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PREVENT ALL ALS Study
ALL ALS Patient Navigator - info@all-als.org
NCT06581861
Inclusion Criteria:
• Age 18 years or older
• Capable of providing informed consent
• Willing to follow study procedures
• First-degree relative of a known carrier of any ALS causative gene1 (regardless of whether ALS or FTD has actually been symptomatic in the family) OR First-degree relative of an individual with ALS and/or FTD in a family with a "compelling family history" of ALS/FTD, regardless of whether genetic testing has occurred in symptomatic family members. A "compelling family history" is defined as a pedigree with at least 2 close relatives who had ALS or FTD, with at least one of those family members having had ALS.
• Access to a smartphone, computer, or tablet, and internet (need not be in the home - access to a public library or other available computer with internet connection is sufficient)
Exclusion Criteria:
• Evidence of neurological signs or symptoms concerning for ALS of FTD, at the discretion of the site investigator which will be communicated to the applicant along with referral for appropriate clinical follow-up.
• Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, active suicidal ideation, suicide attempt, or untreated major depression \<= 90 days (about 3 months) of screening, which in the opinion of the Investigator would interfere with the study procedures
• Clinically significant, unstable medical condition (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, malignant and potentially progressive cancer) that would render the participant unlikely to be able to complete 12 months of follow-up, according to Investigator's judgment Exclusion Criteria for Participants Undergoing Optional Lumbar Puncture
• Medically unable to undergo lumbar puncture (LP) as determined by the site investigator (i.e., bleeding disorder, a skin infection at or near the LP site, known or suspected intracranial or intraspinal tumor or other cause of increased intracranial pressure).
• Allergy to Lidocaine or other local anesthetic agents.
• Use of anticoagulant medication or antiplatelet medications (aside from aspirin 81 mg) that cannot be safely withheld prior to lumbar puncture.
• Blood dyscrasia, abnormal bleeding diathesis, or the use of dialysis for renal failure.
• Current pregnancy based on participant self-report
• Clinical judgement of the site investigator that the participant would be unable to undergo multiple lumbar punctures. Inclusion Criteria for Genetic Testing Results Sub-study
• Age 18 years of age or older
• Capable of providing informed consent
• Willing to follow study procedures
• Currently enrolled in the PREVENT ALS Study
Amyotrophic Lateral Sclerosis
ALS, Amyotrophic Lateral Sclerosis, Biomarker, Observational, at-risk
Automated Robotic TCD in Traumatic Brain Injury (ART-TBI)
Shraddha Mainali, MD - shraddha.mainali@vcuhealth.org
NCT05848297
Inclusion Criteria:
* Adults ≥18
* Blunt TBI with Glasgow Coma Score (GCS) ≤8
* Injury within 72 hours
* Adequate TCD windows
* Ability to obtain informed consent from a Legally Authorized Representative (LAR)
Exclusion Criteria:
* Catastrophic brain injury with grim prognosis (e.g.: GCS 3 with bilateral mid-position pupil)
* C- spine fracture with evidence of spinal cord injury
* Severe skull or scalp injury precluding device placement
* Planned decompressive hemicraniectomy
* Continuous fever for \>6 hours at the time of enrollment (despite treatment)
* Lack of TCD window DEVICE: Transcranial Doppler ultrasonography (TCD)
Brain Injuries, Traumatic
The Rhythm Evaluation for AntiCoagulaTion With Continuous Monitoring of Atrial Fibrillation (REACT-AF)
Anna Baranova - anna.baranova2@vcuhealth.org
NCT05836987
Inclusion Criteria:
• 22-85 years of age.
• English speaking participants. Spanish-only speakers may be included in the future at select sites appropriately translated.
• History of non-permanent atrial fibrillation.
• CHA2DS2-VASC score of 1-5 for men and 2-5 for women without prior stroke or Transient Ischemic Attack (TIA), The CHA2DS2-VASc score is a point-based system used to stratify the risk of stroke in Atrial Fibrillation (AF) patients. The acronym CHA2DS2-VASc stands for congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female). Congestive heart failure defined as: The presence of signs and symptoms of either right (elevated central venous pressure, hepatomegaly, dependent edema) or left ventricular failure (exertional dyspnea, cough, fatigue, orthopnea, paroxysmal nocturnal dyspnea, cardiac enlargement, rales, gallop rhythm, pulmonary venous congestion) or both, confirmed by non-invasive or invasive measurements demonstrating objective evidence of cardiac dysfunction and/or ejection fraction \< 40%.
• The participant is on a DOAC at the time of screening and willing to stay on DOAC for duration of study.
• Willing and able to comply with the protocol, including: * Possession of a smart watch-compatible smart phone (iPhone that supports the latest shipping iOS) with a cellular service plan * Be willing to wear the smart watch for the suggested minimum of 14 hours a day * Expected to be within cellular service range at least 80% of the time
• Willing and able to discontinue DOAC
• The participant is willing and able to provide informed consent.
Exclusion Criteria:
• Valvular or permanent atrial fibrillation.
• Current treatment with warfarin and unwilling or unable to take a DOAC.
• The participant is a woman who is pregnant or nursing.
• The participant is being treated with chronic daily oral NSAIDs and is unwilling or unable to discontinue use for the study duration. Use of low-dose aspirin is permitted.
• Existing cardiac rhythm device or indication for a permanent pacemaker, Implantable Cardioverter-Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) device or planned insertable cardiac monitor. Insertable cardiac monitors are permitted unless they are being used to guide anticoagulation treatment.
• Known or suspected symptomatic or asymptomatic atrial fibrillation lasting ≥ 1 hour/month over the last 3 months.
• Any documented single AF episode lasting ≥ 1 hour on a cardiac monitor performed within 90 days prior to randomization.
• Ablation for AF within the last 2 months.
• Prior or anticipated left atrial appendage occlusion or ligation.
• Mechanical prosthetic valve(s) or severe valve disease.
• Hypertrophic cardiomyopathy.
• Participant needs DOAC for reasons other than preventing stroke or arterial embolism resulting from AF (i.e., preventing Deep Vein Thrombosis (DVT) or PE) or needs permanent OAC (i.e., congenital heart defects, prosthetic heart valve).
• Participants deemed high risk for non-cardioembolic stroke (i.e., significant carotid artery disease defined as stenosis \> 75%) based on the investigator's discretion.
