmes.com. HCT/GT Exclusion
• Patients with aplastic anemia or hemoglobinopathies who are not pursuing allogeneic HCT or GT.
• Active malignancy.
• Hematologic malignancy or therapy for a prior hematologic malignancy in the previous five 5 years.
• Weight ≤ 10.0 kg at time of study enrollment.
• Prior autologous or allogeneic transplant. Related Donor Inclusion: 1\. All related donors for eligible recipients undergoing allogeneic HCT for AA, hemoglobinopathies, or bone marrow failure as defined in the recipient eligibility criteria above are eligible. Note: HCT recipient participants will remain eligible if the related donor declines to participate in the study. Related Donor Exclusion: 1\. Donor weight ≤ 10.0 kg at time of study enrollment
• Patients with a diagnosis of Aplastic Anemia (AA), hemoglobinopathies or bone marrow failure from other causes except for malignant diseases will be eligible for enrollment on this protocol:
• AA will be defined as having peripheral blood cytopenias with a hypocellular bone marrow for age and a clinical diagnosis of aplastic anemia as determined by their treating physicians.
• Hemoglobinopathies include sickle cell disease or thalassemia. Patients receiving potentially curative therapy with HCT or GT for hemoglobinopathies will be eligible for this study.
• Individuals with bone marrow failure due to clinical or molecularly diagnosed inherited bone marrow failure, inborn errors of immunity or other cause will be included.
• Patients must receive an HCT or GT for management of their underlying disease. Allogeneic transplants including all conditioning regimens, donors, and GVHD prophylaxis regimens are eligible. This study does not define how the transplant or transplant-supportive care will be performed.
• Patients or their legal guardian must consent to participate in the CIBMTR "Protocol for a Research Database for Hematopoietic Cell Transplantation and Marrow Toxic Injuries" (NCT 1166009) to allow linkage with the longitudinal clinical data collected by CIBMTR.
• All ages minorities, sexes and genders are eligible for the study, but participants must weigh at least 10 kilograms (kg) at the time of study enrollment given the volume and number of blood draws required.
• All participants or parent/legal guardian must sign an informed consent for this study. If there are questions regarding a patient's eligibility for the study, contact the Protocol Team for review and discussion by emailing bmtctn2402@emmes.com. HCT/GT Exclusion
• Patients with aplastic anemia or hemoglobinopathies who are not pursuing allogeneic HCT or GT.
• Active malignancy.
• Hematologic malignancy or therapy for a prior hematologic malignancy in the previous five 5 years.
• Weight ≤ 10.0 kg at time of study enrollment.
• Prior autologous or allogeneic transplant. Related Donor Inclusion: 1\. All related donors for eligible recipients undergoing allogeneic HCT for AA, hemoglobinopathies, or bone marrow failure as defined in the recipient eligibility criteria above are eligible. Note: HCT recipient participants will remain eligible if the related donor declines to participate in the study. Related Donor Exclusion: 1\. Donor weight ≤ 10.0 kg at time of study enrollment
Aplastic Anemias, Hemoglobinopathies, Bone Marrow Failure
Biorepository, Biospecimens, Allogenic Transplant, Gene Therapy
Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII
Black Diamond Therapeutics Clinical Trial Navigation Service - blackdiamondtx@careboxhealth.com
NCT07326566
Key
Inclusion Criteria:
* Newly diagnosed histologically confirmed glioblastoma that is isocitrate dehydrogenase wild type (IDH-WT).
* Positive EGFR status in the brain tumor as determined by a commercially available test or validated laboratory assay (CLIA or comparable certification).
* For Part 1 (Safety Lead-in) ONLY: EGFR alterations.
* For Part 2 (Randomized, Controlled Trial) ONLY: EGFRvIII.
* For Part 2 (Randomized, Controlled Trial) ONLY: Unmethylated MGMT promoter tumor status based on a validated assay.
* No treatment for newly diagnosed GBM other than surgery followed by standard-of-care adjuvant postoperative radiation (54 to 60 Gy) and TMZ chemotherapy.
* At least 4 weeks since completion of radiation therapy, with a post-radiation MRI showing no progression.
Key Exclusion Criteria:
* Recurrent multifocal disease, metastatic, leptomeningeal, or extracranial GBM, or gliomatosis cerebri.
* Progression of GBM prior to Enrollment, Screening, or Randomization.
* Biopsy-only/no resectional surgery.
* Prior or concomitant treatment for GBM with an EGFR-targeting agent, including silevertinib, bevacizumab, cytotoxic chemotherapy, immunotherapy, experimental therapies, Gliadel wafers, GammaTile®, or other intratumoral or intracavitary antineoplastic therapy.
* Intent to use Optune® (TTF).
* Significant other uncontrolled health conditions or other malignancies. DRUG: silevertinib in combination with temozolomide, DRUG: temozolomide (TMZ)
Glioblastoma (GBM), Newly Diagnosed Glioblastoma, GBM, Glioblastoma Multiforme (GBM), Glioma, Central Nervous System Diseases, Brain Cancer
EGFR, Glioblastoma, Unmethylated, Unmethylated MGMT promoter, Newly Diagnosed, temozolomide, Temodar, silevertinib, BDTX-1535, EGFR alterations, epidermal growth factor receptor, EGFRvIII, epidermal growth factor receptor (EGFR)
A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease (INVEST-HD)
Novartis Pharmaceuticals - novartis.email@novartis.com
NCT07326709
Inclusion Criteria:
* Signed informed consents must be obtained prior to participation in the study
* Ambulatory male or female participants between 21 to 70 years of age, inclusive, on the day of Informed Consent signature
* Genetically confirmed HD diagnosis with a cytosine-adenine-guanine (CAG) repeat length of 40 or above. Participants must have prior genetic confirmation and known CAG repeat length obtained prior to screening.
* Meets all of the following criteria:
* UHDRS IS score ≥90
* UHDRS TFC score = 13
* UHDRS TMS score = 7-25, inclusive
* CAP100 ≥ 70 Calculation: CAP = Age at study entry × (CAG length - 30) / 6.49
Exclusion Criteria:
* History of gene therapy or cell transplantation or any other experimental brain surgery for the treatment of HD
* Serologic evidence for active viral hepatitis as indicated by:
* positive anti-HBc IgM
* positive anti-HBc IgG confirmed by positive HBsAg and/or HBV DNA
* positive HCV ab test confirmed by positive HCV RNA
* Immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result
* History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants such as:
* Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker
* History of familial long QT syndrome or known family history of Torsade de Pointes
* Women of childbearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral salpingectomy at least six weeks before taking study treatment. In the case of oophorectomy alone, the reproductive status of the woman needs to have been confirmed by follow-up hormone level assessment.
o WOCBP are excluded unless they are using highly effective methods of contraception (failure rate \< 1% per year) while taking study treatment and for 8 months after stopping study treatment.
* Pregnant or nursing (breastfeeding) women
Other protocol defined inclusion/exclusion criteria may apply DRUG: Votoplam (blinded), DRUG: Placebo
Huntington Disease
HD, INVEST-HD, HTT227, VOTOPLAM, HUNTINGTON DISEASE, UHDRS, mHTT, NfL
Family Communications After Genetic Testing
Rachel Wills - rwills@bsd.uchicago.edu
NCT07143487
Inclusion Criteria:
* STEP 1 PROBANDS: Age \>= 18 years
* STEP 1 PROBANDS: Patients with a newly diagnosed (within 3 months of registration), primary colorectal adenocarcinoma, stage I to IV
* Histologically proven stage I to IV colon or rectal adenocarcinoma (any T or N, M+). Tumors deemed to originate in the colon can extend into/involve the small bowel (e.g., those at the ileocecal valve). Tumors will be regarded as originating in the colon if the entire tumor is in the colon. In the case of rectal involvement, the cancer will be considered a rectal primary
* Patients with more than one primary colon adenocarcinoma are eligible
* STEP 1 PROBANDS: No patients with stage 0 or in-situ colorectal cancer
* STEP 1 PROBANDS: Patients who have had prior malignancies are eligible, including non-invasive cancers
* STEP 1 PROBANDS: Patients with synchronous second malignancies are eligible
* STEP 1 PROBANDS: Have not received germline testing in the 2 years prior to enrollment or known hereditary colon cancer syndromes
* STEP 1 PROBANDS: Patients must have at least 2 living FDRs who meet the eligibility criteria, with whom the patient is willing to share their cancer diagnosis
* STEP 1 PROBANDS: In order to complete the mandatory patient-completed measures and view the video and receive genetic education and counseling, participants must be able to speak and read English or Spanish
* STEP 1 PROBANDS: No known diagnosis of dementia or cognitive impairment. Persons with impaired decision-making capacity are ineligible as they need to be able to understand genetic test results, its implications for the patient and family, and explain genetic test results to their family members
\* No persons with a known psychiatric or documented developmental disorder that affects cognitive or emotional functions to the extent that the capacity for judgment and reason is significantly diminished, such that they cannot participate based on the judgment of the treating physician
* STEP 2 PROBANDS: Probands positive for a pathogenic germline variant (PGV) in a cancer susceptibility gene
* FDRs: Age \>= 18 years
* FDRs: Have not previously received germline genetic testing or known hereditary colon cancer syndromes
* FDRs: FDRs must reside within the United States, as genetic testing from LabCorp is only available to United States (U.S.) residents
* FDRs: In order to complete the mandatory patient-completed measures, participants must be able to speak and read English or Spanish
Exclusion Criteria:
\- PROCEDURE: Biospecimen Collection, OTHER: Genetic Testing, OTHER: Communication Intervention, OTHER: Survey Administration
Colon Adenocarcinoma, Colorectal Adenocarcinoma, Rectal Adenocarcinoma, Stage I Colon Cancer AJCC v8, Stage I Colorectal Cancer AJCC v8, Stage I Rectal Cancer AJCC v8, Stage II Colon Cancer AJCC v8, Stage II Colorectal Cancer AJCC v8, Stage II Rectal Cancer AJCC v8, Stage III Colon Cancer AJCC v8, Stage III Colorectal Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Stage IV Colon Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IV Rectal Cancer AJCC v8
Multi-site Study of the Clinical Impact of an AI-assisted Approach to Referring Patients With Interstitial Lung Disease for Diagnostic Evaluation of Pulmonary Hypertension (MOMENTOUS)
Momentous Study - momentous-study@tempus.com
NCT06911632
Inclusion Criteria:
* 18 years or older at the time of consent
* A known diagnosis of interstitial lung disease
* Diffusing capacity for carbon monoxide (DLCO) \<30% predicted, collected within 6 months prior to consent
* Willing and able to provide informed consent and undergo all study-specific procedures, including echo and RHC, if required
Exclusion Criteria:
* A known diagnosis of pulmonary hypertension (including patients prescribed a therapy specifically for pulmonary arterial hypertension (PAH))
* A RHC was completed within the previous 1 year or ordered and not yet completed at the time of consent
* LV ejection fraction ≤ 40% on most recent echo or cardiac MRI, if available
* Unclassifiable Tempus PH ECG risk result after up to 2 ECG acquisitions
* A contraindication to RHC exists (for example, pregnancy or mechanical right heart valve)
* Physician decision that if a patient is directed to RHC by the study protocol, the potential risks of RHC outweigh the potential benefits
* There is a severe concomitant illness limiting life expectancy to less than 6 months (at the discretion of the investigator)
* There is a medical or social factor that makes the patient a poor candidate for the study and/or unlikely to be able to comply with the study protocol or complete study procedures (at the discretion of the investigator) DEVICE: ECG-based AI Device - Results Returned to Investigator, PROCEDURE: Echocardiogram and Right Heart Catheterization, DEVICE: ECG-based AI Device - Results Not Returned to Investigator
Pulmonary Hypertension, Interstitial Lung Disease (ILD)
Pulmonary Hypertension, Interstitial lung disease (ILD)
A Double-blind, Randomized Controlled Trial to Investigate the Efficacy, Safety, and Pharmacokinetics of Pegloticase Administration Via Subcutaneous and Intravenous Routes Both With Methotrexate in Participants With Uncontrolled Gout
Amgen Call Center - medinfo@amgen.com
NCT07388498
Inclusion Criteria
* Participant has provided informed consent before initiation of any trial-specific activities/procedures.
