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Integrated Therapies for Alcohol Use in Alcohol-associated Liver Disease (ITAALD) Trial (ITAALD)
Savannah Yarnelle - samussel@iu.edu
NCT07060638
Inclusion Criteria
* Age ≥18, \<70
* MELD 20-35 on day of randomization
* Definitive or probable diagnosis as defined by the NIAAA criteria
* Onset of jaundice (defined as serum total bilirubin \>3 mg/dL) within the prior 8 weeks
* Ongoing consumption of \> 40 gm (for females) and \> 60 gm (for males) alcohol daily for 6 months or more with less than 8 weeks of abstinence before onset of jaundice
* AST \> 50 IU/L,
* AST: ALT \> 1.5
* ALT and AST values \< 400 IU/L
* and/or histological evidence of AH\*
\*In patients with possible AH or AH with confounding factors such as possible ischemic hepatitis, possible DILI, uncertain history of alcohol use (e.g., patient denies excessive alcohol use), and atypical/abnormal laboratory tests (e.g., AST \< 50 IU/L or \> 400 IU/L, AST/ALT ratio \< 1.5), antinuclear antibody \> 1:160 or SMA \> 1:80, a standard of care liver biopsy may be performed during current hospital admission to confirm AH and exclude competing etiologies.
* Females of childbearing (reproductive) potential must have a negative serum or urine pregnancy test at screening.
Exclusion Criteria
* Active listing for liver transplantation before screening
* MELD score \<20 or \> 35
* Uncontrolled infection (persistent positive blood or other body fluid cultures despite 48 hours of antibiotic therapy)
* Progressive hemodynamic compromise requiring intravenous pressors
* Pneumonia as evidenced by clinical and radiological examination
* Renal failure defined by estimated GFR \<35 mL/min.
* Clinically active C. diff infection
* Evidence of other liver diseases (such as autoimmune hepatitis, primary biliary cholangiopathy, primary sclerosing cholangitis, ischemic, sepsis- or drug-induced liver disease)
* History or presence of cancer (including hepatocellular carcinoma) other than non- melanoma skin cancer
* Prior exposure to systemic corticosteroid (glucocorticoid) or immunosuppressive therapy for more than 2 days within the previous 30 days
* Current use of naltrexone or acamprosate.
* Clinically significant pancreatitis- abdominal pain, elevated lipase (\> 3 X ULN), and at least edema of pancreas with fat-stranding on CT scan
* Active gastrointestinal bleeding defined as hematemesis or melena with a decrease in hemoglobin more than 2 g/dl in 24 hours due to gastrointestinal bleeding, or with a decrease in mean arterial BP to \< 65 mmHg
* Significant concomitant medical illnesses (such as uncontrolled congestive heart failure or COPD or progressive multi-organ failure) as determined by the study investigator
* Uncontrolled mental illness as determined by the study investigator
* Uncontrolled HBV, HIV, or HCV infection with persistent viremia. However, subjects with controlled (undetectable viral load) HIV and HBV on viral suppressive therapies will be enrolled and subjects with history of HCV will be enrolled if they have evidence of SVR one year prior to enrollment
* Active illicit opiates, cocaine, ketamine, or methamphetamine use in the last 30 days.
* Uncontrolled diabetes mellitus with A1c \> 9
* Pregnancy or breastfeeding
* Known allergy or intolerance to therapeutic agents to be tested
* Unwillingness to stop alcohol use and to undergo AUD treatment
* Unwillingness to either abstain from sexual intercourse, or if sexually active, use a reliable method of birth control during the study and for at least 30 days after the last dose of the study medication. Examples of acceptable birth control methods include double barrier method such as condom and occlusive cap (diaphragm or cervical cap) with spermicidal foam/gel/film/cream/suppository; birth control pills, patches, injections, or implants; intrauterine device (IUD); vasectomy and tubal ligation.
* Participant has any condition or circumstance that adversely affects the participant, could cause noncompliance with treatment or visits, may impact the interpretation of clinical data, could cause bias, or may otherwise contraindicate the participant's participation in the study.
DRUG: IL-22, DRUG: Prednisone, DRUG: Acamprosate, DRUG: Prednisone placebo, DRUG: IL-22 (F-652) Placebo, BEHAVIORAL: Motivational Interviewing (MI), BEHAVIORAL: Motivational Enhancement Therapy (MET), BEHAVIORAL: Usual Care
Alcohol-associated Hepatitis
Severe AH, AUD
Randomized Controlled Trial of Treatment to Optimize Heart Rate Variability for Persistent Post-Concussion Symptoms
Brett Brooks - bret.brooks@vcuhealth.org
NCT07071350
Inclusion Criteria:
* age 18 or older
* History of military service
* Self-Reported hx of 1 or more mild TBI
* Most recent TBI more than 1 year ago
* Significant Persistent Post-Concussion Symptom burden (Neurobehavioral Symptom Inventory \[NSI\] total score greater than or equal to 20).
* Current Sleep Difficulties
* Fluent English
* Able to provide Informed Consent
Exclusion Criteria:
* Any TBI with severity greater than mild (i.e., Moderate or Severe TBI defined as initial injury loss of consciousness (LOC) duration \>30 minutes, posttraumatic amnesia (PTA) duration \>24 hours, or traumatic hemorrhage on head computerized tomography (CT) and determined by the study investigator based on information gathered during administration of the study's validated TBI structured interview instrument.
* Conditions or medications that can affect HRV measurement (pacemaker or an implant that stimulates your heart (e.g., cardioverter-defibrillator or ICD); heart transplant or heart surgery within the last year, including bypass or other surgery, but not including a stent)
* Hx of stroke
* Mental conditions that may impede adherence (e.g., dementia, psychotic disorder, panic disorder) OTHER: HRV Coherence Ratio, BEHAVIORAL: NSI, BEHAVIORAL: Pittsburgh Sleep Quality Index (PSQI), BEHAVIORAL: Quantitative Sleep Measures, BEHAVIORAL: Patient Global Impression of Change (PGIC), BEHAVIORAL: Cognitive Performance/NIH Toolbox Cognitive Battery, OTHER: Pain Interference/TBI-QoL Pain Interference Short-Form, BEHAVIORAL: Patient Health Questionnaire-9 (PHQ-9), BEHAVIORAL: PTSD Checklist for DSM-5 (PCL-5), OTHER: HRV Biofeedback (HRV-B), OTHER: Psychoeducational (Edu) Comparator Intervention
Autonomic Nervous System Disease, Concussive Injury, Mild Traumatic Brain Injury, Post Traumatic Stress Disorder, Persistent Post Concussion Syndrome
A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy (OrigAMI-3)
Study Contact - Participate-In-This-Study1@its.jnj.com
NCT06750094
Inclusion Criteria:
* Have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Participants must have recurrent, unresectable or metastatic disease
* Determined to have kirsten rat sarcoma viral oncogene/neuroblastoma RAS viral oncogene homolog (KRAS/NRAS), G12, G13 and v-raf murine sarcoma viral oncogene homolog B (BRAF) V600X (X represents any single amino acid change from the original amino acid) wild type status by local and/or central next-generation sequencing (NGS) testing
* Must agree to the submission of fresh or archival tumor tissue post progression from the most recent therapy, if clinically feasible
* Have measurable disease according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
* Participant must have received 1 line of systemic therapy (fluoropyrimidine-based and oxaliplatin-based) for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy. Participants can receive anti-VEGF as prior line of therapy
Exclusion Criteria:
* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: amivantamab, cetuximab or bevacizumab or any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status who has not received immunotherapy treatments
* Participant with known human epidermal growth factor receptor 2 (HER2)- positive/amplified tumor
* Has prior exposure to irinotecan, any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET) BIOLOGICAL: Amivantamab, BIOLOGICAL: Cetuximab, BIOLOGICAL: Bevacizumab, DRUG: 5-fluorouracil, DRUG: Leucovorin calcium/Levoleucovorin, DRUG: Irinotecan
Colorectal Neoplasms
Phase 2b Study to Investigate the Safety and Efficacy of TIN816 in Sepsis-associated Acute Kidney Injury (CLEAR-AKI) (CLEAR-AKI)
Novartis Pharmaceuticals - novartis.email@novartis.com
NCT05996835
Inclusion Criteria:
• Signed informed consent must be obtained in accordance with local regulations.
• ≥ 18 to ≤ 85 years of age
• Admitted to ICU or intermediate care unit/ high dependency care unit (HDU)
• Diagnosis of sepsis according to criteria defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) based on: * Suspected or confirmed infection AND * Acute increase of SOFA score of 2 or more (excluding renal component). The baseline SOFA score should be assumed to be zero unless the participant is known to have pre-existing (acute or chronic) organ dysfunction before the onset of infection
• Diagnosis of AKI Stage 1 or greater per the following criterion at randomization: An absolute increase in serum or plasma creatinine by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within 48 hours or presumed to have occurred in the previous 48 hours as compared to the reference serum creatinine. * For participants with hospital-acquired AKI, a stable serum creatinine obtained in the hospital prior to AKI diagnosis should be used as the reference serum creatinine. * For participants presenting from community, the reference serum creatinine should be estimated using the following order of preference:
• The most recent value within 3 months of the hospital admission. If not available:
• The most recent value between 3 and 12 months prior to hospital admission. If not available:
• At hospital admission Exclusion criteria
• Not expected to survive for 24 hours
• Not expected to survive for 30 days due to medical conditions other than SA-AKI
• History of CKD with a documented estimated GFR \<30 mL/min prior to admission to hospital
• eGFR \<45mL/min at admission without any other reference serum eGFR within last 12-months
• Receiving RRT or a decision has been made to initiate RRT within 24 hours after randomization
• Weight is less than 40 kg or more than 125 kg.
• Limitations to the use of mechanical ventilation, RRT or vasopressors/inotropes (N.B. limitations on Cardiopulmonary resuscitation (CPR)e.g., do-not-resuscitate orders are not an exclusion criterion unless associated with likely poor outcome in next 24 hours)
• Sepsis diagnosis according to sepsis inclusion criteria for a period longer than 72 hours prior to ICU admission
• AKI diagnosis according to AKI inclusion criteria over 48 hours after admission to ICU
• Inability to administer study drug within 24 hours of diagnosis of AKI according to AKI inclusion criteria
• Presence of AKI, in the Investigator's opinion, as suggested by clinical manifestation, e.g., prolonged oliguria or severe renal dysfunction on admission without a history of CKD, for a period longer than 24 hours prior to study drug administration
• Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization
• AKI is most likely attributable to other causes than sepsis, such as nephrotoxic drugs (Non-steroidal anti-inflammatory drugs (NSAIDs), contrast, aminoglycosides, etc.) or renal perfusion-related (acute abdominal aortic aneurysm, dissection, renal artery stenosis), urinary obstruction
• Documented (biopsy proven) or suspected history of acute or sub-acute kidney diseases such as rapidly progressive glomerular nephritis (RPGN) and acute interstitial nephritis (AIN)
• Patients who are post-nephrectomy
• Patients with permanent incapacitation
• Patients who are thrombocytopenic at screening (platelet count \<50,000 per microliter) who have active/uncontrolled bleeding or who present current or past conditions indicating high risk for bleeding in the opinion of the investigator (e.g. coagulopathies, previous history of major non-traumatic bleeding etc.)