• The participant is enrolled, has participated within the last 30 days, or is planning to participate in a concurrent drug and/or device study during the course of this clinical trial. Co-enrollment in concurrent trials is only allowed with documented pre-approval from the study manager; there is no concern that co-enrollment could confound the results of this trial.
• The participant has a tattoo, birthmark, or surgical scar over the dorsal wrist area on the ipsilateral side that the AFSW may be worn.
• The participant has a tremor on their ipsilateral side that the AFSW may be worn.
• Any concomitant condition that, in the investigator's opinion, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).
• Known hypersensitivity or contraindication to direct oral anticoagulants.
• Documented prior stroke (ischemic or hemorrhagic) or transient ischemic attack.
• Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism). AF ablation does not constitute reversible AF.
• \> 5% burden of premature atrial or ventricular depolarizations on pre-enrollment cardiac monitoring.
• History of ECG-documented, sustained atrial flutter that has not been treated with ablation (participants with atrial flutter who have been ablated are eligible for enrollment)
• Stage 4 or 5 chronic kidney disease.
• Conditions associated with an increased risk of bleeding: * Major surgery in the previous month * Planned surgery or intervention in the next three months that would require cessation of anticoagulation \> 2 weeks. * History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intra- articular bleeding * Gastrointestinal hemorrhage within the past year unless the cause has been permanently eliminated (e.g., by surgery) * Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days * Hemorrhagic disorder or bleeding diathesis * Need for anticoagulant treatment for disorders other than AF * Uncontrolled hypertension (Systolic Blood Pressure \>180 mmHg and/or Diastolic Blood Pressure \>100 mmHg)
DEVICE: AFSW Guided DOAC, DRUG: Continuous DOAC therapy
Atrial Fibrillation
Atrial Fibrillation, Anticoagulation, AF-sensing Smart Watch, Ischemic Stroke, Systemic Embolism
Ribociclib And Endocrine Treatment of Physician's Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (RaPhLRR)
Oana Danciu, MD - ocdanciu@uic.edu
NCT05467891
Eligibility Criteria to Collect Optional Correlative Blood and Tissue at Local Recurrence
* Written informed consent (stage I) and HIPAA authorization for release of personal health information obtained prior to performing any study-specific procedures. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
* Male or female age ≥ 18 years at the time of consent.
* Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory.
* Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample. If there is insufficient tissue from the most recently collected sample, earlier tissue may be used on a case-by-case basis if permission is granted by the sponsor investigator.
* Patient has locoregional recurrence of breast cancer: locoregional recurrence is defined as invasive recurrence in the ipsilateral breast, axilla, regional nodes, or chest wall.
Inclusion Criteria for Treatment Phase:
Subject must meet all of the following applicable inclusion criteria to participate in this study:
* Written informed consent (stage II/ main consent) and HIPAA authorization for release of personal health information obtained prior to performing any study-specific screening procedures. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
* Male or female age ≥ 18 years at the time of consent. NOTE: Both pre- and post-menopausal women are eligible. Post-menopausal status is defined as:
* Prior bilateral oophorectomy
* Age ≥60
* Age \<60 and amenorrhea for the last 12 or more months(in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range.
* ECOG Performance Status of 0-1 within 28 days prior to registration.
* If patient is receiving tamoxifen or toremifene, a washout period of 5 half-lives (i.e. 35 days) prior to registration is required (during that period the participant can take AI).
* Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory.
* Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample. If there is insufficient tissue from the most recently collected sample, earlier tissue may be used on a case-by-case basis if permission is granted by the sponsor investigator.
* Patients have had adequate local treatment for locoregional recurrence (LRR) of breast cancer.
* Locoregional recurrence is defined as recurrence in the ipsilateral breast, axilla, regional lymph nodes, or chest wall.
* Local treatment is defined as either surgery, radiation therapy, or a combination of both if indicated.
* Adequate local therapy is surgery with negative microscopic margins. Radiation therapy is mandated for patients with microscopically involved margins and recommended for all patients who had not received radiotherapy as part of their primary treatment.
* Patients who have distant metastatic disease will not be eligible.
* Prior treatment with neoadjuvant and adjuvant chemotherapy and ET is allowed.
* Patients must enroll within 6 months of the last local treatment, either local surgery or radiation; or systemic chemotherapy (if patient is receiving chemotherapy), whichever occurred last. Chemotherapy after local therapy is allowed. ET for recurrent disease is allowed for up to 12 months prior to enrollment.
* Patient has no contraindication to the adjuvant ET in the trial and is planned to be treated or continue treatment with ET.
* Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
* Hematological
* Absolute Neutrophil Count (ANC): ≥ 1.5 x 109/L
* Platelets: ≥ 100 x 109/L
* Hemoglobin (Hgb): ≥ 9.0 g/dL
* Renal
---Estimated glomerular filtration rate (eGFR): ≥ 30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula
* Hepatic
* Bilirubin: ≤ upper limit of normal (ULN) except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN
* Aspartate aminotransferase (AST): ≤ 2.5 × ULN except for patients with liver metastasis, who are only included if the AST is \< 5 × ULN
* Alanine aminotransferase (ALT): ≤ 2.5 × ULN except for patients with liver metastasis, who are only included if the ALT is \< 5 × ULN
* Coagulation
---International Normalized Ratio (INR) : ≤ 1.5 × ULN (unless is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug)
* Electrolytes ---Potassium, Magnesium, and Total Calcium (corrected for serum albumin): Within normal limits or corrected to within normal limits with supplements.
* Standard 12-lead ECG values defined as
* QTcF interval at screening \< 450 msec (QT interval using Fridericia's correction)
* Resting heart rate 50-90 bpm (determined from the ECG)
* Females of childbearing potential who are sexually active with a male able to father a child must have a negative pregnancy test (serum or urine) within 14 days prior to registration and must be willing to use a highly effective method of contraception that does not contain estrogen and/or progesterone. See the protocol for definition of childbearing potential.
* 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.
* Ability to swallow and retain oral medication.
Exclusion Criteria for Treatment Phase:
Subjects meeting any of the criteria below may not participate in the study:
* Patient with a known hypersensitivity to any of the excipients of ribociclib.
* Patient who has received prior CDK4/6 inhibitor for recurrent disease. Patients who received a CDK4/6 inhibitor in the adjuvant setting may participate if they have been off therapy for at least 1 year prior to diagnosis of recurrent disease.
* Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
* Pregnant or breastfeeding or planning to become pregnant during the trial (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
* Patients with distant metastases of breast cancer beyond regional lymph nodes as defined by AJCC (8th edition).
* Treatment with any investigational drug within 30 days prior to registration or participation in any other type of medical research judged not to be scientifically or medically compatible with this study. Enrollment or planned enrollment in another study that does not involve an investigational drug will be allowed at the discretion of the treating investigator.
* Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
* Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol: (e.g., chronic pancreatitis, chronic active hepatitis, HIV, active untreated or uncontrolled fungal, bacterial or viral infections, etc.). Testing to be done at investigator's discretion.
* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
* History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
* Documented cardiomyopathy
* History of Left Ventricular Ejection Fraction (LVEF) \< 50%
* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
* Risk factors for Torsades de Pointe (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
* Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g., within 5 half-lives or 7 days prior to starting study drug)
* Inability to determine the QTcF interval
* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
* Systolic Blood Pressure (SBP) \>160 or \<90 mmHg
* Patient is currently receiving any of the following substances and cannot be discontinued 7 days prior to Cycle 1 Day 1:
* Concomitant medications, herbal supplements, and/or fruits (e.g., grapefruit, pummelos, star fruit, Seville oranges) and their juices that are strong inducers or inhibitors of CYP3A4/5,
* Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
* Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: a short duration (\<5 days) of systemic corticosteroids; any duration of topical applications (e.g. for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
* Patient with an uncontrolled psychiatric condition that, in the investigator's judgment, may cause unacceptable safety risks, impede research integrity and compliance, or interfere with the objectives of the study.
DRUG: Ribociclib, DRUG: Fulvestrant, DRUG: Anastrozole, DRUG: Letrozole, DRUG: Exemestane
Locoregional Recurrence, Hormone Receptor-positive Breast Cancer, HER2-negative Breast Cancer
A Study of the Drug Letermovir as Prevention of Cytomegalovirus Infection After Stem Cell Transplant in Pediatric Patients
ctrrecruit@vcu.edu
NCT05711667
Inclusion Criteria:
* \>= 2 years and \< 18 years at the time of enrollment
* Weight must be \>= 6 kg at the time of enrollment
* Planned allogeneic HCT (bone marrow, peripheral blood stem cell, or cord blood transplant)
* Patient must be CMV sero-positive (i.e., recipient CMV immunoglobulin G positive)
* Note: If a patient has hypogammaglobulinemia but has previously been documented as CMV sero-positive, that is acceptable for study inclusion. For all patients already confirmed to be CMV IgG seropositive, repeat testing is not required within 7 days prior to enrollment. However, the laboratory data determining eligibility must be available in the patient's medical/research record for verification
* Patient is eligible for entry only if it is feasible for plasma CMV PCR testing to be sent and resulted within the protocol mandated time period
* Reminder: To limit the likelihood of positive plasma CMV PCR post-enrollment and prior to start of study treatment period, it is recommended that patient enrollment proceed after patients start their transplant preparative regimen
* Patient must have a performance status corresponding to Lansky/Karnofsky scores \> 50
* Note: Use Lansky for patients =\< 16 years of age and Karnofsky for patients \> 16 years of age. For further reference, see performance status scales scoring under the standard sections for protocols among protocol reference materials provided on the Children's Oncology Group (COG) member website: https://members.childrensoncologygroup.org/prot/reference\_materials.asp
* Estimated glomerular filtration rate \> 10 mL/min/1.73 m\^2 and not receiving dialysis
* Direct bilirubin =\< 2 mg/dL and serum glutamate-pyruvate transaminase (SPGT) (alanine transaminase \[ALT\]) =\<10 x upper limit of normal (ULN) for age
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
Exclusion Criteria:
* Expected inability to tolerate oral formulation of letermovir
* Hypersensitivity to letermovir or any component of the formulation
* History of CMV end organ disease within 6 months (180 days) prior to enrollment
* Note: CMV end organ disease based on proposed definitions by Ljungman et al. and inclusive of proven, probable or possible disease
* Receipt of prior allogeneic HCT within one year of study enrollment
* Planned prophylactic administration of other anti-CMV medications or cellular products during the study, including:
* High dose acyclovir (defined as doses \>= 1500 mg/m\^2 IV or \>= 3200 mg oral (patients \>= 40 kg) or \>= 2400 mg/m\^2 (patients \< 40 kg) per day)
* High dose valacyclovir (defined as doses \>= 3000 mg/day in patients \> 20 kg)
* Foscarnet
* Ganciclovir
* Valganciclovir
* CMV-directed cytotoxic T lymphocytes
* Planned receipt of the following contraindicated medications during the study treatment period; contraindicated medications must be discontinued at least 14 days prior to Day +1
* Contraindicated medications for all patients:
* Pimozide
* Ergot alkaloids
* Contraindicated medications for patients planned to receive cyclosporine:
* Bosentan
* Pitavastatin
* Simvastatin
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted in certain animal reproduction studies with letermovir. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active female patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their letermovir treatment and through at least 4 weeks after the last dose of letermovir.
* Note: No contraception measures are needed specifically during letermovir treatment for male trial participants who have pregnant or non-pregnant female partner(s) of reproductive potential. Contraception measures may be required for other aspects of the HCT procedure.
* 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 PROCEDURE: Biospecimen Collection, DRUG: Letermovir
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
A Research Study to Advance the CF Therapeutics Pipeline for People Without Modulators
Olena Boyarska - olena.boyarska@seattlechildrens.org
NCT06504589
Consent
A. Written informed consent (and assent when applicable) obtained from participant or participant's legal guardian
B. Is willing and able to adhere to the study visit schedule and other protocol requirements
Demographics
A. ≥ 12 years of age at Visit 1
Medical History
A. For persons of child-bearing potential: must not be pregnant at Visit 1 or plan to get pregnant during the 12-month study period
Disease History
A. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
* Sweat chloride ≥ 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)
* Two well-characterized disease-causing pathogenic variants in the CFTR gene
or
* One well-characterized disease-causing mutation and a second CFTR variant (with variable or uncharacterized disease-causing potential) and sweat ≥ 30 mmol/liter with permission of the study sponsor-investigators
B. Clinically stable with no significant changes in health status within the 28 days prior to and including Visit 1
C. Does not have a history of lung transplantation
Concomitant Medications
A. Not genetically eligible for a CFTR modulator according to product label indications and/or No use of CFTR modulator for 28 days prior to Visit 1 with no intent to start or restart during the study period
B. No use of an investigational drug within 90 days prior to and including Visit 1
C. Not currently participating in an interventional drug or device trial. Participation in long-term safety follow-up studies (without redosing) and/or behavioral intervention trials is allowed.