* Age ≥ 18 years or ≥ legal age within the country if it is older than 18 years.
* Participants willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
* Participants with uncontrolled gout, as meeting the protocol defined criteria.
Exclusion Criteria
* Glucose-6-phosphate dehydrogenase deficiency (tested at the screening visit).
* Liver transaminase levels (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\]) \> 1.25 x upper limit of normal (ULN) or albumin \< the lower limit of normal (LLN) at the screening visit.
* Uncontrolled diabetes mellitus and/or hemoglobin A1c (HbA1c) \> 8%.
* Known intolerance to MTX.
* Participant received prior treatment with pegloticase, another recombinant uricase (ie, rasburicase or pegadricase), or concomitant therapy with a polyethylene glycol (PEG)-conjugated drug.
* A known intolerance to all protocol standard gout flare prophylaxis regimens (ie, participant must be able to tolerate at least 1 of the following: colchicine and/or non-steroidal anti-inflammatory drug and/or low-dose prednisone ≤ 10 mg/day or equivalent dose of other corticosteroid).
* Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculations \< 40 mL/min/1.73 m\^2 or currently on dialysis.
DRUG: Pegloticase, DRUG: Methotrexate
Uncontrolled Gout
Uncontrolled Gout, Pegloticase, KRYSTEXXA, Kadence
Efficacy, Safety, and Pharmacokinetics of Tirzepatide (LY3298176) Once Weekly Versus Placebo in Pediatric Participants 6 to Less Than 12 Years of Age Who Have Obesity (ADVANCE-SURMOUNT-KIDS)
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or - LillyTrials@Lilly.com
NCT07817875
Inclusion Criteria:
J4M-MC-PW02
* Are 6 to less than 12 years of age (Tanner stage 1 to 5 inclusive)
* Have:
* a body weight of ≥ 40 kilograms (kg) (88 pounds), and
* been diagnosed with obesity, as defined by BMI equal to or above the 95th percentile for age and sex, on age- and sex-specific growth chart
J4M-MC-PWMP
* Have a history of at least 1 unsuccessful effort to lose sufficient body weight after participation in a structured lifestyle modification program (diet and exercise counseling for at least 3 months) prior to screening.
* Obesity as defined by BMI equal to or above the 95th percentile for age and sex (on age- and gender-specific growth chart \[CDC-NCHS, 2022\])
Exclusion Criteria:
J4M-MC-PW02
* Have a history of
* proliferative diabetic retinopathy
* diabetic macular edema, or
* nonproliferative diabetic retinopathy that requires acute treatment
J4M-MC-PWMP
* Have undergone or plan to undergo weight reduction procedure during the study, such as, but not limited to:
* gastric bypass
* sleeve gastrectomy
* restrictive bariatric surgery, such as Lap-Band® gastric banding, or
* any other procedure intended to result in weight reduction.
* Have a diagnosis that is a secondary cause of obesity or have a history of abrupt onset of obesity suggesting a secondary cause, such as hypothalamic, monogenetic, syndromic, or endocrine causes.
* Have type 1 diabetes or history of ketoacidosis, or hyperosmolar state.
* Have HbA1c \>9.0% (75 mmol/mol) as measured by central laboratory at screening.
* Have a family or personal history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome Type 2. DRUG: Tirzepatide, DRUG: Placebo
Obesity
Pediatric, Children
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
ctrrecruit@vcu.edu
NCT07391774
Inclusion Criteria:
* STEP 0: Patient must be ≥ 18 years of age
* STEP 0: Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 28 days prior to Step 0 pre-registration
* STEP 0: Patient must be a postmenopausal woman or a man
* NOTE: Menopause can be determined by any of the following:
* Prior bilateral oophorectomy
* Age ≥ 60 years
* Age \< 60 years with amenorrhea for ≥ 12 months and estradiol and follicle stimulating hormone (FSH) levels in the postmenopausal range
* NOTE: FSH and estradiol levels should be repeated as clinically indicated to ensure menopausal status in patients with breast cancer with chemotherapy-induced amenorrhea
* STEP 0: Patient must meet one of the following staging criteria postoperatively according to American Joint Committee on Cancer (AJCC) 8th edition criteria
* pT0-T3 with 3 positive ipsilateral lymph nodes (micro-or macrometastatic disease) and no planned axillary lymph node dissection after definitive surgery in the breast and axilla with curative intent.
* pT0-T3 with N2 or N3
* pT3 with N0-N3
* NOTES:
* Patients with T4 breast cancer are not eligible.
* Positive isolated tumor cells (ITCs) in axillary nodes without micro- or macrometastasis are considered N0 for eligibility purposes.
* ITC does not contribute to nodal count for staging purposes
* STEP 0: Patient must have a primary breast tumor that is estrogen receptor (ER) positive with \> 10% ER expression by immunohistochemistry (IHC) as per 2020 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Estrogen Receptor Testing Guideline.
* NOTE: ER 1-10% are reported as ER low positive. These tumors have less endocrine-sensitive disease and are not eligible)
* STEP 0: Patient must have a primary breast tumor that is HER2-negative by current ASCO/CAP guidelines utilizing immunohistochemistry and/or fluorescence in situ hybridization (FISH)
* STEP 0: Patient may have multicentric or multifocal breast cancer if the highest stage tumor meets eligibility criteria outlined above, and the tumor sites are felt to represent a single disease process by local pathology or other sites of disease are also ER-positive (\> 10%) and HER2 negative, if such testing is completed. If local pathology feels that multicentric or multifocal disease may represent distinct disease processes repeat disease receptor testing is required other sites of disease must also be also ER-positive (\> 10%) and HER2-negative
* STEP 0: For patients who have undergone a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection
* STEP 0: For patients who have undergone mastectomy, the margins must be free of residual gross tumor. Patients with microscopic positive margins are eligible if post-mastectomy radiation treatment (RT) of the chest wall will be administered
* STEP 0: Patient must have undergone axillary staging with sentinel lymph node biopsy (SLNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND)
* STEP 0: Patient must have no evidence of locoregional or distant metastatic disease by clinical history and physical exam. Treating physician can consider additional imaging evaluation per National Comprehensive Cancer Network (NCCN) guidelines and/or institutional practice
* STEP 0: Patient must be able to have Oncotype DX testing performed.
* If Oncotype DX testing was previously performed, the results of Recurrence Score (RS) must be available and must meet Step 1 eligibility criteria.
* If Oncotype DX testing was not performed yet, tissue from the core, excisional biopsy or surgical specimen of the tumor lesion must be available and must be shipped to Exact Sciences for determination of the Oncotype DX Recurrence Score (RS) for eligibility and stratification.
* NOTE: Exact Sciences will notify the submitting institution of Recurrence Score results within two (2) weeks of receipt of the tumor specimen. Institutions will receive an email notification of eligibility status once Recurrence Score results are entered into Rave by the submitting institution
* STEP 0: Patient must have had their final cancer surgery for breast cancer (including re-excision of margins) less than 16 weeks prior to Step 0 Pre-Registration.