• Immunosuppressed patients * History of immunodeficiency diseases * Receiving immunosuppressant treatment or on chronic high doses (high-dose therapy exceeding 2 weeks of treatment) of steroids equivalent to prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant patients. Patients with septic shock treated with corticosteroids (as per the Surviving Sepsis Guidelines) can be included.
• Patients with known or presumed latent or active TB based on clinical history or imaging e.g. patients on TB preventive therapy or close/household contacts of pulmonary TB patients
• Known active hepatitis B or C infection (clinical diagnosis or positive infection serology), or advanced chronic liver disease, confirmed by a Child-Pugh score of 10-15 (Class C)
• Acute pancreatitis with no established source of infection
• Active hematological malignancy (previous hematological malignancies that are not actively treated are allowable)
• Burns requiring ICU treatment
• Sepsis attributed to confirmed COVID-19
• Use of other investigational drugs within 5 half-lives of enrollment, within 30 days (e.g., small molecules) or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations
• History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes
• Any medical conditions that could significantly increase risk of participants' safety by participating in this study according to investigator's judgement
• Women with a positive pregnancy test, pregnancy or breast feeding
• Women of childbearing potential, unless they are using highly effective methods of contraception for the entire duration of the trial.
BIOLOGICAL: TIN816 70 mg lyophilisate powder, OTHER: Placebo
Acute Kidney Injury Due to Sepsis
Sepsis, acute kidney injury, anti-inflammatory, immunosuppression, intensive care unit
Comparing the Attentional Demands and Functional Outcomes in People With Transradial Amputation
Tiffany Amos - tdclory@vcu.edu
NCT07075042
Inclusion Criteria:
* 18 years of age or older
* Unilateral transradial limb loss
* At least 6 months since loss
* Previous or current use of a myoelectric device for 3 months or longer
* Use of a prosthesis at least 4 days each week
* Ability to read, write, and understand English
* Willingness to use each control strategy as primary device for 3 months each (6 months commitment total)
Exclusion Criteria:
* Any health condition that would prevent safely completing trial activities
* Discontinued use of a myoelectric prosthesis due to non-financial reasons DEVICE: Training with PRC, DEVICE: Training with DC, DEVICE: PRC Device use in community and home, DEVICE: DC Device use in community and home
Amputation
Transradial Amputation, Direct Myoelectric Control, Pattern Recognition Controller (PRC)
The Vanguard Study: Testing a New Way to Screen for Cancer
ctrrecruit@vcu.edu
NCT06995898
Inclusion Criteria:
* Ages 45-75 years old
* Agree to provide blood samples for possible MCD testing at enrollment and at 1 year following enrollment
* Agree to allow collection of information from their medical records for study-related purposes
* Understand and be able to complete informed consent and participant questionnaires in English, Spanish, or Arabic
* Note: Eligibility for Spanish and Arabic languages are at the Hub's discretion
Exclusion Criteria:
* Solid malignant tumor or blood cancer diagnosis, with or without treatment, within the last 5 years
* Note: Persons with a history of in situ cancers (e.g., ductal carcinoma in situ of the breast, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ) or nonmelanoma skin cancer are eligible
* Ongoing cancer diagnostic work-up
* Ongoing participation in another study of an investigational cancer screening test or technology
* Currently breastfeeding or pregnant, or planning to become pregnant in the next year PROCEDURE: Biospecimen Collection, DEVICE: Device Usage, OTHER: Electronic Health Record Review, PROCEDURE: Multi-Cancer Detection Test, PROCEDURE: Multi-Cancer Detection Test, OTHER: Questionnaire Administration
Bladder Carcinoma, Breast Carcinoma, Colorectal Carcinoma, Esophageal Carcinoma, Gastric Carcinoma, Liver Carcinoma, Lung Carcinoma, Malignant Solid Neoplasm, Ovarian Carcinoma, Pancreatic Carcinoma, Prostate Carcinoma
Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)
ctrrecruit@vcu.edu
NCT05638295
Inclusion Criteria:
* Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-E5 based on the presence of an actionable mutation as defined in EAY191
* Patient must be enrolled on the ComboMATCH Registration Protocol (EAY191) at the time of registration/randomization to the EAY191-E5 study
* Patient must be \>= 18 years of age
* Patient must have a KRAS G12C alteration as determined by the ComboMATCH screening assessment
* Patient must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191-E5)
* NOTE: The current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website: www.ctsu.org (final URL pending)
* NOTE: Novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH registration protocol
* Patient must have cytologically/histologically confirmed advanced/metastatic solid tumor
* Patient must have progressed on at least one line of standard of care therapy in the advanced/metastatic setting
* NOTE: Patients who have progressed on a prior human epidermal growth factor receptor (EGFR) inhibitor will meet this criterion
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 (or Karnofsky performance status \>= 60%)
* Patient must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) documented by imaging obtained within 28 days prior to registration/randomization
* Patient must not have any serious active infection within 4 weeks prior to EAY191-E5 registration/randomization (e.g., requiring hospitalization and/or intravenous \[IV\] antibiotics) or currently receiving oral or IV antibiotics for the treatment of infection. Patients receiving prophylactic antibiotics are eligible
* Patient must have the ability to retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption
* Patient must not have any history of or current evidence of non-infectious interstitial lung disease (ILD)/pneumonitis
* Patient must not have a history of allergic reactions attributed to either of the study agents or to agents of similar chemical or biologic composition
* Patient must have completed full treatment cycle 21 days prior to EAY191-E5 registration/randomization if they have received prior chemotherapy, biological cancer therapy, radiation therapy or an investigational agent/device. Patients must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse events due to prior cancer therapy (with the exception of alopecia)
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration/randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 6 months after the last dose of protocol treatment. Patients must not breastfeed while receiving protocol treatment and for one week (7 days) after the last dose of AMG 510 (sotorasib) and 2 months after the last dose of panitumumab
* Patients must not have neuropathy ≥ grade 2 within 14 days prior to registration/randomization
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* Human immunodeficiency virus (HIV)-infected patients no effective anti-retroviral therapy with undetectable viral load within 6 months 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 history, 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 trail, patients should be class 2B or better
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 28 days prior to protocol registration/randomization)
* Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (\[SGPT\]) \< 3 x institutional upper limit of normal (obtained ≤ 28 days prior to protocol registration/randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \> 50 mL/min/1.73 m\^2 for patients with creatinine levels \> 1.5 mg/dL as per Cockcroft-Gault (obtained ≤ 28 days prior to protocol registration/randomization)
* COHORT I: Patient must not have colorectal cancer or non-small cell lung cancer
* COHORT I: Patient must not have been previously treated with a KRAS G12C inhibitor
* COHORT II: Patient must have progressed after treatment at the recommended phase II dose (RP2D) of any KRAS G12C inhibitor
* NOTE: Patients on cohort 1 who experience progression on Regimen 2 (AMG 510 \[sotorasib\] alone) may be eligible to enroll on cohort 2 and receive combination treatment with panitumumab and AMG 510 (sotorasib). Patients must meet performance status requirements and laboratory values as above and must be begin treatment within 7 days of enrollment. Migration to cohort 2 must take place within 6 months of progression, with no intervening anti-cancer therapy given.
* NOTE: Cohort migration following disease progression is dependent on a slot being available. MATCHBox makes the new treatment assignment following initiation of a step 2 registration for this treatment trial
* COHORT II: Patient must not have been previously treated with a KRAS G12C inhibitor in combination with an EGFR inhibitor PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Panitumumab, DRUG: Sotorasib
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
Naxitamab Added to Induction for Newly Diagnosed High-Risk Neuroblastoma
BCC Enroll - BCCEnroll@pennstatehealth.psu.edu
NCT05489887
Inclusion Criteria:
• Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:
• Subjects with newly diagnosed neuroblastoma with INRGSS Stage M disease with either of the following features:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
• 365 days to ≥ 547 days of age without MYCN amplification, but unfavorable biologic features such as unfavorable histology (INPC) or diploid tumor (DNA index=1) or the presence of any segmental chromosome aberration (SCA) (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q); OR
• Age \> 547 days of age regardless of biologic features Subjects with newly diagnosed neuroblastoma with INRGSS Stage MS disease with either of the following:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals); OR
• 365 days to ≥ 547 days (18 months) of age without MYCN amplification, but unfavorable biologic features such as unfavorable histology (INPC) or diploid tumor (DNA index=1) or SCA as above Subjects with newly diagnosed neuroblastoma INRGSS Stage L2 disease with either of the following:
• MYCN amplification (\> 4-fold increase in MYCN signals as compared to reference signals); OR
• 18 months to \<5 years of age without MYCN amplification, but with unfavorable histology (INPC); OR
• ≥5 years of age without MYCN amplification, but with undifferentiated or poorly differentiated INPC Subjects with newly diagnosed neuroblastoma INRGSS Stage L1 disease that is incompletely resected with MYCN amplification. Subjects \> 547 days of age initially diagnosed with INRGSS Stage L1, L2 or MS disease who progressed to Stage M without prior chemotherapy may enroll within 4 weeks of progression to Stage M. Subjects ≥ 365 days of age initially diagnosed with MYCN amplified INRGSS Stage L1 disease who progress to Stage M without systemic therapy may enroll within 4 weeks of progression to Stage M.
• Subjects must be age ≤ 21 years at initial diagnosis.
• Subjects must be \>12 months of age at enrollment.
• Adequate cardiac function defined as:
• Shortening fraction of ≥ 27% by echocardiogram, or
• Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.
• Adequate liver function must be demonstrated, defined as:
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
• ALT (SGPT) \< 5 x upper limit of normal (ULN) for age
• Subjects must have adequate renal function defined as an estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr
• A negative serum pregnancy test is required for female participants of childbearing potential (≥13 years of age or after onset of menses)
• Both male and female post-pubertal study subjects must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of \<1% per year when used consistently and correctly) from the time of informed consent until 6 months after study treatment discontinuation. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence.
• Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria:
• Subjects who are less than 1 year of age
• Subjects who are 12-18 months of age with INRGSS Stage M and all stage L2 subjects with favorable biologic features (i.e., nonamplified MYCN, favorable pathology, and DNA index \> 1) are not eligible.
• Subjects who have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy.
• Treatment with immunosuppressive treatment (topical, inhaled and short-term emergency steroids excluded) within 4 weeks prior to enrollment
• Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry \< 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
• Subjects receiving any investigational drug concurrently.
• Subjects with any other medical condition, including but not limited to malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study
• Subjects with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of investigational medicinal products (IMPs) or to significantly increase the severity of the toxicities experienced from trial treatment.
DRUG: Naxitamab
Neuroblastoma
naxitimab, induction
Pulmonary Hypertension Association Registry (PHAR)
Elizabeth Joseloff, PhD - PHAR@PHAssociation.org
NCT04071327
Inclusion Criteria:
* All age groups
* Written informed consent
* Pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), or pediatric PH due to developmental lung disease
* Within 6 months of first outpatient visit at a PH Care Center
Exclusion Criteria:
* Diagnosis of WSPH Group 2 pulmonary hypertension
* Diagnosis of WSPH Group 3 pulmonary hypertension, except PH due to developmental lung disease
* Diagnosis of WSPH Group 5 pulmonary hypertension Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension, Pulmonary Hypertension
A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer
Jayson Garmizo - jayson.garmizo@immunitybio.com
NCT02138734
Inclusion Criteria
• Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology).
• Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only).
• Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 6 calendar weeks (inclusive of 48 days) of treatment start (residual CIS is acceptable; patients with T1 disease must undergo repeat resection if muscularis propria is not present in each biopsy sample). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
• Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy.
• Currently eligible for intravesical BCG therapy.
• Age ≥ 18 years.
• Performance status: ECOG performance status of 0, 1, or 2.
• BCG-naive disease as defined as either of the following:
• Have not received prior intravesical BCG; or
• Previously received BCG, but stopped receiving more than 3 years before date of randomization.
• Laboratory tests performed within 21 days of treatment start:
• Absolute lymphocyte count ≥ Institutional lower limit of normal
• Absolute neutrophil count (AGC/ANC) ≥ 1,000/μL
• Platelets ≥ 100,000/µL \[Patients may be transfused to meet this requirement\]
• Hemoglobin ≥ 8 g/dL \[Patients may be transfused to meet this requirement\]
• Calculated glomerular filtration rate (GFR\*) \>40 mL/min or Serum creatinine ≤ 1.5 x ULN
• Total bilirubin ≤ 2.0 X ULN
• AST, ALT, ALP ≤ 3.0 X ULN
• Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT \> 50% FEV1 if clinically indicated by the investigator.
• Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
• Female participants of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study.
• Provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations. * using the following Cockcroft-Gault equation to calculate the eGFR for this study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female Exclusion Criteria
• Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine following the most recent screening TURBT/biopsy are excluded.
• Concurrent use of other investigational agents (not including FDA-authorized drugs for the prevention and treatment of COVID-19).
• History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer or any other cancer within the past 5 years, except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage 1 or 2 cancer from which the patient is currently in complete remission, or stable prostate cancer (under active surveillance or hormone control).
• Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class III or IV or other clinical signs of severe cardiac dysfunction.
• Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry.
• History or evidence of uncontrollable CNS disease.
• Known HIV-positive.
• Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
• Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions.
• Ongoing chronic systemic steroid therapy required (\>10 mg oral prednisone daily or equivalent).
• Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Other illness that in the opinion of the investigator would exclude the patient from participating in this study.
• Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology).
• Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only).
• Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 6 calendar weeks (inclusive of 48 days) of treatment start (residual CIS is acceptable; patients with T1 disease must undergo repeat resection if muscularis propria is not present in each biopsy sample). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
• Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy.
• Currently eligible for intravesical BCG therapy.
• Age ≥ 18 years.
• Performance status: ECOG performance status of 0, 1, or 2.
• BCG-naive disease as defined as either of the following:
• Have not received prior intravesical BCG; or
• Previously received BCG, but stopped receiving more than 3 years before date of randomization.
• Laboratory tests performed within 21 days of treatment start:
• Absolute lymphocyte count ≥ Institutional lower limit of normal
• Absolute neutrophil count (AGC/ANC) ≥ 1,000/μL
• Platelets ≥ 100,000/µL \[Patients may be transfused to meet this requirement\]
• Hemoglobin ≥ 8 g/dL \[Patients may be transfused to meet this requirement\]
• Calculated glomerular filtration rate (GFR\*) \>40 mL/min or Serum creatinine ≤ 1.5 x ULN
• Total bilirubin ≤ 2.0 X ULN
• AST, ALT, ALP ≤ 3.0 X ULN
• Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT \> 50% FEV1 if clinically indicated by the investigator.
• Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
• Female participants of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study.
• Provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations. * using the following Cockcroft-Gault equation to calculate the eGFR for this study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female Exclusion Criteria
• Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine following the most recent screening TURBT/biopsy are excluded.
• Concurrent use of other investigational agents (not including FDA-authorized drugs for the prevention and treatment of COVID-19).
• History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer or any other cancer within the past 5 years, except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage 1 or 2 cancer from which the patient is currently in complete remission, or stable prostate cancer (under active surveillance or hormone control).
• Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class III or IV or other clinical signs of severe cardiac dysfunction.
• Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry.
• History or evidence of uncontrollable CNS disease.
• Known HIV-positive.
• Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
• Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions.
• Ongoing chronic systemic steroid therapy required (\>10 mg oral prednisone daily or equivalent).
• Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Other illness that in the opinion of the investigator would exclude the patient from participating in this study.
BIOLOGICAL: BCG+N-803( 50mg BCG/ Instillation+ N-803( 400 μg/instillation). ), BIOLOGICAL: BCG( 50mg/Instillation)
Non-muscle Invasive Bladder Cancer
antitumor, BCG, bladder cancer, cancer, immunotherapy, instillation, interleukin-15, intravesical, naive, non-muscle invasive, transitional cell carcinoma, ALT-803, N-803
Peer Support for Adolescents and Emerging Adults With Sickle Cell Pain (PRESENCE)
Steffi Siebert, MPH - presencestudy@pitt.edu
NCT06374238
Inclusion Criteria:
• Aged 16 to 30 years of age at time of enrollment
• Sickle Cell Disease diagnosis of any genotype based on referral or documentation
• Reports chronic pain (≥4 days/week for past 3 months or more) OR A) Being prescribed pain medication to be taken (≥4 days/week for past 3 months or more) OR B) Taking pain medication (≥4 days/week for past 3 months or more) OR C) Receiving non-pharmaceutical pain treatment (≥4 days/week for past 3 months or more)
• Access to an iOS or Android mobile device with internet access
Exclusion Criteria:
• Unable to speak or read English
• Prior hematopoietic stem cell transplant for sickle cell disease
BEHAVIORAL: CBT+ Health coach, BEHAVIORAL: CBT w/o Health Coach ( self-guided), BEHAVIORAL: Usual Care
Pain, Sickle Cell Disease
Sickle Cell Disease, Pain management, Cognitive Behavioral Therapy, Wellness
A Study to Find Out How EMPAgliflozin is Tolerated and if it Helps Children and Adolescents With Chronic KIDNEY Disease (EMPA-KIDNEY® Kids)
Boehringer Ingelheim - clintriage.rdg@boehringer-ingelheim.com
NCT07107945
Inclusion Criteria:
* Signed and dated written informed consent provided by the patient's parent(s) (or legal guardian) and patient's assent in accordance with international council for harmonisation good clinical practice (ICH-GCP) and local legislation prior to admission to the trial (informed assent will be sought according to the patient's age, level of maturity, competence, and capacity).
* Age 2 to 17 years at screening Visit 1.
* Chronic kidney disease (CKD) of any underlying aetiology defined by (as measured by central laboratory at screening Visit 1): estimated glomerular filtration rate (eGFR) (U25Crea) ≥20 to \<90 mL/min/1.73 m2 with a urine-albumine-creatinine (UACR) ≥300 mg/g
* Participants must be on a stable dose of maximally tolerated standard of care (SoC) therapy for 30 days before screening visit 1 with no plans to change the dose throughout the duration of the placebo-controlled duration of the trial. SoC is anticipated to include a single Renin-angiotensin-aldosterone system (RAAS) inhibitor, such as angiotensin receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEi) as appropriate and tolerated. Additional use of a mineralocorticoid receptor antagonist (MRA, including finerenone if available) is permitted if needed and the dose is stable for 30 days before screening Visit 1 and no planned dose changes for the placebo-controlled portion of the trial.
* Participants receiving daily immunosuppressive therapy for an underlying immunological cause of CKD must be on a stable dose for the duration specified for each drug prior to screening and must remain on a stable regimen throughout the placebo-controlled portion of the trial.
* Further inclusion criteria apply.
Exclusion Criteria:
* Confirmed type 1 or type 2 diabetes mellitus.
* History of ketoacidosis within 8 weeks prior to Visit 1 and up to randomisation.
* Chronic dialysis or functioning kidney transplant or scheduled for transplantation throughout the duration of the trial.
* Diagnosis of uncontrolled metabolic bone disease (at the Investigator's discretion).
* Body mass index (BMI) ≤10th percentile for children ≥4 years of age and ≤25th percentile for children \<4 years of age according to Centers for Disease Control and Prevention (CDC) growth chart at screening Visit 1.
* Gastrointestinal disorders that might interfere with trial drug absorption according to investigator assessment.
* Presence of acute or active urinary tract infection (UTI) with signs or symptoms of an active UTI or therapeutic treatment for an active UTI within 14 days before screening Visit 1.
* Severe, uncontrolled hypertension (based on investigator's judgement).
* Further exclusion criteria apply. DRUG: Empagliflozin, DRUG: Placebo
Chronic Kidney Disease
INBRX-106 in Combination With Pembrolizumab in First-line PD-L1 CPS≥20 HNSCC (HexAgon-HN)
Study Director - Inhibrx - clinicaltrials@inhibrx.com
NCT06295731
Inclusion Criteria:
* Has histologically or cytologically confirmed diagnosis of metastatic, recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies.
* Has tumor PD-L1 expression of CPS ≥20. Tumor tissue must be provided for PD-L1 biomarker analysis.
* Has human papilloma virus (HPV) testing results for oropharyngeal cancer by p16 immunohistochemistry (IHC) testing.
* Has measurable disease per RECIST 1.1 guidelines.
* Has the primary tumor location of the oral cavity, oropharynx, hypopharynx, or larynx.
* Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Female patients of childbearing potential must have a negative highly sensitive pregnancy test within 72 hours prior to randomization and must not be breastfeeding.