D. No initiation of new chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, Cayston®) within 28 days prior to and including Visit 1
E. No acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 28 days prior to and including Visit 1
Cystic Fibrosis
ineligible and/or not taking CFTR modulators, People with CF
Testing the Use of Chemotherapy After Surgery for High-Risk Pancreatic Neuroendocrine Tumors
ctrrecruit@vcu.edu
NCT05040360
Inclusion Criteria:
* Participants must have a histologic diagnosis of well-differentiated pancreatic neuroendocrine tumor (pNET) that was resected between 14 and 120 days prior to registration. Participants must have a scan within 90 days prior to registration without evidence of metastatic disease. Acceptable scans are multiphase computed tomography (CT) abdomen, magnetic resonance imaging (MRI) with intravenous (IV) contrast of the abdomen, or positron emission tomography (PET)-CT DOTATATE imaging if the DOTATATE PET-CT included IV iodine contrast for the CT portion of the exam
* Resection must have been an R0 or R1 per treating investigator's assessment and/or pathology report
* Ki-67 testing, which is considered part of standard of care in the pathology report, must have been performed between 14 and 90 days prior to registration and the result must be \>= 3% and =\< 55%. Treating investigators are encouraged to contact the S2104 Study Chairs and/or the study pathology chair with questions. If more than one Ki-67 is reported (e.g., primary tumor versus lymph node or metastatic site), the highest one should be considered for the study eligibility criteria
* Participants with localized resected pNETS must have a Zaidi score of \>= 3 derived by the following factors and points:
* 1 point; symptomatic tumor defined as one of the following:
* Gastrointestinal bleed
* Jaundice
* Gastrointestinal obstruction
* Pain from primary tumor prior to surgical resection
* Pancreatitis
* 2 points; primary pancreas tumor size \> 2 cm
* 1 point; Ki-67 3% to 20%
* 1 point; lymph node positivity = 1
* 6 points; Ki-67 21% to 55%
* Participants may have received resection/ablation of liver oligo-metastatic disease (up to 5 liver metastases) at the time of well-differentiated pNET resection
* Participants must have recovered from effects of surgery as determined by the treating investigator
* Participants must be \>= 18 years old
* Participants must have Zubrod performance status of 0-2
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Leukocytes \>= 3 x 10\^3/uL (within 28 days prior to registration)
* Absolute neutrophil count \>= 1.5 x 10\^3/uL (within 28 days prior to registration)
* Platelets \>= 100 x 10\^3/uL (within 28 days prior to registration)
* Total bilirubin =\< institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional ULN (within 28 days prior to registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 28 days prior to registration)
* Serum creatinine =\< 1.5 x institutional ULN (within 28 days prior to registration)
* Calculated creatinine clearance \>= 50 ml/min (within 28 days prior to registration)
* Participants must be able to swallow pills
* Participants must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol
* No other active malignancy or history of prior malignancy is allowed, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
* 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
Exclusion Criteria:
* Participants must not have unresected or unablated metastatic disease
* Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis
* Participants must not have received prior neoadjuvant therapy for treatment of pancreatic neuroendocrine tumor. Use of somatostatin analogs prior to surgery is permitted
* Participants must not have received somatostatin analogs after surgery
* Participants must not be planning to receive warfarin while on protocol treatment. Other anticoagulants are allowed
* Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine
* Participants must not have known absorption issues that would limit the ability to absorb study agents
* Participants must not have had an arterial thromboembolic event, unstable angina, or myocardial infarction within 12 months prior to registration
* Participants must not have active or uncontrolled infection
* Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator
* Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen DRUG: Capecitabine, DRUG: Temozolomide
Metastatic Malignant Neoplasm in the Liver, Pancreatic Neuroendocrine Tumor, Stage I Pancreatic Neuroendocrine Tumor AJCC v8, Stage II Pancreatic Neuroendocrine Tumor AJCC v8, Stage III Pancreatic Neuroendocrine Tumor AJCC v8
Addition of Antibiotics to Upfront Treatment Regimen for Colorectal Cancer
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06728072
Inclusion Criteria:
* Diagnosis of stage IV colorectal cancer
* Measurable disease by Response evaluation criteria in solid tumors (RECIST) 1.1 criteria
* Planned first-line treatment with a 5FU-based doublet chemotherapy regimen for colon cancer, specifics of the regimen at the discretion of the treating physician Note: Patients who have received adjuvant therapy \>6 months prior are eligible
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
* Absolute neutrophil count (ANC) ≥1,500 cells/μL
* Platelet count ≥100,000 cells/μL
* Hemoglobin ≥8 g/dL Note: The use of transfusion or other intervention to achieve hemoglobin ≥8 g/dL is acceptable.
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) Note: Patients with documented liver metastases: AST and ALT ≤5 × ULN
* Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥40 mL/min using the Cockcroft-Gault equation: (140 - age) × body weight/plasma creatinine × 72 (× 0.85 if female)
* Radiographically measurable disease by RECIST 1.1
* Nonpregnant and not actively breastfeeding
* Sexually active patients of childbearing potential and their partners must agree to use medically acceptable form of contraception, per treating investigator, throughout the study Patients should continue to use medically acceptable methods of contraception after study treatment ends, following the guidance for their specific chemotherapy regimen.
Childbearing potential excludes:
Age \> 50 years and naturally amenorrhoeic for \> 1 year OR previous hysterectomy or bilateral salpingo-oophorectomy
* Patients on a pre-existing daily aspirin regimen may participate in the study without interrupting this regimen.
* Patients with a contraindication to aspirin may participate in the study. These patients will not be required to take aspirin as part of the study treatment.