* NOTE: This excludes additional surgery for reconstructive purposes
* STEP 0: 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 0: Patients with synchronous DCIS or LCIS are eligible
* STEP 0: Patient with prior history of ER-negative DCIS diagnosed at least 5 years prior to Step 0 Pre-Registration without evidence of recurrence are eligible
* STEP 0: Patient must not have a prior history of invasive ER-positive breast cancer. Patients with a history of ER-negative breast cancer are eligible if they were diagnosed at least 5 years prior to Step 0 Pre-Registration and have had no evidence of recurrence
* STEP 0: Patients must not have received prior endocrine therapy such as tamoxifen, raloxifene, or aromatase inhibitors for chemoprevention within 5 years prior to Step 0 Pre-Registration with the exception of a short course of endocrine therapy of less than 6 weeks duration prior to Step 0 Pre-Registration.
* NOTE: The Oncotype DX for study eligibility must be performed on specimen obtained prior to initiation of any endocrine therapy
* STEP 0: Patient must not be concurrently using systemic hormone replacement therapy (HRT). If receiving HRT at the time of breast cancer diagnosis, this must be discontinued prior to Step 0 Pre-Registration with appropriate washout
* STEP 0: Absolute neutrophil count (ANC) ≥ 1,500/µL (obtained ≤ 28 days prior to Step 0 Pre-Registration)
* STEP 0: Hemoglobin ≥ 9.0 g/dL (obtained ≤ 28 days prior to Step 0 Pre-Registration)
* STEP 0: Platelets ≥ 100,000/µL (obtained ≤ 28 days prior to Step 0 Pre-Registration)
* STEP 0: Total bilirubin ≤ institutional upper limit of normal (ULN) or \< 1.5 x ULN for patients who have a bilirubin elevation in patients with well documented Gilbert's disease or similar syndrome involving slow conjugation of bilirubin (obtained ≤ 28 days prior to Step 0 Pre-Registration)
* STEP 0: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × institutional ULN (obtained ≤ 28 days prior to Step 0 Pre-Registration)
* STEP 0: Estimated glomerular filtration rate (eGFR) ≥ 30 mL/minute/1.73 m\^2 (obtained ≤ 28 days prior to Step 0 Pre-Registration)
* STEP 0: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 0 Pre-Registration are eligible for this trial
* STEP 0: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* STEP 0: 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 0: 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 2 or better
* STEP 0: Patient must have a standard 12-lead electrocardiogram (ECG) within 28 days prior to Step 0 Pre-Registration, documenting:
* QT interval using Fridericia's correction (QTcF) \< 450 msec.
* Resting heart rate 50-90 beats per minute (determined from the ECG)
* STEP 0: 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 0: Patient must not have comorbidities considered a safety risk for standard adjuvant chemotherapy, endocrine therapy or CDK4/6 inhibitor as per Investigator's discretion
* STEP 0: Patient must not have a contraindication to adjuvant chemotherapy based on treating physician's discretion
* STEP 0: Patient must not have received prior chemotherapy for this malignancy
* STEP 0: Patient must not have received prior CDK4/6 inhibitor
* STEP 0: Patient must not have a known contraindication to ribociclib per current Food and Drug Administration (FDA) indication
* STEP 0: Patient must not have a known hypersensitivity to any of the excipients of ribociclib and/or endocrine therapy (ET) (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy)
* STEP 0: Males must not expect to father children and males and their partners must be willing to use highly effective methods of contraception while on protocol treatment. Males must not donate sperm while on protocol treatment and for at least 12 weeks following the last dose of protocol treatment.
Highly effective methods include the following:
* Intrauterine device
* Bilateral tubal occlusion
* Vasectomized partner
* Sexual abstinence If the highly effective contraceptive methods are contraindicated or strictly declined by the patient, or in the event of sexual activity of low frequency, a combination of male condom with cap, diaphragm, or sponge with spermicide (double-barrier methods) is also considered an acceptable birth control method. Local regulation/guidelines are to be followed with regard to highly effective birth control method, if more restrictive
* STEP 1: Patient must meet all Step 0 Pre-Registration eligibility criteria at the time of their Step 1 randomization
* STEP 1: Patient must not have had any major surgery or radiotherapy within 14 days prior to Step 1 randomization
* STEP 1: Patient must have a Recurrence Score (RS) of 0-25 from Oncotype DX testing from diagnostic biopsy or surgical specimen as reported by the Exact Sciences assay DRUG: Anastrozole, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Chemotherapy, PROCEDURE: Computed Tomography, DRUG: Exemestane, DRUG: Letrozole, PROCEDURE: Oncotype DX Breast Cancer Assay, PROCEDURE: Positron Emission Tomography, DRUG: Ribociclib Succinate
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Estrogen Receptor-Positive Breast Carcinoma, HER2-Negative Breast Carcinoma
The Progressive Supranuclear Palsy Clinical Trial Platform (PTP)
PSP Trial Platform Team - psptrialplatform@ucsf.edu
NCT07173803
Inclusion Criteria:
• Clinical diagnosis of possible or probable PSP Richardson's Syndrome as defined by the 2017 Movement Disorder Society (MDS) criteria.
• Presence of PSP symptoms for ≤5 years at screening (based on the best judgment of the site PI).
• Mini-Mental State Examination (MMSE) score at screening of ≥25.
• Able to walk at least 10 steps with minimal assistance (e.g., one arm for safety, but not postural support).
• Stable doses of permitted medications as described per protocol for 30 days prior to screening.
• Resides at home or in the community (assisted living is acceptable).
• As assessed by the site PI, participant is likely to be able to comply with the protocol for the duration of the study, and has adequate vision, hearing (hearing aid permitted), and literacy (English or Spanish) sufficient for compliance with the required testing procedures.
Exclusion Criteria:
• Females who are breastfeeding or pregnant (as documented by a urine pregnancy test) during screening, or plan to become pregnant during the study.
• Females of childbearing potential who did not use a highly effective method of contraception within 28 days of screening and/or are not willing to use a highly effective method of contraception for the duration of their participation in the study.
• Lacks good venous access such that multiple blood draws would be precluded.
• Weighs less than 40kg, or more than 136kg at screening.
• Blood transfusion within 4 weeks of screening.
• Contraindications to MRI studies, including metal (ferromagnetic) implants, a cardiac pacemaker that is not compatible with MRI, and/or severe claustrophobia.
• Screening MRI scan showing structural evidence of alternative pathology not consistent with PSP that could explain a substantial portion of the participant's symptoms as indicated by the central MRI read.
• Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of study drug (e.g., clinically significant reduction in serum B12 or folate levels, clinically significant abnormalities of thyroid function, stroke, or other cerebrovascular or cardiovascular conditions), as per the site PI's judgment.
• History of severe allergic reaction (e.g., anaphylaxis) including but not limited to: severe allergic reaction to previous vaccines, foods, and/or medications.
• Hospitalization within 30 days prior to screening or baseline.
• Infections or major surgical procedures within 3 months prior to screening, judged to be clinically significant by the site PI.
• Myocardial infarction within 1 year prior to baseline, unstable angina pectoris, symptomatic congestive heart failure.
• History of cancer within the past 5 years other than treated skin squamous cell carcinoma, basal cell carcinoma, and melanoma in-situ, localized prostate cancer not requiring treatment, or prostate or breast cancer, which have been fully removed and are considered cured.
• History or presence of immunological or inflammatory conditions, including neurological disorders, meningitis or meningoencephalitis.
• History or presence of epilepsy requiring ongoing use of antiepileptic medications. Antiepileptic medications are permitted for pain or psychiatric use per the protocol.
• DSM-5 criteria for drug or alcohol abuse or dependence currently met within the past 5 years.
• Clinically significant abnormal vital signs including sustained sitting blood pressure \>160/100 mm Hg.
• Diabetes mellitus with hemoglobin A1c (HbA1c) levels of ≥8.0%.
• Known history of human immunodeficiency virus (HIV-1 or 2).
• Known history of acute/chronic hepatitis B or C unless treated curatively.
BIOLOGICAL: AADvac1, DRUG: LM11A-31
Progressive Supranuclear Palsy(PSP)
PSP, Placebo-Controlled, Double-Blind, Master Protocol
Open-label Feasibility Trial of HD-tDCS During Cognitive Behavioral Therapy for Cocaine Use Disorder
Brooke Moorman - dneurolab@vcu.edu
NCT07829263
Inclusion Criteria
* Between 18 and 65 years-of-age.
* Meet current DSM-5 criteria for Cocaine Use Disorder (CocUD), moderate or severe
* Professed interest in CocUD treatment or reducing cocaine use.
* Understand and comply with study procedures
* Positive urine result for cocaine metabolite in at least one screening visit.
Exclusion Criteria
* Current DSM-5 diagnosis of any non-cocaine substance use disorder (SUD) other than alcohol use disorder-mild or cannabis use disorder-mild
* Epilepsy or a history of multiple seizures
* Taking any medications known to reduce seizure threshold
* History of migraines, ringing in the ears, and/or a head injury that resulted in a diagnosis of concussion and/or loss of consciousness
* Current scalp condition (e.g. psoriasis) or head wound that has not completely healed
* Currently pregnant or hoping to become pregnant at any point during the study
* Significant current suicidal or homicidal ideation
* Metal plate in skull or other embedded metal fragments in body or other bodily metal
* Claustrophobia or other MRI contraindications
* Fitted with electrical implants such as pacemaker
* Present with clinically significant symptoms of acute cocaine or opioid withdrawal (these individuals would be rescheduled after resolution of acute withdrawal, if possible).