* Male and female patients of childbearing potential must be willing to completely abstain from heterosexual sex or agree to use a highly effective method of contraception.
Exclusion Criteria:
* Has primary tumor site (any histology) of nasopharynx or salivary glands or occult primary site.
* Has received prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for locally advanced unresectable or metastatic HNSCC.
* Prior systemic therapy completed \>6 months prior to signing informed consent is allowed if given as part of multimodal treatment for locoregionally advanced disease with curative intent, and no PD/recurrence occurred within 6 months of its completion. Prior systemic immunotherapy in the locoregionally advanced disease with curative intent, including but not limited to anti-PD-(L)1 agents, is allowed if PD/recurrence occurred ≥12 months after its completion.
* Has clinically active central nervous system metastases and/or carcinomatous meningitis.
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
* Rapidly progressing disease or with features that may confer a high risk of tumor-associated hemorrhage or uncontrolled tumor pain.
* Current or history of immune-related disease that required systemic treatment in past 2 years, except for replacement therapy. DRUG: INBRX-106, DRUG: Pembrolizumab
Head and Neck Squamous Cell Carcinoma (HNSCC)
OX40 receptor agonist, PD-L1 positive, Pembrolizumab, Immunotherapy, Chemotherapy-free, HNSCC, Head and Neck Cancer, Keytruda, Oropharyngeal cancer, Hypopharyngeal cancer, Laryngeal cancer, Oral cancer, INBRX-106
Lanreotide Versus Placebo Before Surgery to Prevent a Surgical Complication Called a Pancreatic Fistula
Andrea Garcia - agarcia@swog.org
NCT06807437
Inclusion Criteria:
* Participants must have histologically or radiographically confirmed diagnosis of pancreatic cancer or a pancreatic lesion with malignant potential
* Participants must have an elective distal pancreatectomy planned to occur within 60 days after registration/randomization date
* Participants must not have a known history of a prior diagnosis of malabsorption syndrome
* Participants must not have been treated with any somatostatin analogue within 180 days prior to registration/randomization
* Participants must not have been treated with radiation therapy for their pancreas malignancy at any time prior to registration/randomization
* Participants must not have been treated with peptide receptor radionuclide therapy (PRRT) at any time prior to registration/randomization
* Participants must be ≥ 18 years old
* Participants must have a complete documented medical history and physical exam within 28 days prior to registration/randomization
* Participants must have a creatinine ≤ the institutional upper limit of normal (IULN) OR a measured OR calculated creatinine clearance ≥ 50 mL/min using the following Cockcroft -Gault formula within 60 days prior to registration/randomization
* Participants must complete a pre-registration screening to identify any of the medications below, allowing the study team and treating physician to develop a monitoring plan as needed. Participants taking medications with known interactions with lanreotide may remain eligible if appropriate monitoring and management are in place. These medications include:
* Diabetes medications (insulin or oral hypoglycemics): Blood sugar will be monitored, and medication dose adjustments made as needed
* Cyclosporine: Dosage adjustments may be required to maintain therapeutic levels
* Bromocriptine: Dose adjustments may be considered to account for absorption changes
* Heart medications (e.g., beta blockers): Heart rate will be monitored, and medication doses adjusted if necessary
* CYP3A4-metabolized medications: Dose adjustments may be considered to avoid increased exposure
* In the opinion of the treating surgeon, based on preoperative data, the participant must not require a modified Appleby-type procedure (distal pancreatectomy with celiac axis resection) or multivisceral resection (e.g., stomach, colon, etc.) at the time of distal pancreatectomy
* NOTE: planned removal of the gallbladder or spleen at the time of distal pancreatectomy is not considered multivisceral resection and is permissible
* In the opinion of the treating surgeon, based on preoperative data, the participant must not require a tumor enucleation
* Participants must not have moderate to severe hepatic impairment as defined by liver enzyme elevation more than 5 times the institutional upper limit of normal (either aspartate aminotransferase \[AST\] \> 190 U/L or alanine aminotransferase \[ALT\] \> 320 U/L) within 60 days prior to registration/randomization. Transient elevation at the time of screening that resolves prior to study enrollment is acceptable
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped)
* Individuals who are of reproductive potential must have agreed to use an effective contraceptive method during the whole period of the study and for three months after the study drug administration, 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 who can complete EORTC QLQ-C30, EORTC QLQ-PAN26, and EQ-5D-5L forms in English or Spanish, must be offered the opportunity to participate in the quality-of-life study
* 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 PROCEDURE: Biospecimen Collection, PROCEDURE: Distal Pancreatectomy, DRUG: Lanreotide, OTHER: Questionnaire Administration, OTHER: Saline
Pancreatic Carcinoma, Pancreatic Neoplasm
A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer (OrigAMI-2)
Study Contact - Participate-In-This-Study1@its.jnj.com
NCT06662786
Inclusion Criteria:
* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Determined to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor by local and/or central testing (if available)
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
Exclusion Criteria:
* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
* Has prior exposure to any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET) BIOLOGICAL: Amivantamab, BIOLOGICAL: Cetuximab, DRUG: 5-fluorouracil, DRUG: Leucovorin calcium/Levoleucovorin, DRUG: Oxaliplatin, DRUG: Irinotecan Hydrochloride
Colorectal Neoplasms
Olutasidenib Single Plus Combo Therapy in IDH1mut AML After Induction and Consolidation
Massey IIT Research Operations - masseyepd@vcu.edu
NCT07130695
Inclusion Criteria:
* Histologically or cytologically confirmed non-acute promyelocytic isocitrate dehydrogenase (1 IDH1) mutant acute myeloid leukemia (AML). IDH1 mutation may be identified by NGS or PCR based methods and identified at time of diagnosis or any other time point prior to enrollment.
* Completed induction and/or consolidation intended as per treating physician to reach complete response (CR),complete response with partial hematologic recovery (CRh), or complete response with incomplete hematologic recovery (CRi), or morphologic leukemia free state (MLFS) at time of study enrollment Patients must be within 90 days of their last cycle of upfront therapy.
* Age ≥18 years
* Calculated creatinine clearance (by Cockroft-Gault) ≥30 mL/min
* Total bilirubin ≤2 × upper limit of normal (ULN) Note: patients with Gilbert's syndrome may be included if total bilirubin is ≤3 × ULN and direct bilirubin is ≤2 × ULN
* Serum aspartate aminotransferase/ alanine aminotransferase (AST/ALT) ≤3 × ULN
* Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2 or KPS \>50%
* Able to take oral medications
* Women of childbearing potential must consent to effective contraception during study treatment and at least 6 months following the last dose. Effective methods of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double- barrier methods. (ie, combination of male condom with either cap, diaphragm or sponge with spermicide)
* Male participants who are sexually active with a woman of childbearing potential and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug.
Exclusion Criteria:
* History of hypersensitivity or allergic reaction to olutasidenib or its components
* Corrected Q-T interval (QTc) (Fredericia calculation) \> 450 ms (after corrective action is taken)
* History of Torsades de Pointes
* Any gastrointestinal condition thought by the treating investigator to impair oral absorption of medication
* Stem cell transplant eligible and planned within 60 days of study start date in the opinion of the treating investigator
* Uncontrolled intercurrent illness or infection (those with controlled human immunodeficiency virus (HIV), hepatitis, or other chronic infections are eligible)
* Female participants who are pregnant or intend to donate eggs during the study or for 6 months after receiving their last dose of study drug
* Nursing women, women of childbearing potential with positive pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. (Appropriate method(s) of contraception include oral or injectable hormonal birth control, IUD, and double-barrier methods)
* Male participants who intend to donate sperm during the course of this study or for 3 months after last dose
* Participants receiving, or are expected to require during the study, any concomitant medications that may interfere with efficacy, metabolism, or safety of the investigational agent, including drugs known to cause QT prolongation. for which drug interactions with olutasidenib would be prohibitory
* Concurrent chemotherapy for non-AML malignancy that is expected to interfere with the efficacy, metabolism, or safety of the agent under investigation
* Received non-intensive upfront therapy including hypomethylating agents (HMA) /Venetoclax based
* Currently receiving other targeted therapies or AML directed therapies, including but not limited to other IDH1 or IDH2 inhibitors, FMS-like tyrosine kinase 3 (FLT3) inhibitors, B-cell lymphoma 2 (BCL-2) inhibitors, menin inhibitors
* Other investigational agents in another clinical trial within 4 weeks prior to enrollment
* Systemic corticosteroids above physiologic replacement doses (10mg/day prednisone or equivalent), unless used to tread IDH differentiation syndrome or as part of a pre-specified protocol exception
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the participant's risk or limit the participant's adherence with study requirements DRUG: Olutasidenib Investigational Agent Administration
Acute Myeloid Leukemia
Acute Myeloid Leukemia
A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)
ctrrecruit@vcu.edu
NCT06401330
Inclusion Criteria:
* Patients must be enrolled on APEC14B1 and consent to Part A - Eligibility Screening prior to enrollment on AREN2231.
* Patients must be \< 30 years old at enrollment.
* Patients with newly diagnosed Stage I-IV Favorable Histology Wilms Tumor confirmed by central review and with a qualifying Initial Stratum Assignment on APEC14B1.
* Patients must receive a qualifying Initial Stratum Assignment on APEC14B1-REN by Day 14 post-diagnostic procedure (nephrectomy or biopsy), where that procedure is Day 0.
* Patients must enroll on AREN2231 by Day 14.
* Exceptions: If patient reaches Day 14 (post initial diagnostic nephrectomy or biopsy) without receiving an Initial Stratum Assignment on APEC14B1-REN, patient will not be eligible for enrollment on AREN2231 unless all required materials (reports and Case Report Forms and specimens) for an Initial Stratum Assignment arrived by Day 7, but an Initial Stratum Assignment was not completed by Day 14. In these circumstances, after obtaining appropriate protocol consent, the patient may proceed with treatment according to local institutional staging and enroll within 5 calendar days of notification of the central Initial Stratum Assignment being issued, only if the AREN2231 Initial Stratum Assignment is in agreement with any treatment already initiated. If the Initial Stratum Assignment is not in agreement with the local institution's assessment then the patient will be ineligible for AREN2231.
* All sites must have sent or plan to send diagnostic tumor sample for molecular testing through a Clinical Laboratory Improvement Act (CLIA)-certified (or equivalent if outside of the United States \[US\]) laboratory that can detect Loss of Heterozygosity (LOH) of chromosome 1p AND 16q, and gain of chromosome 1q. Patients potentially eligible for mVLR must also have LOH of chromosome 11p15 included.