Exclusion Criteria:
* Total colectomy
* Diagnosed with Cockayne Syndrome
* Using disulfiram, tizanidine, or theophylline and unable to stop taking these medications for the length of the microbiome modulation therapy
* On methotrexate doses of 15 mg/week or more
* History of allergic reaction to ciprofloxacin, metronidazole, or aspirin
* Fuss course of antibiotics in the 30 days before chemotherapy start Note: Full course is defined as ≥5 doses with an intent to treat a defined infection. Use of antibiotics intended for prophylaxis at the time of surgery is allowed
* Corrected QT interval (QTc) \>480 on baseline ECG
* Diagnosed with a malabsorptive syndrome
* Inability to swallow tablets DRUG: Standard of Care Chemotherapy + Metronidazole, ciprofloxacin, aspirin
Colorectal Cancer, CRC
Colorectal Cancer, CRC
A Single-session Intervention Adaptation of the Habit Framework for the Prevention of Eating Disorders
Courtney Breiner - breinerc@vcu.edu
NCT06861608
Inclusion Criteria:
* EAT-26 score ≥ 20 ( EAT-26, participants will meet the "referral criteria" which includes a score of 20 or more or meeting frequency criteria on bingeing, purging, laxative/diuretic use, and/or exercise.)
* English-language fluency, self-reported3
* Access to a phone, tablet, or computer
Exclusion Criteria:
* Failure to correctly complete one of the attention checks in the survey prior to the intervention
* Failure to correctly complete both anagram tasks in the survey prior to the intervention
* Completion of the screening survey or pre-intervention surveys in an improbably fast time BEHAVIORAL: Screening Questionnaire, BEHAVIORAL: Pre-Intervention Questionnaires (~10 minutes), BEHAVIORAL: SSI (Single-session intervention (~30 minutes) Active arm, BEHAVIORAL: SSI (Single-session intervention (~30 minutes) control arm, BEHAVIORAL: End-of-Intervention Questionnaires (~5 minutes)
Eating Disorder Not Otherwise Specified
prevention of eating disorders
Safety and Tolerability Study of GIM-531 in Advanced Solid Tumors
Jayadev Sureddi, CBCC CRO - jayadev.sureddi@cbcc.global
NCT06425926
Key
Inclusion Criteria:
* Written informed consent
* Cytologically or histologically confirmed locally advanced or metastatic solid tumor that has progressed on standard therapy or for which no standard therapy exist; or be intolerant of standard therapy
* Have not received an experimental drug within 4 weeks or 5 half-lives (whichever is shorter) of study drug treatment or already be enrolled in a clinical study
* ECOG performance status 0-1
* Laboratory and ECG assessments within 28 days of enrollment including acceptable cardiac, renal, and hepatic functions
* Agree to baseline core needle biopsy or archival (within 12 months of screening) tumor submission; Note: Participants whose only site(s) of disease are in areas considered moderate or high risk for biopsy complications may be enrolled without a fresh biopsy upon Sponsor approval.
* Non pregnant participants; female participants of child bearing potential with non-sterile partners agree to use an effective form of contraception from the time of first dose of study drug (or 14 days prior to first dose for oral contraception) until 7 months after the last dose of study drug. Effective forms of contraception include hormonal (injection or oral), double barrier method, or intrauterine device. Non-sterile male participants with sexual partners of childbearing potential agree to use a barrier contraception method and agree to not donate sperm from the time of first dose of study drug until 4 months after the last dose of study drug.
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
Phase 1 Expansion Cohorts Specific Inclusion Criteria (in addition to above inclusion criteria):
* NSCLC: Participants must have locally advanced/unresectable or metastatic NSCLC. Participants must have received no more than 3 prior lines of therapy in the advanced/metastatic setting.
* TNBC: Participants must have locally advanced unresectable, recurrent, or metastatic TNBC. Participants must have received no more than 3 prior lines of therapy in the advanced/metastatic setting.
* Ovarian Cancer: Participants must have locally advanced unresectable, recurrent, or metastatic ovarian cancer. Participants must have platinum-resistant ovarian cancer defined as disease recurrence or within 6 months after the last administration of platinum-based chemotherapy. Participants must have received no more than 1 line of therapy after development of platinum resistance. Maintenance treatment with Poly(ADP-ribose) polymerase inhibitors (PARPi) or bevacizumab are not counted as separate lines of therapy.
* Tumors with AKT3 mutation/amplification: Participants must have a locally advanced unresectable, recurrent, or metastatic solid malignancy. Participants with known AKT3 mutation/amplification based on next generation sequencing (NGS) performed per local standard of care.
Phase 2 Specific Inclusion Criteria (in addition to above inclusion criteria):
* Have confirmed unresectable Stage III or metastatic Stage IV cutaneous melanoma, NSCLC, or RCC that has radiographically progressed (as confirmed by imaging assessed by the Investigator) on an approved single-agent or combination anti-PD-1 therapy
* Must have received the anti-PD-1 therapy containing regimen as the latest line of treatment and be eligible to restart or to continue anti-PD-1 therapy in combination with GIM-531
* BRAF wild-type melanoma or RCC: Participants must have received no more than 2 prior lines of therapy in the advanced/metastatic setting
* BRAF (V600) mutant melanoma or NSCLC: Participants must have received no more than 3 prior lines of therapy in the advanced/metastatic setting.
Key Exclusion Criteria:
* Ongoing \>Grade 1 toxicity from prior therapy according to Common Terminology Criteria for Adverse Events v5.0 (Note: Grade 2 alopecia and Grade 2 sensory neuropathy are not exclusionary)
* Has known leptomeningeal disease, spinal cord compression, or brain metastases, except participants with the following:
* Brain metastases that have been treated and are clinically stable for at least 4 weeks prior to the first administration of study drug; Note: Participants receiving steroids for brain metastases must be either off steroids or on a stable, or decreasing dose, of \<10 mg daily of prednisone (or equivalent) in order to be eligible for enrollment; and
* No ongoing neurological symptoms related to the anatomic location of the brain metastases.
Note: Neurological symptoms that are considered sequelae to treatment for brain metastases are allowed.
* Has known structural cardiac disease
* Has known serious arrythmia, serious dysrhythmia, history of long QT syndrome, or clinically relevant cardiac conduction abnormalities
* Has an active autoimmune disease that has required systemic treatment in the past 12 months (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
* At time of screening, is receiving systemic steroid therapy (greater than or equal to 10 mg/day of prednisone or equivalent) or is taking any immunosuppressive therapy; Note: Use of topical, inhaled, nasal, or ophthalmic steroids is allowed.
* Has active and clinically significant bacterial, fungal, or viral infection, including known hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
* Has a history of, or currently has, an acquired or primary (congenital) immunodeficiency;
* Has had prior anti-cancer treatment with chemotherapeutic agents or immune modulating agents within \<4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study drug.