DEVICE: High Definition Transcranial Direct Current Stimulation
Cocaine Use Disorder
Transcranial Direct Current, Cognitive Behavioral Therapy
The Role of Visual Attention and Environmental Complexity in Real-world Mobility for People With Lower Limb Amputation
Paul Kline - klinep@vcu.edu
NCT07831707
Inclusion Criteria:
* unilateral transtibial LLA of either dysvascular (diabetes, peripheral vascular disease, and/or infection) or traumatic etiology
* 18 years old minimum
* able to ambulate 2 minutes without rest
* 9 months since LLA
* fitted with terminal prosthesis
* 20/60 vision or better (with or without glasses/contacts)
Exclusion Criteria:
* congenital or cancer-related LLA
* ankle-level or above LLA on the contralateral limb
* residual limb wound or contralateral foot ulcer
* unstable heart condition (including unstable angina, uncontrolled cardiac dysrhythmia, acute myocarditis, hypertension, and acute pericarditis)
* acute systemic infection
* prisoner
* inability to follow a 3-step command
* concussion/brain injury in the past 12 months
* active cancer treatment
* preexisting neurological condition (i.e., multiple sclerosis, Parkinson's disease)
* participating in prosthetic rehabilitation
* color-blindness
* history of seizure(s)
* inability to read and communicate in English.
Participants in the control group must meet the non-amputation-related criteria noted above, be within ±2 years and the same biological sex as their paired participants with LLA. OTHER: Comprehensive assessment of walking patterns and functional mobility, OTHER: Comprehensive assessment of eye movements during walking, OTHER: Questionnaire Assessments completed
Lower Limb Amputation
An Open-Label Pilot Study of VTX2735 in Recurrent Pericarditis
Ventyx Clinical Trial Contact - ClinicalTrials@ventyxbio.com
NCT06836232
Inclusion Criteria:
* Participants are male or female ≥ 18 years up to ≤ 75 years of age.
* Capable of giving signed informed consent and able to comply with the protocol
* Previously had an index (first) episode of pericarditis which met the criteria for an acute pericarditis event
* Ongoing symptomatic episode of pericarditis, or may have an episode of recurrent pericarditis in the next 4 weeks.
* CRP by local laboratory assessment prior to first dose of study treatment (participants with CRP ≤ 10 mg/L must be receiving corticosteroid treatment for RP and have evidence of pericardial inflammation)
* Pericarditis pain score ≥ 4 based on the 11-point NRS.
* Stable doses of NSAIDs, colchicine, and/or oral corticosteroids (if receiving these treatments)
Exclusion Criteria:
* Current or prior diagnosis of pericarditis that is secondary to specific prohibited causes, including but not limited to tuberculosis, blunt trauma, tumor, myocarditis, or systemic autoimmune diseases.
* History of clinically significant immunosuppressive disorder, autoimmune/autoinflammatory disorder, or primary or secondary immunodeficiency.
* Clinically important history of a medical disorder that would compromise safety or data quality, per the Investigator's judgment. DRUG: VTX2735, DRUG: VTX2735, DRUG: VTX2735, DRUG: VTX2735, DRUG: VTX2735
Recurrent Pericarditis
Ventyx, Zomagen, Recurrent Pericarditis, VTX2735, NLRP3 Inhibitor, NLRP3, Inflammasome
The Value of a Simple Tool for the Early Detection of Decompensated Heart Failure in People Over 55 on Réunion Island: A Preliminary Study in Hospitals (DEPIST'IC-RUN) (DEPIST'IC-RUN)
Jérôme CORRE, Dr - jerome.corre@chu-reunion.fr
NCT07673562
Inclusion Criteria:
Patients:
* Aged 55 and older
* Admitted on an unscheduled basis to the cardiology department at the CHU (North and South campuses) and the CHOR for any reason (in general wards or intensive care)
* Residents of Réunion
* Able to read and write French
* Enrolled in a social security program
* Willing to participate in the study
Exclusion Criteria:
Patients:
* Who cannot communicate in French
* For whom it is impossible to administer the questionnaire
* For whom the ETT and/or cardiology consultation are impossible
* Who are under guardianship, conservatorship, or judicial protection DIAGNOSTIC_TEST: Early Detection Questionnaire
Heart Failure
Decompensated heart failure, early detection, questionnaire
Comparing the Effectiveness of Less Invasive Procedures With the Current Standard of Care for the Treatment of Older Adults With Early-Stage Melanoma
ctrrecruit@vcu.edu
NCT07068074
Inclusion Criteria:
* Patient must be ≥ 75 years of age.
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* 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.
* Patient must have newly diagnosed primary cutaneous melanoma with wide local excision (WLE) and sentinel lymph node (SLN) biopsy indicated per the treating physician, pending definitive surgical management.
* NOTE: For WLE and SLN to be indicated, the patient must have either:
* Pathologic features that include ≧ Breslow 0.8 mm OR Breslow \< 0.8 mm determined at initial biopsy, with a positive margin, ulceration, lymphovascular invasion, perineural invasion or \> 1 mitosis/mm\^2.
OR
* Risk of SLN metastasis of at least 5%, as calculated using the Melanoma Institute of Australia (MIA) Sentinel Node Metastasis Prediction Tool.
* Patient must be eligible for WLE and SLN biopsy. Patients for whom SLN biopsy would be contraindicated, difficult to perform (i.e., after prior surgery in the draining basin) or impossible (i.e., after prior lymphadenectomy for another cause) are not eligible.
* Patient must be eligible for surgery and not have uncontrolled medical condition that in the opinion of the medical or surgical oncologist precludes surgical management.
* Patient must not have an active infection that precludes enrollment to this study in opinion of treating investigator.
* 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.
* 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.
* 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.
* Patient must be English speaking to be eligible for this study in order to complete the patient-reported outcomes (PROs).
* NOTE: Sites cannot translate the associated quality of life (QOL) forms. PROCEDURE: Adjuvant Therapy, OTHER: Comprehensive Geriatric Assessment, PROCEDURE: Computed Tomography, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, PROCEDURE: Sentinel Lymph Node Biopsy, BEHAVIORAL: Surveillance, PROCEDURE: Ultrasound Imaging, PROCEDURE: Wide Local Excision
Cutaneous Melanoma
A Study to Learn About the Study Medicine Called PF-08046054/SGN-PDL1V Versus Docetaxel in Adult Participants With Previously-Treated Programmed Cell Death Ligand 1 (PD-L1) Positive Non-Small-Cell Lung Cancer (NSCLC)
Pfizer CT.gov Call Center - ClinicalTrials.gov_Inquiries@pfizer.com
NCT07144280
Inclusion Criteria
* Histologically or cytologically confirmed diagnosis of NSCLC with locally advanced, unresectable Stage IIIB or IIIC not eligible for definitive chemoradiotherapy or metastatic (Stage IV: M1a, M1b, or M1c) disease per the American Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Union for International Cancer Control (UICC) Staging System. Note: Participants with a neuroendocrine component or histology are not eligible.
* PD-L1 expression on ≥1% of tumor cells based on local immunohistochemistry (IHC) testing with an assay utilizing the anti-PD-L1 monoclonal antibody clones 22C3 or SP263.
* Participants who have NSCLC with known AGAs are permitted.
* Able to provide any of the following tumor tissues for biomarker analysis:
* Archival specimen (preferably collected within 12 months after the last anticancer therapy) (see laboratory manual for details); or
* De novo biopsy from a tumor lesion, if medically feasible.
* Participants must have received the following therapies and progressed during or relapsed after receiving their most recent prior therapy, or have been intolerant to their most recent therapy:
Participants with no known AGAs must fulfill 1 of the following conditions:
* Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, and unless contraindicated, a PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).
* Experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting and received a PD-(L)1 monoclonal antibody at any time during the course of treatment.
Participants with known AGAs (eg, EGFR mutations, ALK translocations, or other relevant actionable mutations) must fulfill the following conditions:
* Must have received at least 1 relevant AGA-targeted therapy if locally available and, in the opinion of the investigator, additional AGA-targeted therapy is not in the best interest of the participant
* Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, or experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting.
* May have received PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).
Exclusion Criteria
* History of another malignancy within 3 years before the first dose of PF-08046054, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival \[OS\] ≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
* Any central nervous system (CNS) lesions, unless definitively treated with CNS-directed local therapy (surgery and/or radiotherapy). Participants with definitively treated brain metastases are eligible if they meet the following criteria:
* The participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least \>14 days prior to randomization (if requiring steroid treatment).
* No clinical or radiographic progression in the CNS following CNS-directed definitive radiotherapy and/or surgery.
* Time since CNS-directed treatment is ≥28 days prior to randomization.
* Participants with a history of leptomeningeal metastasis are excluded.
* Prior treatment with an anti-PD-L1 agent (where indicated per protocol) within 5 half-lives.
* Previous receipt of an MMAE-containing agent or prior docetaxel.
There are additional inclusion and exclusion criteria. The study center will determine if criteria for participations are met.