* Note: Patients are eligible for enrollment prior to obtaining these molecular testing results, and it is strongly recommended that patients are enrolled before these results are available. However, molecular results must be returned and uploaded to APEC14B1-REN for integration into risk stratification by the required timepoints (specific timelines vary by treatment arm). Patients who do not have molecular results available by the arm-specific timepoints may be taken off protocol therapy.
* Patients who have an upfront nephrectomy must have at least one lymph node sampled and confirmed as a lymph node by central pathology review to be eligible.
* Note: Lymph node sampling will also be required at delayed nephrectomy. Patients who do not have a lymph node sampled and confirmed as a lymph node by central pathology review at delayed nephrectomy will be taken off protocol therapy.
* Karnofsky performance status must be ≥ 50 for patients \> 16 years of age and the Lansky performance status must be ≥ 50 for patients ≤ 16 years of age.
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR direct bilirubin ≤ 3X ULN for subjects with total bilirubin levels \> 1.5 ULN (within 7 days prior to enrollment).
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Aspartate aminotransferase (AST/serum glutamate oxaloacetic transaminase \[SGOT\]) OR alanine transaminase (ALT/serum glutamic pyruvate transaminase \[SGPT\]) ≤ 3X ULN OR ≤ 5 X ULN for patients with liver metastases (within 7 days prior to enrollment).
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% (within 7 days prior to enrollment)
* Note: This criteria only applies to patients centrally classified as Stage IV. Stage II and III patients subsequently assigned to a doxorubicin arm will be off protocol therapy if they do not meet this criteria at time of cardiac function assessment.
* Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
* Patient with a diagnosis of Stage V Bilateral Wilms Tumor.
* Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible.
* Patients with any uncontrolled, intercurrent illness including but not limited to symptomatic congestive heart failure.
* Patients with Stage I FHWT with a known or suspected Wilms Tumor predisposition syndrome or condition (contralateral nephrogenic rests and/or unilateral multicentric tumors) are excluded from treatment on the mVLR (Nephrectomy Only) arm.
* Notes:
* In the context of the renal tumor protocols, multicentric tumors and multifocal tumors are equivalent terms, and refer to the occurrence of two or more tumors arising within one kidney.
* Exclusion from the Nephrectomy Only arm applies to two groups of patients:
* Patients \< 4 years with Stage I FHWT other than epithelial subtype AND
* Stage I patients of any age with Epithelial WT
* For the purpose of exclusion from the Nephrectomy Only Arm, known or suspected WT predisposition syndromes or conditions are defined as follows:
* WT Predisposition Syndromes: Beckwith Wiedemann Spectrum, Denys Drash, Trisomy 18, Idiopathic Hemihypertrophy/Isolated Lateralized Overgrowth, WAGR, Simpson-Golabi-Behmel, Bohring-Opitz, or other conditions considered by treating physician to predispose to WT.
* WT Predisposing Conditions:
* A unilateral WT and (radiologic or pathologic) determination of contralateral nephrogenic rest(s) AND/OR
* Unilateral multicentric WT
* Patients treated with partial nephrectomy at initial diagnosis are excluded from mVLR (Nephrectomy Only) arm.
* Patients with lung metastases as the only metastatic site who already had complete resection of all radiologically evident lung nodules, and have at least one nodule confirmed pathologically as tumor.
* Please note: Those with lung metastases as the only metastatic site who have complete resection of all radiologically evident lung nodules after enrollment but prior to the lung imaging following Cycle 2 of DD-4A will be inevaluable for lung assessment and subsequent stratum assignment and will, therefore, come off protocol therapy.
* Patients with known Charcot-Marie-Tooth syndrome.
* Patients who have had prior tumor-directed chemotherapy or radiotherapy for the current diagnosis except for therapy delivered for an emergent issue, as medically indicated.
* Patients who will potentially require doxorubicin on this study and have previously received doxorubicin for another diagnosis.
* Patients receiving concurrent chemotherapy for a different diagnosis.
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation. PROCEDURE: Bone Scan, DRUG: Carboplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Doxorubicin, DRUG: Etoposide, DRUG: Irinotecan, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Nephrectomy, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine, PROCEDURE: X-Ray Imaging
Stage I Mixed Cell Type Kidney Wilms Tumor, Stage II Mixed Cell Type Kidney Wilms Tumor, Stage III Mixed Cell Type Kidney Wilms Tumor, Stage IV Mixed Cell Type Kidney Wilms Tumor
Testing the Use of Ado-Trastuzumab Emtansine Compared to the Usual Treatment (Chemotherapy With Docetaxel Plus Trastuzumab) or Trastuzumab Deruxtecan for Recurrent, Metastatic, or Unresectable HER2-Expressing Salivary Gland Cancers
ctrrecruit@vcu.edu
NCT05408845
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of HER2-positive OR HER2-low expressing recurrent/metastatic salivary gland cancer (SGC)
* HER2-positive cohort:
* Note: The majority of HER2-positive SGCs are salivary duct carcinoma (SDCs), but to a lesser extent, other SGC subtypes can be HER2-positive (e.g., adenocarcinomas, mucoepidermoid carcinomas, etc.) and are eligible to be included on the study. Additionally, pathologists may sign out SDCs under other descriptors (e.g., ex-pleomorphic adenoma, adenocarcinoma), and these would be eligible if they are HER2-positive.
* Note: HER2 evaluation based on local site immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH), or local/commercial next-generation sequencing (NGS) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-positive":
* Immunohistochemistry (IHC) (3+) per the College of American Pathologists (CAP) breast cancer guidelines
* Gene amplification by FISH (HER2/CEP17 ratio \>= 2.0)
* Gene amplification by NGS (fold change \>= 2)
* HER2-low expressing cohort:
* Note: Local HER2 evaluation by immunohistochemistry (IHC) or fluorescent in-situ hybridization (FISH) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-low":
* IHC 1+ per the College of American Pathologists (CAP) breast cancer guidelines
* IHC 2+ without evidence of amplification by FISH
* Patients with unresectable disease who are not candidates for curative surgery or radiation OR recurrent OR metastatic disease that is evident on radiologic imaging
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* HER2-positive cohort: Measurable or non-measurable disease by the RECIST v1.1 criteria. HER2-low expressing cohort: Measurable disease by the RECIST v1.1 criteria
* History/physical examination within 30 days prior to registration
* The following imaging within 60 days prior to registration:
* CT or MRI of the neck (diagnostic quality with contrast, unless contraindicated) AND
* CT scan of the chest (diagnostic quality with contrast, unless contraindicated) AND
* If clinically indicated, CT or MRI of the abdomen and pelvis (diagnostic quality with contrast, unless contraindicated)
* Age \>= 18
* Left ventricular ejection fraction (LVEF) \>= 50% assessed by echocardiogram or multigated acquisition (MUGA) scan within 30 days prior to registration
* Zubrod (Eastern Cooperative Oncology Group \[ECOG\]) Performance Status of 0-2 within 14 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (within 14 days prior to registration)
* Platelets \>= 100,000 cells/mm\^3 (within 14 days prior to registration)
* Hemoglobin \>= 9.0 g/dL (within 14 days prior to registration)
* HER2-positive cohort: Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 9.0 g/dL is acceptable
* HER2-low expressing cohort: Note: Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (granulocyte colony-stimulating factor \[G-CSF\]) is not allowed
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance (CrCl) \>= 30 mL/min by the Cockcroft-Gault formula (within 14 days prior to registration)
* HER2-positive cohort: Total bilirubin =\< 1.5 x ULN (within 14 days prior to registration) (Not applicable to patients with known Gilbert's syndrome) (within 14 days prior to registration)
* HER2-positive cohort: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x ULN (within 14 days prior to registration)
* HER2-low expressing cohort: Total bilirubin ≤ 1.5 x ULN if no liver metastases; or \< 3 x ULN in the presence of documented Gilbert's Syndrome or liver metastases (within 14 days prior to registration) (within 14 days prior to registration)
* HER2-low expressing cohort: AST and ALT ≤ 3 x ULN if no liver metastases; or \< 5 x ULN with liver metastases (within 14 days prior to registration)
* HER2-low expressing cohort: Serum albumin ≥ 2.5 g/dL (within 14 days prior to registration)
* Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial. Testing is not required for entry into protocol
* For patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g., patients immunized against hepatitis B)
* For patients with a known history of hepatitis C virus (HCV) infection, they 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
* Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* Willing to use highly effective contraceptives for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 7 months following last dose of study drug; this inclusion is necessary because the treatment in this study may be significantly teratogenic. Women must refrain from donating eggs during this same period
* Men with partners of childbearing potential must be willing to use a highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner, and to continue the use of contraception for the duration of study treatment and for at least 7 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the pregnancy. Men must refrain from donating sperm during this same period
* Prior to registration, patients who have had chemotherapy or palliative-intent radiotherapy must have all toxicities related to prior treatment recovered to ≤ grade 1
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
* HER2-positive cohort: Prior systemic therapy for the study cancer in the unresectable or recurrent and/or metastatic disease setting
* Note: Prior chemotherapy for a different cancer is allowed; prior androgen receptor targeted therapy in any setting is allowed; prior systemic therapy, including HER2-directed therapies given as neoadjuvant therapy, adjuvant therapy, and/or concurrently with radiation is allowed
* HER2-low expressing cohort: HER2 directed therapy for unresectable or recurrent or metastatic disease is not allowed
* Severe, active co-morbidity defined as follows:
* Unstable angina requiring hospitalization in the last 6 months
* Myocardial infarction within the last 6 months
* New York Heart Association Functional Classification III/IV (Note: 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.)
* Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing
* Patient must not have an active infection requiring IV antibiotics, antivirals, or antifungals
* HER2-positive cohort only: \>= grade 3 peripheral neuropathy
* Interstitial lung disease or pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on chest CT scan
* Any hemorrhage or bleeding event grade \>= 3 within 28 days prior to registration
* History of allergic reactions to compounds of similar chemical or biologic composition to: HER2-positive cohort: ado-trastuzumab emtansine, trastuzumab, and/or docetaxel (or any of their excipients). HER2-low expressing cohort: DS-8201a (trastuzumab deruxtecan), trastuzumab
* History of exposure to the following cumulative doses of anthracyclines:
* Doxorubicin or liposomal doxorubicin \> 500 mg/m\^2
* Epirubicin \> 900 mg/m\^2
* Mitoxantrone \> 120 mg/m\^2
* Note: If another anthracycline, or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of doxorubicin 500 mg/m\^2
* HER2-low expressing cohort only: Receipt of live, attenuated vaccine (messenger ribonucleic acid \[mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of DS-8201a (trastuzumab deruxtecan)
* Pregnancy and individuals unwilling to discontinue nursing PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, DRUG: Docetaxel, PROCEDURE: Echocardiography Test, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, OTHER: Questionnaire Administration, BIOLOGICAL: Trastuzumab, BIOLOGICAL: Trastuzumab Deruxtecan, BIOLOGICAL: Trastuzumab Emtansine
Metastatic Salivary Gland Carcinoma, Recurrent Salivary Gland Carcinoma, Stage III Major Salivary Gland Cancer AJCC v8, Stage IV Major Salivary Gland Cancer AJCC v8, Unresectable Salivary Gland Carcinoma
Study of NALIRIFOX in Advanced Unresectable Small Bowel Tumors
Tiago Biachi de Castria, MD, PhD - tiago.biachi@moffitt.org
NCT06835387
Inclusion Criteria:
• Subject has been informed about the nature of the study, and has agreed to participate in the study, and signed the ICF prior to participation in any study-related activities. Also, as determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤ 1 within 28 days prior to registration and within 7 days prior to start of study regimen.