* Has received a live vaccine within 30 days of first dose of study drug;
* Has had or has planned major surgery within 2 weeks of the first dose of study drug;
* Inability to swallow an oral dose of a medication (eg, oral capsules)
* Is taking medications that are considered strong inducers or inhibitors of CYP2C8 or CYP3A4/5, P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), or sensitive substrates of P-gp and BCRP (Appendix C) that cannot be discontinued at least 1 week prior to first dose of study drug and for the duration of the study.
* Is taking drugs that modify gastric pH, such as proton-pump inhibitors (PPIs) or H2 blockers. Antacids such as calcium carbonate or aluminum hydroxide-based products are permitted. DRUG: GIM-531, DRUG: Anti-PD-1 monoclonal antibody
Melanoma Stage IV, Solid Tumor
PD-1 resistance, PD-1 resistant/refractory, AKT3
Left vs Left Randomized Clinical Trial
Mihail G Chelu, MD, PhD - leftvsleft@bcm.edu
NCT05650658
Inclusion Criteria:
* Men and women 18 years of age or older.
* A LVEF ≤ 50% within 6 months prior to enrollment.
* Resting QRS duration ≥130 ms as evidenced by a historical 12-lead ECG prior to enrollment OR anticipated right ventricular pacing \>40% OR device in place with right ventricular pacing \> 40%.
* Are optimized on HF guideline directed medical therapy according to current HF published guidelines OR patient's physician will make an effort to start all guideline-directed medical therapy and titrate doses up as permitted by the participant clinical status and co-morbidities prior to implantation procedure.
Exclusion Criteria:
* Women who are pregnant, lactating, or plan to become pregnant during the course of the trial.
* Participants with angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary, intervention in the next three (3) months.
* Enzyme-positive myocardial infarction within the past three (3) months prior to enrollment.
* Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past three (3) months prior to enrollment.
* Reversible non-ischemic cardiomyopathy (e.g., acute viral myocarditis).
* Participants with Chagas disease, cardiac sarcoidosis or amyloidosis.
* Expected to receive left ventricular assist device or heart transplantation within 6 months.
* Participants with primary severe valvular disease (e.g., aortic stenosis).
* Have a life expectancy of less than 12 months.
* Participants with irreversible brain damage from preexisting cerebral disease.
* Participants with a contrast dye allergy unable or unwilling to undergo pretreatment with steroids and/or diphenhydramine.
* Participants participating in any other interventional cardiovascular clinical trial.
* Participants who would be unable to comply with the study's follow-up visit schedule; or
* Participants who had any prior unsuccessful attempt at implantation of biventricular pacing (BiVP), His Bundle Pacing (HBP), or Left Bundle Branch Pacing (LBBP) device. DEVICE: His/LBBP, DEVICE: BiVP
Heart Failure, Heart Failure With Reduced Ejection Fraction, AV Block, LBBB, RBBB, Intraventricular Conduction Delay, Pacing-Induced Cardiomyopathy
Patient-reported Outcomes of Donor Site Healing Using Different Palatal Protection Techniques
Rafael Amorim Cavalcanti de Siqueira - amorimcavalr@vcu.edu
NCT06892496
Inclusion Criteria:
* At least 18 years of age
* Healthy or Mild controlled systemic diseases with no functional limitations (ASA I or ASA II)
* Sites with 1 to 3 teeth or implants requiring soft-tissue grafting
* Minimum palatal thickness of 2 mm
* Willing to participate and sign an informed consent
Exclusion Criteria:
* Patients with systemic conditions that could impair wound healing (i.e. diabetes, immunosuppressive, chemotherapy, etc.)
* Pregnant patients
* Patients with bleeding disorders or taking anticoagulants
* Smokers
* Patients with a history of palatal graft harvesting OTHER: Visual Analog scale (VAS) questionnaire, OTHER: Vacuum-formed retainer (VFR) technique, OTHER: 3-D printed acrylic resin stent (3DS) technique, OTHER: Flowable resin composite stent (FRC) technique, OTHER: Photographs of the patient's palate, OTHER: Measuring graft dimensions, OTHER: Chairside Polymer Stent
Mucosal Erosion, Gingival Recession
soft tissue graft, pain, wound healing, CPS: Chairside polymer stent
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com - Clinical.Trials@bms.com
NCT04094610
Key
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
Inclusion Criteria:
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
Inclusion Criteria:
• Cohort Specific
Inclusion Criteria:
* Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
* Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
* Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
DRUG: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma, Primary CNS Tumors
ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
ctrrecruit@vcu.edu
NCT02523014
* Documentation of disease:
* Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review
* Molecular documentation: Presence of SMO, PTCH1, NF2, CDKN2A, AKT1, PIK3CA, PTEN mutations, CDKN2A copy number loss, CDK4, CDK6, CCND1, CCND2, CCND3, or CCNE1 copy number gain in tumor sample as documented specifically by the central laboratory, regardless of whether prior genotype testing outside of the central laboratory was performed
* Progressive OR residual disease, as defined by the following:
* Residual measurable disease: residual measurable disease immediately after surgery without requirement for progression; for grade I disease, progression pre-operatively needs to be documented, with an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 25 months; for patients with SMO/PTCH1 mutations enrolling to receive vismodegib, the change can occur between scans separated by up to 25 months; residual measurable disease will be defined by bidimensionally measurable lesions with clearly defined margins by MRI scans, with a minimum diameter of 10 mm in both dimensions
* Progressive measurable disease: progression defined as an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 25 months
* Post radiation patients: patients with measurable and progressive meningioma who have received radiation are potentially eligible, but need to show evidence of progressive disease after completion of radiation; if the progressive meningioma lesion has been radiated, at least 24 weeks must have elapsed from completion of radiation to registration; if the progressive lesion is outside of the radiation field, then an interval of at least 2 weeks must have elapsed from completion of radiation to registration
* Measurable disease: measurable disease is defined by a bidimensionally measurable main lesion on MRI or computed tomography (CT) images (MRI preferred) with clearly defined margins and a minimum diameter of 10 mm in both dimensions; multifocal disease is allowed
* Prior treatment
* Prior medical therapy is allowed but not required
* No limit on number of prior therapies
* No chemotherapy, or other investigational agents within 28 days prior to registration
* No other concurrent investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study; additionally, no cases of nitrosourea or mitomycin C within 6 weeks prior to registration