DRUG: PF-08046054, DRUG: Docetaxel monotherapy
Non-small Cell Carcinoma, Non-Small Cell Lung Cancer Metastatic, Non-Small Cell Lung Carcinoma
Non-small cell lung cancer NSCLC, NSCLC
Autonomic and Renal Contributions to Hypertension With ADT (ARCH)
Matthew Babcock, PhD - babcockmc@vcu.edu
NCT07848828
Inclusion Criteria:
* age 40+ years;
* resting blood pressure \<140/90 mmHg;
* fasted blood glucose \<126 mg/dL;
* testosterone ≥400 ng/dL;
* sedentary to recreationally active;
* nonsmokers;
* healthy as determined by medical history, physical exam, blood and urine chemistries and resting and exercise ECG during a physician supervised graded exercise treadmill test OR recent diagnosis of non-metastatic prostate cancer with plans to undergo androgen deprivation therapy;
* PSA \<4.00 ng/dL if in the non-cancer group;
* Gleason Score ≤7 if in the prostate cancer group;
* no use of medications that might influence cardiovascular function (e.g., antihypertensives, lipid-lowering medications);
* willing and able to be on GnRHagonist and AR inhibitor;
* not taking antioxidant vitamins, corticosteroids, or anti-inflammatory medications, or willing to stop use for four weeks prior to the start of the study;
* not using exogenous sex hormones for at least one year
Exclusion Criteria:
* -acute liver disease;
* chronic kidney disease, serum creatinine \>1.3 mg/dL, macroalbuminuria \>300 mg/g of proteinuria
* pre-existing or active cardiac, renal or hepatic disease, epilepsy or other seizure disorder;
* diabetes, active or chronic infection, disease that affects the nervous system;
* Gleason Score ≥8;
* thyroid dysfunction, defined as ultrasensitive TSH \<0.5 or \>5.0 mU/L, volunteers with abnormal TSH values will be re-considered for participation after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement;
* tobacco use within the previous 12 months DRUG: Gonadotropin Releasing Hormone Agonists (GNRH), DRUG: Androgen receptor (AR) inhibitor, DRUG: Placebo
Androgen Deprivation Therapy, Prostate Cancer, Hypertension, Autonomic Dysfunction, Renal Disease
A Study to Assess How Well and Safely Elafibranor Works in Adult Participants With Primary Sclerosing Cholangitis (ELASCOPE)
Ipsen Clinical Study Enquiries - clinical.trials@ipsen.com
NCT07387549
Inclusion Criteria:
* Adults participants aged 18 years or older
* Confirmed diagnosis of primary sclerosing cholangitis based on standard clinical, biochemical, and imaging criteria
* Compensated liver disease at screening
* Stable background therapy, where applicable prior to study entry
* Women of childbearing potential have to apply during the entire duration of the study a highly effective method of birth control
* Ability to provide written informed consent and comply with study procedures.
Exclusion Criteria:
\- History or presence of other concomitant chronic liver disease
\- History of hepatic decompensation, including: i) History of liver transplantation, current MELD 3.0 score ≥12 due to hepatic impairment.
ii) Evidence of complications of cirrhosis
* Participants with cirrhosis who are also classified as Child-Pugh B or C based on the Child Pugh score.
* History of biliary intervention within 60 days prior to the screening period, and/or presence of percutaneous drain or bile duct stent at SV.
* History of bacterial cholangitis, and/or participant on antibiotics for prophylaxis of recurrent cholangitis within 60 days prior to the SV.
* History or any current suspicion of cholangiocarcinoma or hepatocellular carcinoma
* Known malignancy or history of malignancy within the last 5 years, with the exception of local, successfully treated basal cell carcinoma or in-situ carcinoma of the uterine cervix.
* Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).
* Administration of the following medications are prohibited as specified below:
i) 3 months prior to baseline: norucholic acid, fibrates, seladelpar and glitazones.
ii) 3 months prior to baseline: cyclosporine, mycophenolate, pentoxifylline, and chronic systemic corticosteroids (except as part of management of IBD at an ongoing stable dose); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin).
* Participants who are currently participating in, plan to participate in, or have participated in an investigational drug or medical device study containing active substance within 30 days or five half-lives, whichever is longer, prior to the SV. - Participants with previous exposure to elafibranor.
* Electrocardiogram (ECG) with QT interval corrected by Fridericia's formula (QTcF) \>450 msec in males or QTcF \>470 msec in females for participants without bundle branch block.
* Significant renal disease,
* For female participants: known pregnancy, or has a positive serum pregnancy test, or lactating.
* Regular alcohol intake in excess of the recommended limit of 2 standard drinks per day for men or 1 standard drink per day for women
* History of alcohol abuse, or other substance abuse within 1 year prior to SV.
* Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in the study.
* Mental instability or incompetence
* Participant has or is known to have tested positive for human immunodeficiency virus (HIV) type 1 or 2 at SV.
* Medical conditions that may diminish life expectancy to \<2 years. DRUG: Elafibranor, OTHER: Placebo
Primary Sclerosing Cholangitis
Testing the Addition of Anti-Cancer Drug Sonrotoclax, to the Standard Treatment Zanubrutinib, for Previously Untreated CLL/SLL
Jayke Giese - leukemiaprotocols@alliancenctn.org
NCT07321652
Inclusion Criteria:
* STEP 0: This bone marrow or peripheral blood submission to Adaptive is mandatory prior to registration/randomization for real-time identification of the clone needed for MRD testing. The bone marrow sample should be from the first aspiration (i.e., first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be obtained as soon after pre-registration as possible to confirm registration eligibility
* STEP 0: Patients must be diagnosed with CLL/SLL according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria that includes all of the following:
* ≥ 5 x10\^9 /L B lymphocytes (5000/μL) in the peripheral blood (CLL) or a lymph node biopsy demonstrating SLL with the below immunophenotype (SLL)
* On morphologic review, the leukemic cells must be small mature lymphocytes
* Immunophenotype of CLL cells (performed locally) must reveal a clonal B-cell population, which coexpress the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5. Patients with bright surface immunoglobulin expression or lack of CD23 expression in \> 10% of cells must lack t(11;14) translocation by interphase cytogenetics
* STEP 0: Patients must meet criteria for treatment as defined by IWCLL 2018 guidelines which includes at least one of the following criteria:
* Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia), typically hemoglobin (Hb) \< 10 g/dL, platelet count \< 100,000/mm\^3
* Massive (\> 6 cm below the costal margin), progressive or symptomatic splenomegaly
* Massive nodes (ie, \> 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
* Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
* Constitutional symptoms, which include any of the following:
* Unintentional weight loss of ≥ 10% within the previous 6 months
* Significant fatigue (ie. Eastern Cooperative Oncology Group \[ECOG\] performance status \[PS\] ≥ 2)
* Fevers \>100.5 °F or 38.0°C for 2 weeks or more without evidence of infection
* Night sweats \> 1 month without evidence of infection
* STEP 0: Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)
* STEP 0: Treatment with rituximab and/or high-dose corticosteroids for autoimmune complications of CLL must be completed prior to enrollment. Palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
* STEP 0: Age ≥ 65 years
* STEP 0: ECOG performance status ≤ 2
* STEP 0: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* STEP 0: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* STEP 0: 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 0: Patients must not be receiving active systemic anticoagulation with warfarin. Patients must be off warfarin therapy for at least 5 half-lives washout and with normal INR prior to enrollment
* STEP 0: 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 must be class 2B or better.
Patients with acute cardiac events within 6 months prior to registration should be carefully evaluated for their suitability for enrollment
* STEP 0: No patients with a history of a severe bleeding disorder or a history of hemorrhagic stroke or intracranial hemorrhage
* STEP 0: No patients with known active progressive central nervous system (CNS) disease
* STEP 0: No known medical condition causing an inability to swallow oral formulations of agents
* STEP 1: The adaptive report confirming a measurable and trackable B cell clone
* STEP 1: Patients may not have had major surgery within 7 days of enrollment, or minor surgery within 5 days of enrollment. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. The decision about whether a surgery is major or minor can be made at the discretion of the treating physician
* STEP 1: No patients with ongoing active fungal, bacterial or viral infection requiring systemic therapy except those described in the protocol document
* STEP 1: Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily
* STEP 1: Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics
* STEP 1: Patients must not have continued requirement for therapy with a strong CYP3A4/5 inhibitor or inducer. Any such inhibitor or inducer must have been discontinued at least 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug
* STEP 1: Absolute neutrophil count (ANC) ≥ 1,000/mm3 unless due to marrow involvement
* STEP 1: Platelet count ≥ 30,000/mm3
* STEP 1: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless due to liver involvement, hemolysis or Gilbert's disease)
* STEP 1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 x upper limit of normal (ULN) unless due to disease infiltration of the liver
* STEP 1: Calculated (calc.) creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) ≥ 30 mL/min
* STEP 1: Urine protein to creatinine ratio \< 1 or urine protein ≤ 1+
* STEP 2: Detectable MRD ≥ 10 residual clonal cells per million nucleated cells in peripheral blood at the C15 restaging evaluation from ClonoSEQ
* STEP 2: Response of PR, PR-L, CR, CCR or CRi to zanubrutinib sonrotoclax therapy DRUG: Zanubrutinib, DRUG: Sonrotoclax, PROCEDURE: Computed Tomography, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Biospecimen Collection, OTHER: Survey Administration
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
Accuro XV Ultrasound Imaging System for BoneEnhance and Fracture Detection Algorithms
Delphine Le Roux, PhD - dleroux@rivannamedical.com
NCT07853768
Sites are currently on two different protocol Revisions.
Inclusion Criteria
* Age greater than or equal to 5 years.
* The patient is presenting for distal limb injury of the wrist, forearm, ankle, or lower leg.
* The patient is scheduled to receive an X-ray that includes a view of the ankle, lower leg, wrist, and/or forearm or any patient that received an X-ray accessible by the study team for the studied anatomy in the past 48 hours.
* English and/or Spanish speaking.
Exclusion Criteria
* An open fracture, grossly open wound, or severe angulation of the limb is present.
* Patients for whom the site investigator feels that study participation could prohibit or impair ongoing medical care.
* Known allergy to ultrasound couplants.