• Histological or cytologically confirmed small bowel adenocarcinoma per AJCC, 9th edition that has not been previously treated in the metastatic setting. Subjects treated in the adjuvant setting who completed treated \> 6 months and do not have residual toxicities \> Grade 1 are eligible. NOTE: Subjects with only localized disease or disease which will likely become resectable after chemotherapy (per investigator discretion) are NOT eligible.
• Mismatch repair proficient (MMRp) and/or microsatellite stable (MSS) disease per institutional standard of care testing.
• Subject has one or more metastatic lesions measurable by CT scan (or MRI, if the subject a. is allergic to CT contrast media) according to RECIST Version 1.1 criteria. Lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration and repeated within 7 days prior of C1D1. * Platelets (Plt) ≥ 100,000 cells/mm3 * Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3; without the use of hemopoietic growth factors * Hemoglobin (Hgb) ≥ 9 g/dL * Calculated creatinine clearance ≥ 30 mL/min; Cockcroft-Gault formula for actual body weight should be used for calculation. For subjects with a body mass index (BMI) \> 30 kg/m2, adjusted body weight should be used instead * Total bilirubin ≤ 1.5 × ULN * Aspartate aminotransferase (AST) ≤ 2 × ULN; \< 5× with liver metastases * Alanine aminotransferase (ALT) ≤ 2 × ULN; \< 5× with liver metastases * Albumin ≥ 2.5 gm/dL * PT and PTT ≤ 1.5 x ULN; subjects on warfarin or other vitamin K antagonists should be discussed with the sponsor-investigator. * Urinalysis: Urinalysis results without clinically significant abnormalities, per the investigator's assessment
• Electrocardiogram (ECG) without any clinically significant findings (QT interval corrected by Fridericia's formula (QTcF) ≤450 msec and no known arrhythmias) and per the investigator's assessment.
• Females of childbearing potential must have a negative urine or serum pregnancy test within ≤ 7 days prior to registration. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception. Males able to father a child who are sexually active with a female of childbearing potential must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception.
• Subjects infected with human immunodeficiency virus (HIV) are eligible if they meet all the following criteria: * CD4 count is ≥350 cells/uL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications; * Probable long-term survival with HIV if cancer were not present; * Stable on a highly active antiretroviral therapy (HAART) regimen for ≥ 4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study; * HIV is not multi-drug resistant; * Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication. NOTE: Testing is not required at screening unless mandated by local policy.
• Subjects with known chronic hepatitis B virus (HBV) infection, must have an undetectable HBV viral load on suppressive therapy, if indicated. Subjects with a history of hepatitis C virus (HCV) infection must have been treated and cured. For subjects with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. NOTE: Testing is not required at screening unless mandated by local policy.
Exclusion Criteria:
• Adenocarcinoma originating in the ampulla or appendix (duodenal tumors that involve the ampulla but originate in the duodenum are eligible).
• Neuroendocrine or any other histology different than adenocarcinoma.
• Prior treatment with irinotecan.
• Prior treatment of SBA in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy: * Palliative radiotherapy is permitted but lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable. * Placement of biliary stent/tube is permitted.
• Known history of central nervous system (CNS) metastases. (subjects on a stable or decreasing dose of steroids and deemed clinically stable as per the investigator's assessment are eligible).
• Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhea \> Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction.
• Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
• History of any second malignancy in the last 2 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years prior to screening. Subjects who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are eligible.
• Known hypersensitivity to any of the components of nanoliposomal irinotecan, other liposomal products, or any components of 5-FU, LV or oxaliplatin.
• Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including: * Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before screening * High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year prior to screening * New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or an unexplained fever \>38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled), which in the investigator's opinion might compromise the subject's participation in the study or affect the study outcome.
• Major surgery, other than diagnostic surgery, within 4 weeks prior to consent.
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1. Subjects are ineligible if: * they are unable to discontinue the use of strong inhibitors of CYP3A, CYP2C8 and UGT1A1 at least 1 week prior to consent; * they are unable to discontinue the use of strong CYP3A and CYP2C8 inducers at least 2 weeks prior to consent;
• There is presence of any contraindications outlined in the Contraindications or Warnings and Precautions sections of the IB for nanoliposomal irinotecan, or in the prescribing information for 5-FU, LV or oxaliplatin.
• Subjects who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.
• History of systemic connective tissue disorders (e.g. lupus, scleroderma, arteritis nodosa).
• Subjects who have received a live vaccine within 4 weeks prior to consent.
• History of the following: interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies, and peripheral artery disease (e.g. claudication, Leo Buerger's disease).
• Known low or absent dihydropyridine dehydrogenase (DPD) activity. This is not mandatory but where required by local regulations, testing for DPD deficiency must be performed using a validated method which is recommended by local health authorities.
DRUG: Nanoliposomal irinotecan, DRUG: Oxaliplatin, DRUG: 5 fluorouracil, DRUG: Leucovorin
Small Bowel Adenocarcinoma
Health indicators, training, and performance among ultra-endurance athletes
Alexandra Lempke - alexandra.lempke@vcuhealth.org
Alexandra Lempke
HM20031840
HM20031840
Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator (CARVTOP-ICD)
Mehmet Aktas, M.D. - Mehmet_Aktas@URMC.Rochester.edu
NCT06964464
Inclusion Criteria:
* Age ≥ 18 years
* ICD implanted for primary prevention for HFrEF (either ICM or NICM) with remote monitoring capability
* Current treatment with metoprolol succinate and willing to switch to carvedilol
* LVEF \<50% during the past 12 months prior to consent
Exclusion Criteria:
* Unwilling or unable to follow the protocol
* Treatment with any other ßB than metoprolol succinate or no ßB treatment
* Known prior intolerance or contraindication to carvedilol
* Systolic blood pressure \<100 mmHg
* Enrollment in another clinical trial
* Inability or unwilling to consent DRUG: Metoprolol Succinate, DRUG: Carvedilol
Heart Failure With Reduced Ejection Fraction (HFrEF), Sudden Cardiac Death, Ventricular Arrhythmia, Implantable Cardioverter Defibrillator (ICD), Beta-blocker Therapy, Cardiomyopathy
arrhythmia, heart failure, ICD, implantable cardioverter defibrillator, ICD shock, carvedilol, metoprolol succinate, beta-blocker
Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea
Alexandra Lempke - Alexandra.Lempke@vcuhealth.org
NCT06533865
Inclusion Criteria:
For FHA and controls:
* Female, age 14-30 years, skeletally mature with bone age ≥ 14 years (only 2% of growth left)
* For women of reproductive age, agree to use an effective non-hormonal contraceptive method or a progestin releasing intrauterine device (no evidence of systemic skeletal effects) for the study duration
* Biochemical criteria:
* Negative βHCG (pregnancy test)
* TSH within twice the upper limit of normal; potassium, magnesium within the normal range; prolactin \<10 ng/mL above the upper limit of normal; FSH not elevated.
* Serum ALT ≤ 3 times upper limit of normal, LDL ≤ 190 mg/dl
* eGFR ≥ 30ml/minute
* If the diagnosis of FHA is unclear, we may check additional labs (e.g., testosterone and sex hormone binding globulin if there is a suspicion of PCOS based on clinical hyperandrogenism).
Additional inclusion criteria for FHA:
* Less than 3 menses in the preceding 6 months
* BMD Z-score ≤ -1.0 at ≥ 1 skeletal site (for subjects \<18 years old, we will use the height Z-score-adjusted BMD Z-score using the pediatric bone density calculator developed by the National Institutes of Health and currently maintained by the Children's Hospital of Philadelphia)
* Dental check-up within the past year
* If the menstrual status of the subject is unclear due to the presence of a progestin-releasing IUD, serum estradiol levels will be checked twice, at least one week apart. Both estradiol levels must be \< 50 pg/mL.
Exclusion Criteria:
For FHA and controls
* Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus
* Use of bisphosphonates
* Use of other medications known to affect bone metabolism within 3 months of the study (other than calcium and vitamin D supplementation).
* Current use of systemic corticosteroids
* Migraine with aura.
* Personal history of or first-degree relative with unprovoked thromboembolism (unless the subject has been tested and ruled out for a hypercoagulable state).
* Active substance use disorder; current smoker
* History of malignancy or Paget disease of bone
* Pregnant, planning to become pregnant within 12 months after the end of treatment and/or breastfeeding
Additional exclusion criteria for FHA
* Cardiovascular: History of myocardial infarction or stroke; history of hypertension or use of anti-hypertensive medications
* Immunodeficiency or taking immunosuppressive therapy
* Other conditions that can cause oligo-amenorrhea such as PCOS, primary ovarian insufficiency
* Dental: Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (tooth extraction, dental implants, oral surgery in the past 3 months), poor oral hygiene, periodontal and/or pre-existing dental disease
* Planned invasive dental procedure or other planned major surgery for 18 months after the baseline visit
* Known sensitivity or absolute contraindication to any of the products or components of the medications to be administered (romosozumab, zoledronic acid, transdermal estradiol, micronized progesterone, calcium or vitamin D supplements)
* Concerning EKG findings for ischemia
Additional exclusion criteria for normal-weight healthy controls
• BMD Z-score \<-2.5 (who we will refer for evaluation) DRUG: Romosozumab, DRUG: Placebo, DRUG: Zoledronic acid
FHA (Functional Hypothalamic Amenorrhea)
Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma
ctrrecruit@vcu.edu
NCT06860594
Inclusion Criteria:
* Patients must have histologically, molecularly, or cytologically confirmed recurrent astrocytic tumors including:
* GBM or variants, IDH-wildtype, grade 2-4 (standard curative measures available or not)
* Astrocytoma, IDH-mutant, grade 2-4 (standard curative measures available or not)
* Diffuse midline gliomas, including pediatric-type H3 G34 or E3 K27 mutant tumors.
* Tumors ≤ 6 cm in maximal diameter.
* Patients who had recent resection for recurrent tumor must have measurable disease.
* Patients must have at least a 6-month break from last dose of radiation therapy.
Re-irradiation within 6 months may increase risk for radiation necrosis/edema, which will affect toxicity assessment and patient safety. Additionally, GBM and other high-grade astrocytic tumors can exhibit pseudo-progression within 6 months from completing definitive, 1st line radiation therapy, and re-irradiation during this period will increase risk for misattribution of effect.
* Prior history of standard dose radiation for gliomas of 59.4-60 gray (Gy) in 1.8-2 Gy per fraction (or equivalent or lower) is allowed.
* Patients who received non-standard radiation dose regimen (e.g., 40 Gy, 34-35 Gy, 25 Gy) or stereotactic radiosurgery are eligible as long as there is at least one of the following:
* A new tumor outside the original radiotherapy field as determined by the investigator.
* There is histologic confirmation of tumor on biopsy or resection.
* Imaging findings are consistent with true progressive disease (on standard MRI sequences, MRI spectroscopy/perfusion, or nuclear medicine imaging).
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of triapine in patients \< 18 years of age, children are excluded from this study.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%).
* Absolute neutrophil count ≥ 1,500/mcL.
* Hemoglobin ≥ 8 g/dL.
* Platelets ≥ 100,000/mcL.
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional ULN.
* Creatinine ≤ 1.5 x ULN OR glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with 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 II or better.
* Patients must be able to swallow whole capsules.
* Patients must be able to undergo MRIs with contrast. Patients with non-compatible devices with MRI can be eligible if CT scans of sufficient quality are obtained. However, patients without non-compatible devices may not use CT scans to meet this requirement.
* The effects of triapine on the developing human fetus are unknown. For this reason and because ribonucleotide reductase (RNR) inhibitor agent and radiation are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 12 months after finishing study treatment. People of child-bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 2 weeks of registration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 12 months after completion of triapine administration.
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria:
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia.
* Patients who are receiving any other investigational agents.
* Patients who are actively taking medications that are known to induce methemoglobinemia (e.g. sulfonamides, nitrofurans, anti-malarials \[primaquine, chloroquine\], cyclophosphamide, and ifosfamide).
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine.
* Patients with known G6PD deficiency. Testing for G6PD deficiency is not required.
* Patients with uncontrolled intercurrent illness, active infections, or any other significant condition(s) that would make participation in this protocol unreasonably hazardous.
* Pregnant women are excluded from this study because triapine is a RNR inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with triapine, breastfeeding should be discontinued if the mother is treated with triapine. These potential risks may also apply to the radiation used in this study. PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, DRUG: Triapine
Astrocytoma, IDH-Mutant, Grade 2, Recurrent Adult Diffuse Hemispheric Glioma, H3 G34-Mutant, Recurrent Adult Diffuse Midline Glioma, H3 K27-Mutant, Recurrent Astrocytoma, IDH-Mutant, Recurrent Astrocytoma, IDH-Mutant, Grade 3, Recurrent Astrocytoma, IDH-Mutant, Grade 4, Recurrent Glioblastoma, IDH-Wildtype
Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
Medical Information - medinfo@eidostx.com
NCT06563895
Key
Inclusion Criteria:
* Male or female ≥ 18 to ≤ 75 years of age inclusive.
* Participants must have an established genotype (hetero- or homozygosity) of a TTR gene variant that is known to be pathogenic (eg, V30M/p.V50M, V122I/p.V142I, T60A/p.T80A, or any other pathogenic TTR variant(s)) confirmed by central laboratory prior to randomization.
* Participant's age is no more than 10 years (≤ 10) younger than the PADO.
Key Exclusion Criteria:
* Evidence of ATTR-CM or ATTR-PN.
* Presence of a TTR variant known to be phenotypically protective (eg, T119M, R104H).
* Current or past treatment with other TTR modifying therapies.
* Contraindication to or inability to undergo Cardiac magnetic resonance testing.
* Major organ dysfunction, including: kidney disease, liver disease, heart disease (including cardiomyopathy), neuropathy
* Other diseases or conditions such has cancer within 3 years, untreated hyperthyroidism or hypothyroidism, type 1 diabetes, active hepatitis B or C, HIV.
* Major surgery within the past 3 months or planned during the next 12 months.
* Known hypersensitivity to acoramidis. DRUG: Acoramidis, DRUG: Placebo oral tablet
Amyloidosis, Amyloid Cardiomyopathy, Transthyretin Amyloidosis, Cardiomyopathies, Heart Diseases, Polyneuropathies
Amyloidosis, ATTR-CM, ATTR-PN, Transthyretin, Amyloid, TTR
Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib (POIESIS)
John Mei - jmei@kartosthera.com
NCT06479135
Inclusion Criteria for Ruxolitinib Alone Period:
* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
* High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* JAK-inhibitor treatment naive
Exclusion Criteria for Ruxolitinib Alone Period:
* Prior Splenectomy
* Splenic irradiation within 3 months prior to the first dose
* Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
* Eligible for Bone Marrow Transplant
* Peripheral blood or bone marrow blast count ≥ 10 percent
Inclusion Criteria for Randomized Period:
* PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
* ECOG performance status of 0 to 2
* Treatment with a stable dose of ruxolitinib
* Suboptimal response to run-in ruxolitinib treatment
Exclusion Criteria for Randomized Period:
* Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 × 10\^9/L
* Peripheral blood or bone marrow blast count ≥ 10 percent
DRUG: Navtemadlin, DRUG: Navtemadlin placebo, DRUG: Ruxolitinib
Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis, Primary Myelofibrosis, MF
Navtemadlin, KRT-232, Ruxolitinib, POIESIS, TP53, Suboptimal response, Sub-optimal response
A Study to Evaluate the Safety and Efficacy of MK-3120 in Participants With Advanced Solid Tumors (MK-3120-002)
Toll Free Number - Trialsites@msd.com
NCT06818643
Inclusion Criteria:
* Has a confirmed advanced (unresectable and/or metastatic) solid tumor and has received or been intolerant to all available treatments
* If human immunodeficiency virus (HIV) positive, has well controlled HIV on antiretroviral therapy (ART)
* If hepatitis B surface antigen (HBsAg) positive, must have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load
* If hepatitis C virus (HCV) infected, must have undetectable HCV viral load
Exclusion Criteria:
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has uncontrolled significant cardiovascular disease or cerebrovascular disease
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has pleural effusion, ascites, and/or pericardial effusion that are symptomatic or require repeated drainage
* Is HIV-positive and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Known additional malignancy that is progressing or has required active treatment within the past 2 years
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Active infection requiring systemic therapy, with exceptions
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has HBV or HCV infection BIOLOGICAL: MK-3120
Advanced Solid Tumors, Malignant Neoplasm
A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com - Clinical.Trials@bms.com
NCT06481306
Inclusion Criteria
\- Cohort A.
i) Healthy male and female (who are not of childbearing potential) participants, as determined by the investigator based on medical history and other determinations. Females not of childbearing potential must have been amenorrhoeic for at least 12 months without an alternative medical cause and have follicle-stimulating hormone (FSH) levels of at least 40 IU/L or have undergone a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
ii) Body mass index (BMI) of 18.0 to 32.0 kg/m\^2, inclusive. BMI = weight (kg)/ (height \[m\])\^2 as measured at screening.
iii) No evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory assessments beyond what is consistent with the target population.
\- Cohort B.
i) Participants with a documented diagnosis of Sickle Cell Disease (SCD) with genotype HbSS, HbSβ0-thal, or HbSβ+-thal.
ii) Participants with ≥ 4 vaso-occlusive crises (VOCs) within the previous 12 months or ≥ 2 VOCs within the previous 6 months.
iii) Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
iv) Must have the following laboratory values:.
A. Hemoglobin ≥ 5.5 and ≤ 12 g/dL (males) or ≥ 5.5 and ≤ 10.6 g/dL (females).
B. Absolute neutrophil count ≥ 1500/μL.
C. Platelet count ≥ 100 × 10\^3/μL.
D. Absolute reticulocyte count \> 100 × 10\^3/μL or \> 50 × 10\^3/μL if taking hydroxyurea.
Exclusion Criteria
\- Cohort A.
i) Any significant medical condition or any condition that confounds the ability to interpret data from the study.
ii) Participant has any condition, including the presence of laboratory abnormalities, that places the participant at unacceptable risk if the participant was to participate in the study.
iii) Any major surgery or planned surgery (except GI surgery) within 12 weeks of the first study intervention administration.
\- Cohort B.
i) Participants with any condition, including significant acute or chronic medical illness, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
ii) Participants with more than 6 severe VOCs defined as VOCs requiring ≥ 24 hours of hospital admission within 12 months prior to the first dose of study intervention or any VOC requiring ≥ 24 hours of hospital admission within 30 days prior to the first dose of study intervention.
iii) Participants with any episode of acute chest syndrome within the last 6 months prior to the first dose of study intervention.
iv) Creatinine clearance (CrCl) \< 60 mL/min/1.72m2 using Chronic Kidney Disease Epidemiology (CKD-EPI) equation
* Cohort A and B.
i) Participant is receiving regularly scheduled RBC or platelet transfusions or has received a RBC transfusion within 28 days and a platelet transfusion within 14 days prior to starting treatment with BMS-986470.
* Other protocol-defined Inclusion/Exclusion criteria apply.