DEVICE: Accuro XV Ultrasound Imaging System
Fracture Arm, Fracture Leg, Wrist Injury, Ankle Injury
distal extremity fracture, bone fracture, musculoskeletal injury, extremity trauma, ultrasound imaging, point-of-care ultrasound, volumetric ultrasound, 3D ultrasound, bone imaging, soft tissue imaging, fracture detection, Accuro XV, Medical Device Feasibility, Image Quality, Algorithm Development
Education & Mentorship of Advanced Practice Providers to Increase Community-based Research Within the NCORP Network, COACH-APP Trial (COACH-APP)
Karen Craver - NCORP@wfusm.edu
NCT06904391
Inclusion Criteria:
* APP PRACTICE: Must have one practicing APP who can dedicate approximately 2 hours/month to participate in the intervention and study activities over a 12-month period, supported by their direct supervisor via the APP Support Statement
* APP PRACTICE: Must attest to research infrastructure that can support APP trial enrollment, as declared on the APP Practice Attestation
* APP PRACTICE: Must have submitted the APP Practice Attestation within the Study Interest Survey
* APP PRACTICE: Must have received the required APP practice ID for Oncology Patient Enrollment Network (OPEN) enrollment in the Study Selection Email prior to enrollment
* APP PRACTICE: Must enroll eligible practice site(s) in OPEN within 14 days of receiving the Study Selection Email.
* APP: Practicing nurse practitioner (NP) or physician assistant (PA) registered as an active non-physician investigators (NPIVR) within the National Cancer Institute (NCI) Registration and Credential Repository (RCR)
* APP: Treats oncology patients at practice that is actively recruiting to NCORP and/or NCTN trials
* APP: Not planning to leave their clinical position within the APP practice (defined as one or more NCORP affiliate or sub-affiliate site\[s\] where the APP participating in the study sees patients and clinical research activities occur) in the next 12 months at enrollment
* APP: Willing to participate in a 30-minute recorded phone interview, if selected
* APP: Completed and submitted the APP Attestation within the Study Interest Survey
* APP: Completed and submitted an APP Support Statement from their direct supervisor approving participation in this study, within the Study Interest Survey
* APP: Identify and obtain signed Research Care (RC) Team Acknowledgements from two members (defined below) of their research care team to assist them in this study. The RC team for this study will consist of an oncologist and clinical research professional (i.e., clinical research coordinator, clinical research associate clinical research nurse, etc.) that the APP collaborated with over the past 6 months or could collaborate with in the future to enroll patients on NCORP and/or NCTN trials
* APP: Must have received the required APP practice ID for OPEN enrollment in the Study Selection Email
* APP: Must enroll consented APPs in OPEN within 14 days of receiving the Study Selection Email
* MENTOR: Must be a practicing APP chosen by the WF-2403 COACH-APP Study MPIs
* MENTOR: Must have the following criteria:
* Clinical practice experience in a practice that enrolls to NCORP and/or NCTN trials.
* Participation in a leadership role within NCTN or NCORP (i.e., serving on a Research Base committee, working group, taskforce or as a site PI)
* Willing to complete COACH-APP mentor training.
* Willing to complete a 30-minute recorded phone interview about their experience with the COACH-APP intervention
* RESEARCH CARE TEAM INTERVIEW: Must be an identified member of the Research Care Team for an APP assigned to the COACH-APP intervention arm. The Research Care Team will be reviewed by the APP in the 12 month survey for any changes
* RESEARCH CARE TEAM INTERVIEW: Willing to participate in a recorded phone interview (approximately 30 minutes) to assess their perceptions of the COACH-APP intervention, including feasibility, acceptability, and impact
Exclusion Criteria:
* APP PRACTICE: APP practice has an APP serving as a COACH-APP intervention mentor
* APP PRACTICE: Another APP at the same APP practice is already enrolled in this study (i.e., only 1 APP is allowed per APP practice)
* APP PRACTICE: Affiliate/sub-affiliate site(s) within this APP practice are already enrolled or are intended to be enrolled in this study under another APP practice
* APP: Has already completed the SWOG APP workshop
* APP: Served as a site principal investigator (PI) for an NCORP or NCTN study at any time
* APP: Participated as a presenter for the SWOG APP workshop
* APP: Participated on the planning committee for The Advanced Practice Provider Clinical Trials Research Manual
* APP: Participated on the planning committee for the SWOG APP workshop
* APP: Past or current member of SWOG APP Task Force Committee
* APP: Past or current member of Eastern Cooperative Oncology Group- American College of Radiology Imaging Network (ECOG-ACRIN) APP Committee
* MENTOR: Must not work at NC002-Wake Forest University Health Sciences or its affiliate/subaffiliate sites OTHER: Educational Intervention, OTHER: Behavioral Intervention, OTHER: Survey Administration, OTHER: Interview
Other
Mentorship, education intervention, COACH-APP
A Study Comparing Siplizumab With Rabbit Anti-Thymocyte Globulin to Help the Body Accept a Kidney Transplant (MODERNIZE1)
ctrrecruit@vcu.edu
NCT07508787
Inclusion Criteria:
* Recipients of a renal allograft from a non-HLA identical living or deceased donor.
* Recipients of a kidney with a cold ischemia time \< 30 hours; hypothermic machine perfusion within the same timeframe is acceptable.
* Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, must agree to use highly effective methods of contraception.
Exclusion Criteria:
* Transplant recipients seronegative for EBV.
* Transplant recipients receiving a kidney from a non-heart beating donor (ie, DCD) whose organ is retrieved from an uncontrolled DCD or whose donor age \> 55 years of age.
* Multi-organ transplant recipients (eg, kidney-pancreas, organ other than kidney), dual-kidney transplant recipients, recipients with more than one prior kidney transplant, or hematopoietic stem cell transplantation recipients.
* Presence of current or historical DSA via single-antigen bead assay or local SoC. The MFI cut-off value used to determine the presence of DSA will be defined as per the institutional SoC. Results within 3 months prior to transplant are acceptable.
* Crossmatch positive (isolated positive B cell crossmatches are not an exclusion criterion).
* ABO-incompatible recipient.
* Administration of complement inhibitor therapy within 6 months prior to the transplant, or likely to require treatment with complement inhibitor therapy during the study.
* Participants receiving immunosuppressive therapies prior to transplant for pre-existing conditions must be candidates for the protocol-defined regimen.
* History of malignancy of any organ system, except for localized excised non-melanomatous skin lesions or carcinoma in situ of the cervix.
* Seropositive for human immunodeficiency virus or hepatitis B surface antigen. Participants who are seropositive for hepatitis C virus (HCV) are excluded without proof of sustained viral response after anti-HCV treatment.
* Recipient of a kidney from a donor who tests positive for human immunodeficiency virus or hepatitis B surface antigen/hepatitis B core protein.
* History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (eg, siplizumab, rATG, TAC, MPA derivatives, CS).
* Evidence of active tuberculosis (TB) infection (participants with a history of latent TB may become eligible after treatment with anti-TB therapy according to national guidelines).