DRUG: BMS-986470, DRUG: Placebo, DRUG: Famotidine
Anemia, Sickle Cell, Healthy Volunteers
Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial
ctrrecruit@vcu.edu
NCT05327010
Inclusion Criteria:
* Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
* Patients must have a tumor lesion that can be biopsied with 'low' or 'minimal' risk and at least one measurable disease site, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
* Note: Tumor lesions that are situated in a previously irradiated area may or may not be considered measurable
* Patients in cohorts 1, 2, and 4 should have at least one relevant mutation. Patients enrolled in cohorts 1-3 do not require that PARP inhibitor (i) be the immediate prior therapy to be eligible for the trial. Patients should sign a screening consent that will allow the review of local next generation sequencing (NGS) or equivalent Clinical Laboratory Improvement Amendment (CLIA)-certified assay results by MD Anderson's Precision Oncology Decision Support (PODS) team to ensure that the mutations are actionable. No variants of uncertain significance (VUS) will be allowed
* Patients in Cohort 1 must have (i) a germline or somatic mutation in BRCA1 or BRCA2; and (ii) must have received prior PARPi monotherapy or PARPi combination-therapy
* Patients in Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: BARD1; FANCA; BRIP1; PALB2; RAD51; RAD51C; RAD51D, with no evidence of mutations in BRCA1 or BRCA2; and (ii) must have received prior PARPi monotherapy or PARPi combination therapy
* Patients in Cohort 3 must be (i) patients who have had PR/CR on prior PARPi monotherapy or PARPi combination treatment; and (ii) patients with no evidence of BRCA1 or BRCA2 mutations or any of the relevant DDR aberrations listed in cohort 2. Patients with ovarian cancer should not have progressed on platinum-therapy within six months of therapy
* Patients in Cohort 4 must have KRAS mutated advanced solid tumors. Prior treatments with KRAS inhibitors are permitted. Patients with KRAS G12C mutations must have already had KRAS G12C targeted therapy (e.g., sotorasib) previously
* Patients must have received at least one line of systemic therapy in the advanced/metastatic setting. Subjects with diseases without known effective options, and subjects who have declined standard of care therapy prior to study introduction, are also eligible. Patients with ovarian cancer in cohort 3 should not have progressed on platinum within six months of therapy
* Age \>= 18 years
* Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with talazoparib in patients \< 18 years of age, children are excluded from this study
* Patients must be greater than 4 weeks (6 weeks for nitrosoureas or mitomycin C) beyond treatment with any chemotherapy or other investigational therapy including hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation. Patients must have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities =\< grade 1) with the exception of alopecia or anorexia
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 150,000/mcL
* Hemoglobin \>= 10.0 g/dL (no blood transfusions in the preceding 28 days)
* Total bilirubin 1.5 x =\< institutional upper limit of normal (ULN) OR direct bilirubin = ULN for subjects with total bilirubin levels \> 1.5 x ULN
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN
* Creatinine 1.5 x institutional ULN OR glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 for subjects with creatinine levels \> 1.5 x institutional ULN, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable viral load while on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable. Patients with known symptomatic brain metastases requiring steroids are excluded. Of note, patients who required a single dose of corticosteroids on days receiving radiation treatment do not require a 2-week washout. Follow-up brain imaging after central nervous system (CNS)-directed therapy must show no evidence of progression and patient should be clinically stable for at least 1 month. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
* 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. However, patients with concurrent malignancy that is progressing or requiring active treatment are excluded
* 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 of class 2B or better
* The effects of the combination ZEN003694 (ZEN-3694) and talazoparib on the developing human fetus are unknown. For this reason, and because BET inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 7 months after completion of study drug administration
* Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test unless prior tubal ligation (\>/= 1 year before screening), total hysterectomy, or menopause (defined as 12 consecutive months of amenorrhea)
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) or talazoparib
* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or P-gp, strong inhibitors of BCRP, sensitive substrates of CYP1A2, proton-pump-inhibitors (H2 antagonists are allowed), and herbal medications/preparations (vitamins are allowed) are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 (ZEN-3694). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is a BET inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 1 month following the last dose of the study drug. These potential risks may also apply to other agents used in this study
* Patients who are involved in the planning and/or conduct of the study
* Patients who are unable or unwilling to swallow pills
* Active infection requiring intravenous (IV) antibiotics, or other uncontrolled intercurrent illness requiring hospitalization
* Patients receiving any medications or substances that are factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed
* Patients with radiation to \> 25% of the bone marrow
* Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694 (ZEN-3694) or talazoparib
* Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor
* Patients with cerebrovascular accident (CVA), myocardial infarction, or unstable angina within 6 months prior to the first dose of ZEN003694 (ZEN-3694) or talazoparib
* Patients with impairment of gastrointestinal function that may significantly alter the absorption of ZEN003694 (ZEN-3694) or talazoparib
* Patients that have had major surgery other than diagnostic surgery, dental surgery, or stenting within 4 weeks prior to the first dose of ZEN003694 (ZEN-3694) or talazoparib DRUG: BET Bromodomain Inhibitor ZEN-3694, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Diagnostic Imaging Testing, DRUG: Talazoparib
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
Strategy for Improving Stroke Treatment Response (SISTER)
Rebeca Aragon Garcia, BS, CCRC - aragonra@ucmail.uc.edu
NCT05948566
Inclusion Criteria:
• Age 18 years and older
• Suspected anterior circulation acute ischemic stroke
• NIH Stroke Scale score ≥4 prior to randomization a. The participant must have a clearly disabling deficit if NIHSS is 4-5.
• Favorable baseline neuroimaging consisting of all of the following:
• ASPECTS of 6 or more on CT (or ASPECTS of ≥7 on MRI)
• Favorable perfusion imaging on CT perfusion (CTP)/MR-perfusion weighted imaging (PWI) consisting of all of the following: i. Mismatch ratio of penumbra: core \>1.2 ii. Mismatch volume \>10 cc iii. Core \<70 cc c. If CT hypodensity is present, then in the investigator's visual assessment, the total acute infarct volume combined area of (a) the CT hypodensity and (b) the perfusion-based core volume (CBF\<30%) should be smaller than perfusion-based volume (area of Tmax\>6s minus CBF\<30%).
• Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well.
• Able to receive assigned study drug within 120 minutes of qualifying perfusion imaging. \*
• Informed consent for the study participation obtained from participant or their legally authorized representatives. * Study drug administration is encouraged within 90 minutes after qualifying perfusion image but is allowed up to 120 minutes. After 120 minutes, another perfusion image to ensure that inclusion criteria are met is required.
Exclusion Criteria:
• Received endovascular treatment with clot engagement.
• Patients who undergo groin puncture but clot engagement is not attempted due to spontaneous distal migration are permitted to be enrolled in the trial if all other eligibility criteria are met.
• Patients who undergo groin puncture but clot is not engaged due to reasons other than spontaneous distal migration are NOT permitted.
• Received or planned to receive intravenous thrombolysis.
• Pre-stroke modified Rankin score \>2.
• Previous treatment with TS23 or known previous allergy to antibody therapy.
• Known pregnancy, women who are breastfeeding or plan to breastfeed within 3 months of receiving TS23 or have a positive urine or serum pregnancy test for women of childbearing potential.
• Known previous stroke in the past 90 days.
• Known previous intracranial hemorrhage, intracranial neoplasm, subarachnoid hemorrhage, or arterial venous malformation.
• Known active diagnosis of intracranial neoplasm.
• Clinical presentation suggestive of a subarachnoid hemorrhage, even if initial CT scan was normal.
• Surgery or biopsy of parenchymal organ in the past 30 days.
• Known trauma with internal injuries or persistent ulcerative wounds in the past 30 days.
• Severe head trauma in the past 90 days.
• Persistent systolic blood pressure \>180mmHg or diastolic blood pressure \>105mmHg despite best medical management.
• Serious systemic hemorrhage in the past 30 days.
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with International Normalized Ratio (INR) \>1.7.
• Platelets \<100,000/mm3.
• Hematocrit \<25 %.
• Elevated aPTT above laboratory upper limit of normal.
• Creatinine \> 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine.
• Received the following within the previous 24 hours:
• If patient received unfractionated heparin within the last 24 hours, the patient must have an aPTT within normal range prior to enrollment.
• Low molecular weight heparins such as Dalteparin, enoxaparin, tinzaparin in full dose within the previous 24 hours.
• Received Factor Xa inhibitors (such as Fondaparinux, apixaban or rivaroxaban) within the past 48 hours.
• Received direct thrombin inhibitors (e.g., argatroban, dabigatran, bivalirudin, desirudin, lepirudin) within 48 hours.
• Received glycoprotein IIb/IIIa inhibitors within the past 14 days.
• Known pre-existing neurological or psychiatric disease which would confound the neurological/functional evaluations.
• Current participation in another research drug treatment protocol (i.e., participants could not start another experimental agent until after 90 days).
• Concurrent acute myocardial infarction, pulmonary embolism, deep venous thrombosis or other thrombotic event that requires anticoagulation or anti-platelet treatment.
BIOLOGICAL: TS23
Ischemic Stroke
CLEOPATTRA: A Research Study to Look at the Effects of Treatment With a Medicine Called Coramitug (NNC6019-0001) in People With Heart Failure Due to Transthyretin Amyloid (ATTR) Amyloidosis (CLEOPATTRA)
Novo Nordisk - clinicaltrials@novonordisk.com
NCT07207811
Inclusion Criteria:
* Male or female.
* Age 18 years or above at the time of signing the informed consent.
* Have an established diagnosis of ATTR-CM (wild-type ATTR \[ATTRwt\] or variant ATTR \[ATTRv\]), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF.
Note: Target ATTRv recruitment is approximately 15 percent of the study population.
• Cardiac amyloid infiltration demonstrated by: * Cardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) scintigraphy with single-photon emission computed tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE). Notes: * Non-invasive diagnostic pathway will be confirmed by a centralised expert review. * Bone tracer scintigraphy will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP).
• Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm).
• Chronic HF (New York Heart Association \[NYHA\] Class I-IV) requiring ongoing treatment with a loop diuretic with: * At least 1 documented hospitalisation for HF, OR * History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema). * Expected to be on stable cardiovascular medical therapy (defined as no greater than 50 percent dose adjustment and no categorical changes of medications), with the exception of diuretics, 4 weeks prior to the randomisation visit. * Completed more than 50 meters on the 6MWT at screening.
Exclusion Criteria:
* Known or suspected hypersensitivity to study intervention(s) or related products.
* Current or previous participation (dosing with active treatment) in a study for an investigational ATTR depleting drug or ATTR gene editing therapy.
* Total bilirubin greater than 3 times the upper limit of normal (ULN) at screening.
* Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis, known leptomeningeal amyloidosis, or multiple myeloma.
* HF not primarily caused by ATTR-CM (e.g., due to hypertension, valvular heart disease, or ischemic heart disease in the opinion of the investigator).
* Currently hospitalised or hospitalised within 14 days prior to screening.
* Currently treated with positive inotropic medication.
* Uncorrected, severe, haemodynamically significant, left-sided heart valve disease.
Note: Pre-existing echocardiogram up to 2 years old may be used.
* Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 60 days of screening.
* Prior solid organ transplant or planned solid organ transplant during the study.
* Left ventricular ejection fraction (LVEF) less than 30 percent as assessed by centralised review of echocardiography.
* Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, carcinoma in situ/high-grade prostatic intraepithelial neoplasia \[PIN\], low-risk prostate cancer, or on stable therapy for prostate cancer) within 3 years before screening.
* End-stage renal disease (estimated glomerular filtration rate \[eGFR\] less than 15 mL/min/1.73 m\^2 at screening, or chronic/intermittent haemodialysis or peritoneal dialysis). DRUG: NNC6019-0001, DRUG: Placebo (NNC6019-0001)
Transthyretin Amyloid Cardiomyopathy (ATTR CM)