* Participants with severe systemic infection(s), at the time of screening or within 2 weeks prior to randomization DRUG: Siplizumab, DRUG: Rabbit anti-thymocyte globulin
Renal Transplant Failure and Rejection
Personalized Exercise Program for Survivors of Breast Cancer, STEPS-BC Trial (STEPS-BC)
Karen Craver, MT, MHA - NCORP@wfusm.edu
NCT07474090
Inclusion Criteria:
* Stage I-III breast cancer (including inflammatory and newly diagnosed, or locally recurrent \[if prior treatment received ≥ 2 years prior\] but not metastatic breast cancer being treated with curative intent). All molecular subtypes (estrogen receptor \[ER\], progesterone receptor \[PR\], human epidermal growth factor receptor 2 \[HER2\], etc.) are acceptable
* Scheduled to receive neoadjuvant or adjuvant cytotoxic chemotherapy. Patient must be enrolled ≤ 3 weeks from start of cytotoxic chemotherapy
* Age 18 to 85 years at enrollment. The upper age cut-off is due to the increased risk of injury in the older population during the CPET, which uses stationary bicycle exercise testing, outweighing the benefit of including this age group
* Must be able to complete a stationary bicycle exercise test where you pedal against some resistance on a stationary bike with supervisors at your side per patient self-report
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting per patient self-report
* Able to hold breath for 8 seconds
* Must be able to read and understand English language
* Must have access to a device that allows teleconferencing (e.g., Zoom calls) or be willing to participate in the Tablet Lending Program
* Must be willing to download and use the Trainerize application to their personal device or be willing to participate in the Tablet Lending Program
* Must have a working email address to participate in teleconferencing (e.g., Zoom calls). Local National Cancer Institute Community Oncology Research Program (NCORP) site staff may assist in setting up a new email address, if needed
Exclusion Criteria:
* At enrollment, the following diagnosis and/or conditions may not be present (i.e., documented in the medical record or by patient self-report):
* Symptomatic claustrophobia
* Pregnancy or breast-feeding
* Ferromagnetic cerebral aneurysm clips or other intraorbital/intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted non-compatible MRI devices, such as tissue expanders
* Uncontrolled hypertension (systolic blood pressure \> 190 mm Hg or diastolic blood pressure \> 100 mm Hg)
* Inflammatory conditions such as lupus or inflammatory bowel disease, or another medical condition that might compromise safety or successful completion, as determined by the treating physician
* Significant ventricular arrhythmias (\> 20 premature ventricular contractions \[PVCs\]/min)
* Atrial fibrillation with uncontrolled ventricular response (\> 130 beats per minute \[bpm\])
* Unstable or stable angina (cardiac chest pain)
* Severe pulmonary hypertension
* Left main coronary artery disease
* Symptomatic heart failure
* Severe valvular heart disease
* Aortic aneurysm (\> 45 mm diameter) or aortic dissection
* Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise
* Hypertrophic obstructive cardiomyopathy
* Acute myocardial infarction within 28 days of enrollment
* Acute pulmonary embolus and/or deep vein thrombosis within 24 weeks prior to enrollment
* Plans to relocate within 6 months of enrollment and unable to participate in study procedures
* May not be on a simultaneous interventional supportive care (non-therapeutic) clinical trial
* May not be undergoing simultaneous treatment for a concurrent second primary cancer (patients with historical cancer will not be excluded if chemotherapy was received ≥ 2 years prior)
* May not be currently engaged in ≥ 300 minutes of moderate to vigorous intensity physical activity per week as determined by self-report on the International Physical Activity Questionnaire -Short Form (IPAQ-SF). Site should use the IPAQ-SF screener in the REDCap WF-2401 STEPS-BC screening project to assist in this determination OTHER: Exercise Intervention, OTHER: Educational Intervention, OTHER: Supportive Care, PROCEDURE: Biospecimen Collection, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Magnetic Resonance Imaging, OTHER: Questionnaire Administration, PROCEDURE: Accelerometry, OTHER: Electronic Health Record Review, OTHER: Cardiopulmonary Exercise Testing
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Breast Carcinoma, Breast Inflammatory Carcinoma, Locally Recurrent Breast Carcinoma
Surgical Thromboprophylaxis Practices in Oncology Patients Within the NCORP Network, STOP-VTE Study (STOP-VTE)
Karen Craver - NCORP@wfusm.edu
NCT07215624
Inclusion Criteria:
SURGEON ELIGIBILITY CRITERIA FOR OPEN STEP 0 ENROLLMENT:
\* Any surgeon performing gastrointestinal, genitourinary, or gynecologic cancer surgery within an NCORP site, including general surgeons, surgical specialists, urologists, and gynecologists. Surgeons do not need to be involved in research or have a Cancer Therapy Evaluation Program Identification (CTEP ID) to participate in this study
SURGICAL APP ELIGIBILITY CRITERIA FOR OPEN STEP 0 ENROLLMENT:
\* APPs providing postoperative care to patients operated by surgeons performing gastrointestinal, genitourinary, or gynecologic cancer surgery within an NCORP site, including general surgeons, surgical specialists, urologists, and gynecologists. Surgical APPs do not need to be involved in research or have a CTEP ID to participate in this study
SURGEON ELIGIBILITY CRITERIA FOR OPEN STEP 1 ENROLLMENT:
\* Must have completed the STOP-VTE Survey - Surgeon electronically (preferred) or on paper and have it transferred to Research Electronic Data Capture (REDCap) by the contact person(s)
SURGICAL APP ELIGIBILITY CRITERIA FOR OPEN STEP 1 ENROLLMENT:
\* Must have completed the STOP-VTE Survey - APP electronically (preferred) or on paper and have it transferred to REDCap by the contact person(s)
SITE ELIGIBILITY PART 1-SITE ENROLLMENT IN OPEN:
\* Have at least one eligible surgeon or surgical APP who completed the STOP-VTE Survey - Surgeon/APP
Exclusion Criteria:
* N/A OTHER: Non-Interventional Study, OTHER: Non-Interventional Study, OTHER: Non-Interventional Study
Malignant Digestive System Neoplasm, Malignant Female Reproductive System Neoplasm, Malignant Genitourinary System Neoplasm
A Study to Assess Adverse Events and Change in Disease Activity of Multiple Treatment Combinations With Intravenous Mirvetuximab Soravtansine in Adult Participants With Ovarian Cancer (FLORENZA)
ABBVIE CALL CENTER - abbvieclinicaltrials@abbvie.com
NCT07059845
Inclusion Criteria:
Substudy 1
* Participants must be willing to provide an archival tumor tissue block or slides or must undergo a procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα expression as defined by the central VENTANA FOLR1 (FOLR1-2.1) assay. Tumors must have FRα-expression in \>= 50% of viable tumor cells with \>= 2+ staining intensity.
* Participants must have an Eastern Cooperative Oncology Group performance status of 0 or 1.
* 1L participants must have a confirmed diagnosis of Federation of Gynecology and Obstetrics (FIGO) Stage III or IV high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.
2L participants must have platinum-sensitive high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Participants must have platinum-sensitive disease defined as radiographic progression greater than 183 days from the last dose of most recent platinumbased chemotherapy. Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.
* Participant has a local homologous recombination deficient (HRD) or breast cancer susceptibility gene (BRCA) test result available. Participants with BRCA wild-type will need to have a local HRD test result available.
Substudy 2
* Participants must be willing to provide an archival tumor tissue block or slides or must undergo a procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα expression as defined by the central VENTANA FOLR1 (FOLR1-2.1) assay. Tumors must have FRα-expression in \>= 50% of viable tumor cells with \>= 2+ staining intensity.
* Participants must have an Eastern Cooperative Oncology Group performance status of 0 or 1.
* Participants must have a confirmed diagnosis of high-grade serous ovarian, primary peritoneal, or fallopian tube cancer.
* Participants must have relapsed after 1 or 2 prior lines of platinum-based chemotherapy.
* Participants must have platinum-sensitive disease defined as radiographic progression greater than 183 days from the last dose of platinum-based chemotherapy.
* Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (assessed by the investigator) at baseline.
Substudy 3
* Participants must be willing to provide an archival tumor tissue block or slides or must undergo a procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα expression as defined by the central VENTANA FOLR1 (FOLR1-2.1) assay. Tumors must have FRα-expression in \>= 50% of viable tumor cells with \>= 2+ staining intensity.
* Participants must have an Eastern Cooperative Oncology Group performance status of 0 or 1.
* Participants must have a confirmed diagnosis of high-grade serous ovarian, primary peritoneal, or fallopian tube cancer.
* Participants must have relapsed after 1 or 2 prior lines of platinum-based chemotherapy.
* Participants must have platinum-sensitive disease defined as radiographic progression greater than 183 days from the last dose of platinum-based chemotherapy.
* Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (assessed by the investigator) at baseline.
Exclusion Criteria:
Substudy 1
* Participants with progressive disease (PD) while on triplet therapy or after the first day of their last triplet therapy cycle and before randomization.
* Participants who receive an intervening dose of bevacizumab after the first day of their last triplet therapy cycle and before randomization.
* Participants who received prior treatment with mirvetuximab soravtansine (MIRV), any FRα-targeting agent, or Poly(ADP-ribose) polymerase inhibitor (PARPi).
Substudy 2
* More than 2 prior lines of chemotherapy. Lines of prior anticancer therapy are counted with the following considerations:
* Neoadjuvant +/- adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens.
* Maintenance therapy (e.g., bevacizumab, PARPi) will be considered part of the preceding line of therapy (i.e., not counted independently).
* If a chemotherapeutic agent in a regimen is substituted with another during a course of treatment due to toxicity, it will be considered part of the same line of therapy
* Prior hormonal therapy will not be counted as a separate line of chemotherapy (it will be counted as part of the prior systemic therapy regimen)
* Participants who received prior treatment with mirvetuximab soravtansine or other FRα-targeting agents.
Substudy 3
* More than 2 prior lines of chemotherapy. Lines of prior anticancer therapy are counted with the following considerations:
* Neoadjuvant +/- adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens.
* Maintenance therapy (e.g., bevacizumab, PARPi) will be considered part of the preceding line of therapy (i.e., not counted independently).
* If a chemotherapeutic agent in a regimen is substituted with another during a course of treatment due to toxicity, it will be considered part of the same line of therapy
* Prior hormonal therapy will not be counted as a separate line of chemotherapy (it will be counted as part of the prior systemic therapy regimen)
* Participants who received prior treatment with mirvetuximab soravtansine or other FRα-targeting agents. DRUG: Mirvetuximab Soravtansine, DRUG: Bevacizumab, DRUG: Carboplatin
Ovarian Cancer
Ovarian Cancer, Mirvetuximab Soravtansine, Bevacizumab, Carboplatin
Testing Short-Course Radiation Versus Standard-Course Radiation for Soft Tissue Sarcomas That Need Surgery and Radiation
ctrrecruit@vcu.edu
NCT07615049
Inclusion Criteria:
* Participants must have histological evidence of a soft tissue sarcoma from core or incisional biopsy. Participants must have a primary or locally recurrent tumor. Stage II-IIIB (by American Joint Committee on Cancer \[AJCC\] 8th edition) soft tissue sarcoma is required
* Prior partial excision or partial excisional biopsy of the tumor, with imaging evidence of gross residual disease \> 1cm in longest dimension (stage II-IIIB)
* Participants must have a primary site of disease in the extremity, including the shoulder girdle and hip girdle but excluding the hands and feet
* Participants with primary sites of trunk, head, neck, or intra-abdominal, intrapelvic, or retroperitoneal region are not eligible
* Participants with extension of the primary tumor into adjacent regions (e.g. torso, hands, feet) are eligible
* Participants must have an MRI of the primary site within 90 days prior to randomization. The MRI field of view must contain the entirety of the tumor (may be accomplished with multiple MRI scans). MRI must contain axial acquired T1 weighted with fat suppression, T1 weighted sequence with gadolinium contrast with fat suppression, and T2 weighted fat suppression sequence
* Participants must have no evidence of metastatic disease by CT imaging of the chest (or positron emission tomography \[PET\] CT), within 28 days before randomization
* Given the lack of specificity of chest CT, pulmonary nodule(s) ≤ 5 mm without a histological diagnosis are not exclusionary
* Participants with pulmonary nodule(s) measuring 6-10 mm on chest CT are eligible if the nodules appear stable compared to prior chest imaging from at least 6 months ago, or if an fludeoxyglucose F-18 (18FDG)-PET scan indicates that the nodules are unlikely to be metastatic disease
* Pulmonary nodules \> 10 mm should be considered metastatic unless proven otherwise by biopsy/resection or stable appearance for at least 6 months on imaging
* Participants must not have fungating tumor. (i.e., tumor breakthrough of skin)
* Participants must not have myxoid liposarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, gastrointestinal stromal tumor, osteosarcoma, neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, desmoplastic small round cell tumor, Ewing sarcoma, or sarcoma arising from bone
* Participants must not have known brain metastases. Brain imaging studies are not required for eligibility if the participant has no neurologic signs or symptoms suggestive of brain metastasis. If brain imaging studies are performed, they must be negative for disease
* Participants must have been evaluated by a surgeon, and it must have been determined that they are a good candidate for a limb salvage resection with an expectation of negative margins, within 35 days prior to randomization. Anticipated positive margins on fixed critical structures are allowed
* Participants must not have had prior treatment for the current tumor (systemic therapy, radiation, or complete surgical resection)
* Participants must not have had prior radiation to the anatomical site
* Participants must be ≥ 18 years old at the time of randomization
* Participants must have Zubrod performance status of 0-2
* Participants must have medical history and physical exam within 28 days prior to randomization. History and physical examination must include a description of the location of the tumor, including lateralization and extremity
* 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
* 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 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 not have uncontrolled intercurrent illnesses or any other significant condition(s) that would make this protocol unreasonably hazardous
* Participants with a history 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 registration
* Participants registered by sites located in the United States only must be offered the opportunity to participate in specimen banking
* NOTE: As a part of the 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 RADIATION: 3-Dimensional Conformal Radiation Therapy, RADIATION: 3-Dimensional Conformal Radiation Therapy, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, RADIATION: Intensity-Modulated Radiation Therapy, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Surgical Procedure
Recurrent Soft Tissue Sarcoma of the Trunk and Extremities, Resectable Soft Tissue Sarcoma of the Trunk and Extremities, Soft Tissue Sarcoma of the Trunk and Extremities, Stage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8, Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
A Study to Investigate the Efficacy and Safety of Frexalimab Versus Tacrolimus in Adults Undergoing Kidney Transplantation (FREXERA)
Trial Transparency email recommended (Toll free for US & Canada) - Contact-US@sanofi.com
NCT07412470
Inclusion Criteria:
* Participants who are scheduled to receive their first kidney transplant from a living or deceased donor.
* Participants with low to moderate immunological risk.
Exclusion Criteria:
* Deceased donor kidney graft qualified as expanded criteria donor or donor after cardiac death.
* Positive T or B cell crossmatch, or positive virtual crossmatch per local practice at screening.
* Participants receiving a kidney graft from HLA-identical living-related donors, or have current or previous solid organ, cell, or multi-organ transplantation, or paired kidney transplantation.
* Participants whose primary causes of ESKD are idiopathic FSGS, C3 glomerulopathy, lupus nephritis, or thrombotic microangiopathy
* Evidence of active or latent TB, HIV, HBV or HCV infection.
* Participants who have known genetically predisposed thrombophilia, have history of thromboembolic events, or who need long-term anti-coagulation therapy.
* Participants who have severe medical co-morbidities, active infection, or severely limited life expectancy due to underlying medical conditions that are generally precluded from kidney transplant.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. DRUG: Frexalimab, DRUG: Frexalimab, DRUG: Tacrolimus, DRUG: rabbit anti-thymocyte globulin, DRUG: mycophenolate mofetil, DRUG: mycophenolate sodium, DRUG: methylprednisolone, DRUG: prednisone
Kidney Transplant Rejection
Adding Pirtobrutinib to the Usual Treatment for People With Newly Diagnosed Richter Transformation, The PIRAMID Trial
ctrrecruit@vcu.edu
NCT07220187
Inclusion Criteria:
* Participants must have been diagnosed with Richter Transformation (RT) (CLL/small lymphocytic lymphoma \[SLL\] to LBCL)
* Participants must have histologically or cytologically confirmed LBCL
* Participants must have measurable disease determined by PET/CT or hematopathology (by morphology or flow cytometry) assessment within 42 days prior to registration
* Participants must have staging PET/CT imaging performed within 42 days prior to registration
* Participants are allowed prior treatments for CLL/SLL or its complications (autoimmune hemolytic anemia \[AIHA\], immune thrombocytopenic purpura \[ITP\]), with the exception of pirtobrutinib
* Participants must not have prior treatment for Richter transformation except for corticosteroids up to equivalent dose of prednisone 700 mg total for less than 7 days for disease control. Treatment for CLL/SLL with CLL/SLL directed drugs (including BTK inhibitors with the exception of pirtobrutinib) after the Richter transformation diagnosis is allowed for the purpose of disease control. CLL targeted therapies must be stopped within 3 days before initiation of therapy on protocol. Chemotherapy or anti-CD20 monoclonal antibody therapy must be stopped within 2 weeks before initiation of therapy on protocol
* Participants must not have contraindication for receiving anthracycline. Participants must not have received more than a cumulative dose of 100mg/m\^2 in those participants who will receive R-CHOP or not more than 250 mg/m\^2 in those participants who will receive R-mini-CHOP of prior doxorubicin (or equivalent dose of another anthracycline, such as epirubicin) therapy (at any time prior to registration)
* Patients requiring strong CYP3A inducers are not eligible and can only be enrolled if
* an alternative treatment to the strong CYP3A inducer is available for them and
* the last dose of the strong CYP3A inducer is administered at least 7 days before initiation of pirtobrutinib for patients in safety run-in and arm 1
* Participant must be ≥ 18 years old at the time of registration
* Participant must have Eastern Cooperative Oncology Group (ECOG)/Zubrod Performance Status of 0-2
* Participant must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count (ANC) ≥ 0.75 x 10\^3/µL or ≥ 0.50 x 10\^3/µL in participants with suspected marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)
* Platelets ≥ 50 x 10\^3/µL or ≥ 30 x 10\^3/µL in participants with suspected marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)
* Hemoglobin ≥ 8 g/dL (≥ 80 g/L) or ≥ 6 g/dL in participants with suspected bone marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) or ≤ 3 x ULN with documented liver involvement and/or Gilbert's disease (within 28 days prior to registration)
* Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 × institutional ULN or ≤ 5 ULN with documented liver involvement (within 28 days prior to registration)
* Participants must have a calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration. For the Cockcroft-Gault formula for calculated creatinine clearance, see the tools on the CRA Workbench https://txwb.crab.org/TXWB/Tools.aspx
* Participants must have a left ventricular ejection fraction (LVEF) ≥ 45% as measured by echocardiogram or radionuclide (MUGA) ventriculography within 56 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. To be eligible for this trial, participants must be class 2B or better
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Participants' HIV-directed therapy cannot have known interactions with pirtobrutinib
* 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 registration
* 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 registration
* Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications
* Participants must not have a prior or concurrent malignancy in addition to CLL/SLL and Richter transformation 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
* Participants must not have had major surgery within 28 days prior to registration
* Participants must not have experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor.
* NOTE: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2g per deciliter; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome
* 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 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 be offered the opportunity to participate in specimen banking
* Participants must agree to have blood and lymphatic tissue specimens submitted for the integrated translational medicine study
* For randomized participants only: Participants who can complete PRO-CTCAE and FACIT GP5 questionnaires forms in English or Spanish must be offered the opportunity to participate in the patient-reported outcome PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography Test, PROCEDURE: Multigated Acquisition Scan, DRUG: Pirtobrutinib, PROCEDURE: Positron Emission Tomography, DRUG: Prednisone, BIOLOGICAL: Rituximab, BIOLOGICAL: Rituximab and Hyaluronidase Human, OTHER: Survey Administration, DRUG: Vincristine
Richter Syndrome, Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma, Transformed Small Lymphocytic Lymphoma to Diffuse Large B-Cell Lymphoma
A Study to Learn About the Medicine Ponsegromab in Adults With Cancer of the Pancreas Which Has Spread and Caused Significant Body Weight Loss and Fatigue
Pfizer CT.gov Call Center - ClinicalTrials.gov_Inquiries@pfizer.com
NCT06989437
Key inclusion Criteria:
* Signed Informed Consent Document
* Documented active diagnosis of metastatic pancreatic ductal adenocarcinoma
* Cachexia defined by Fearon criteria of weight loss
* Completed 1 x 28-day cycle of first-line systemic nab-paclitaxel and gemcitabine chemotherapy or 2 x 14-day cycles of FOLFIRINOX chemotherapy and prior to receiving Cycle 2 chemotherapy
* ECOG PS ≤1 with life expectancy of at least 4 months
Key
Exclusion Criteria:
* Current active reversible causes of decreased food intake
* Cachexia caused by other reasons
* Any prior or current clinical diagnosis of heart failure, irrespective of left ventricular ejection fraction or New York Heart Association classification
* Left ventricular ejection fraction \<50%
* Receiving tube feedings or parenteral nutrition at the time of Screening or Randomization
* History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody
* History of allergy or hypersensitivity to any of the chemotherapeutics or any of their excipients
* Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma, symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases
* Inadequate liver function
* Renal disease requiring dialysis or eGFR \<30 mL/min/1.73m2 DRUG: ponsegromab, DRUG: placebo
Cachexia, Metastatic Pancreatic Ductal Adenocarcinoma
pancreatic cancer, metastatic cancer, cancer, anorexia, cachexia, weight loss, loss of appetite, fatigue