* For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval \> 4 weeks must have elapsed from completion of radiation therapy to registration; if the progressive lesion is outside of the radiation field, then an interval of at least 2 weeks must have elapsed from completion of radiation to registration
* Steroid dosing stable for at least 4 days
* Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue
* No craniotomy 28 days prior to and after registration
* Not pregnant and not nursing:
\* A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* For patients with NF2/CDKN2A/AKT1/PIK3CA/PTEN mutation, CKDN2A copy number loss, or CDK4/CDK6/CCND1/CCND2/CCND3/CCNE1 copy number gain: Age \>= 18 years
* For patients with SMO/PTCH1 mutation: Age \>= 30 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Patient history:
* Patients with history of neurofibromatosis (NF) may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months
* No metastatic meningiomas (as defined by extracranial meningiomas outside of CNS) allowed; spinal meningiomas are allowed
* No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug
* No known active hepatitis B or C
* No current Child Pugh class B or C liver disease
* No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)
* No uncontrolled hypertension defined as blood pressure (BP) \> 140/90
* No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration
* No major surgery within 28 days prior to registration for any patients with AKT1/PIK3CA/PTEN mutations receiving capivasertib
* For patients going on to receive capivasertib (i.e. enrolled after Update #08)
* Patients should not have any of the following cardiac criteria:
* Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram (EKG) (e.g., complete left bundle branch block, third degree heart block)
* Any factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, potential for Torsade de Pointes, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
* Experience any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) class \>= II
* Uncontrolled hypertension (systolic blood pressure \[SBP\] \< 90 mmHg and/or diastolic blood pressure \[DBP\] \< 50 mmHg)
* Cardiac ejection fraction outside institutional range of normal or \< 50% (whichever is higher) as measured by echocardiogram (or multigated acquisition \[MUGA\] scan if an echocardiogram can't be performed or is inconclusive); left ventricular ejection fraction (LVEF) below lower limit of normal for site
* Patients should not have any of the following criteria:
* With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of registration
* Hemoglobin \< 9 g/dL (\< 5.59 mmol/L); note: any blood transfusion must be \>= 14 days prior to the determination of a hemoglobin \>= 9 g/dL (\>= 5.59 mmol/L)
* Proteinuria 3+ on dipstick analysis or \> 500 mg/24 hours
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of capivasertib
* History of hypersensitivity to active or inactive excipients of capivasertib or drugs with a similar chemical structure or class to capivasertib
* Current disease or condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
* Previous allogeneic bone marrow transplant
* Known immunodeficiency syndrome
* Concomitant medications (only regarding NF2/CDKN2A/CDK4/CDK6/CCND1/CCND2/CCND3/CCNE1/AKT1/PIK3CA/PTEN genetic alterations):
* Chronic concomitant treatment with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors must discontinue the drug for 14 days prior to registration on the study for patients with NF2 mutation enrolled to GSK2256098, as well as for patients with AKT1/PIK3CA/PTEN mutations enrolled to capivasertib
* For NF2 patients going on to receive GSK2256098 and for patients with AKT1/PIK3CA/PTEN mutations enrolled to capivasertib: concomitant treatment with strong CYP3A4 inducers or CYP2D6 substrates is not allowed; patients must discontinue the drug 14 days prior to registration
* For NF2 patients going on to receive abemaciclib: avoid concomitant use of CYP3A inducers and strong CYP3A inhibitors; use caution with coadministered moderate or weak CYP3A inhibitors
* Diabetic status:
* For patients with NF2 or SMO/PTCH1 mutations: No uncontrolled diabetes defined as a known diabetic with HBA1C \> 7.5 OR fasting glucose \> 140 mg/dL.
* For patients with AKT1/PIK3CA/PTEN mutations:
* Glycosylated hemoglobin (HbA1C) \< 8.0% (63.9 mmol/mol)
* No type 1 diabetes mellitus
* No requirement for insulin for routine diabetic management and control
* No requirement for more than two oral hypoglycemic medications for routine diabetic management and control
* Patients with a pre-existing diagnosis of type 2 diabetes mellitus must have fasting glucose \< 9.3 mmol/L (167mg/dL); fasting is defined as no caloric intake for at least 8 hours
* Patients without a pre-existing diagnosis of type 2 diabetes mellitus must have fasting glucose =\< 7.0 mmol/L (126 mg/dL); fasting is defined as no caloric intake for at least 8 hours
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine OR =\< 1.5 mg/dl x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \> 50 mL/min
* Urine protein:creatinine ratio (UPC) =\< 45 mg/mmol
* Total bilirubin =\< 1.5 x upper limit of normal (ULN); except in case of Gilbert's disease
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
* Sodium, potassium, total calcium (corrected for serum albumin) \& phosphorus within normal limits per institutional guidelines
* QTcF \< 450 msec (QT calculated using Fridericia formula)
* Mean resting heart rate (determined from EKG) 50-100 beats per minute (BMP) (must be obtained from 12-lead EKG defined by a triplicate EKG for patients assigned to the capivasertib arm; patients assigned to all other arms will require a single EKG
* No uncontrolled medical comorbidities per investigator discretion (e.g. interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: Hemoglobin \>= 8 g/dL
\* Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; initial treatment must not begin earlier than the day after the erythrocyte transfusion
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: Prior Treatment
* Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] grade =\< 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy prior to registration; a washout period of at least 28 days is required between last chemotherapy dose and registration (provided the patient did not receive radiotherapy)
* Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy; a washout period of at least 28 days is required between end of radiotherapy and registration
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: No active bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]); screening is not required for enrollment in the absence of symptoms
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: No personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
DRUG: Vismodegib, DRUG: FAK Inhibitor GSK2256098, DRUG: Capivasertib, DRUG: Abemaciclib
Intracranial Meningioma, Recurrent Meningioma, NF2 Gene Mutation
Research Participation With Transgender and Gender-Diverse Youth
An Pham, MD - an.pham@vcuhealth.org
NCT05927350
Inclusion Criteria:
* Gender identity different then sex assigned at birth
* Between the ages 15-21 years
Exclusion Criteria:
* Gender identity the same as their sex assigned at birth
* Younger than 15 years of age, and older than 21 years of age OTHER: Survey
Transgender Persons
National Liver Cancer Screening Trial (TRACER)
Amit Singal, MD, MS - Amit.Singal@UTSouthwestern.edu
NCT06084234
Inclusion Criteria:
Patient must meet all of the following inclusion criteria:
• Adult patients ages 18-85 with cirrhosis from any etiology or with chronic hepatitis B with a PAGE-B score greater than 9 within 12 months of enrollment
• Patient is eligible for HCC surveillance according to treating physician or by the site investigator
• Able to provide informed consent
• Life expectancy \>6 months (after consent) as determined by the treating provider or site investigator
Exclusion Criteria:
Patient will be excluded for any of the following exclusion criteria:
• Child Pugh C cirrhosis
• History or clinical symptoms of hepatocellular carcinoma or cholangiocarcinoma
• History of solid nodule on baseline ultrasound (i.e., lesion 1cm or greater) within 9 months prior to consent without subsequent diagnostic CT/MRI demonstrating benign nature)
• AFP \>20 ng/mL within 6 months prior to consent, in the absence of a contrast-enhanced CT or MRI within 6 months of AFP (before or after) level demonstrating lack of suspicious liver lesions
• Newly diagnosed LR-3 greater than or equal to 1 cm within 6 months prior to consent
• History of LR-4, LR-5, or LR-M on multi-phase CT or contrast-enhanced MRI within 6 months prior to consent
• Presence of another active cancer besides non-melanomatous skin cancer or indolent cancer under active surveillance (e.g., prostate cancer or renal cell carcinoma) within the 2 years prior to consent
• Patient's provider is planning to use MRI- or CT- based surveillance moving forward
• History of a transjugular intrahepatic portosystemic shunt (TIPS)
• History of Fontan associated liver disease or cardiac cirrhosis
• History of solid organ transplantation
• Actively listed for liver transplantation
• Diagnosis of alcohol-associated hepatitis within 3 months prior to consent
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis within 90 days prior to consent
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples)
• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent
• Known pregnancy at consent
• Active warfarin use
DIAGNOSTIC_TEST: GALAD, DIAGNOSTIC_TEST: Liver Ultrasound with or without AFP
Carcinoma, Hepatocellular, Liver Cancer, Liver Cirrhosis, Hepatitis B
Hepatocellular carcinoma surveillance, GALAD, Alpha Fetoprotein
CRISPR-Edited Allogeneic Anti-BCMA CAR-T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma (CaMMouflage)
Caribou Biosciences - clinicaltrials@cariboubio.com
NCT05722418
Inclusion Criteria:
• Documented diagnosis of relapsed/refractory multiple myeloma (MM) with measurable disease (according to IMWG diagnostic criteria.)
• Received at least 3 prior MM treatment lines of therapy which must include a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody as part of a prior line of therapy, either in monotherapy or in combination.
• Eastern Cooperative Oncology Group performance status grade of 0 or 1.
• Adequate hematologic, renal, hepatic, pulmonary, and cardiac function.
Exclusion Criteria:
• Prior treatment with CAR-T cell therapy directed at any target.
• Autologous stem cell transplant within the last 6 weeks before lymphodepletion.
• Allogeneic stem cell transplant within 6 months before lymphodepletion.
• Known active or prior history of CNS involvement.
• Stroke or seizure within 6 months of signing ICF.
• Seropositive for or history of human immunodeficiency virus.
• Vaccinated with live, attenuated vaccine within 4 weeks prior to lymphodepletion.
• Hepatitis B infection.
• Hepatitis C infection.
• Known life-threatening allergies, hypersensitivity, or intolerance to CB-011 or its excipients.
BIOLOGICAL: CB-011
Relapsed/Refractory Multiple Myeloma
CaMMouflage, Allogeneic, Multiple Myeloma, Relapse Refractory Multiple Myeloma, CAR-T Cells, BCMA, Cell Therapy, Cellular Immuno-therapy, CB11A, CB-011, CB-011A, CAR-T, Anti BCMA, ALLO CAR T
Safety and Effectiveness of Valbenazine as Adjunct Therapy to Botulinum Toxin Injections in Cervical Dystonia
Ananna Zaman - Ananna.Zaman@vcuhealth.org
NCT06771323
Inclusion Criteria:
* Idiopathic CD (neck musculature first and most prominently affected)
* 18-75 years old (participants excluded if their dystonia symptoms began before age 18 as childhood-onset dystonia typically represents a genetic and/or primary generalized form of dystonia)
* Onset of dystonia ≥18 years old, no known hyperkinetic movement disorder-related genetic mutation
* Dystonia severity more than minimal and not very severe as defined by Toronto Western Spasmodic Torticollis Rating Scale-2 Motor Severity (TWSTRS-2-Severity) score ≥ 5 and ≤ 20.
* Stable on botulinum toxin injections last 90 days (BoNT dose change \<10% and patient reported stability of response over last two injection cycles)
* Stable on other neuroactive medications.
Exclusion Criteria:
* History of deep brain stimulation
* History of uncontrolled or untreated depression in the prior 3 months, suicidality, or history of suicide attempts
* History of uncontrolled liver disease or failure
* History of tardive dyskinesia or tardive dystonia
* Currently taking dopaminergic and/or anti-dopaminergic medications including VMAT2 inhibitors or other antipsychotic medications
* Exposure to dopaminergic and/or anti-dopaminergic medications including VMAT2 inhibitors or other antipsychotic medications in the last 30 days -Presence of parkinsonism or other movement disorder other than dystonia on exam -Receiving botulinum toxin injections at a planned frequency other than every 3 months or typically receive injections at intervals \<11 weeks or \>13 weeks -Known history of long QT syndrome or cardiac tachyarrhythmia or any clinically significant cardiac abnormality.
* Prolonged QTc as defined by \> 450 msec for men and \> 470 msec for women DRUG: Valbenazine, DRUG: Placebo
Cervical Dystonia
Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Older Adults w/Adv <50% PD-L1 Non-Small Cell Lung Cancer (NSCLC)
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06731413
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) (either squamous or non- squamous)
* Stage IIIB, IIIC or IV disease OR have recurrent disease and not be candidates for curative treatment such as combined chemo-radiation
* No previous line of treatment in the recurrent or metastatic setting. Neoadjuvant or adjuvant treatment more than 6 months before enrollment is acceptable.
* Age 70 or meeting frailty definition or above at the date of signing informed consent
* Absence of driver mutations that have first line Food and Drug Administration (FDA) approved targeted therapy (biomarker testing is optional for squamous cell)
* PD-L1 tumor proportion score (TPS) of less than 50%
* Eastern Cooperative Oncology Group (ECOG) PS of 0-3
* Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment
* Absolute neutrophil count (ANC) ≥ 1,000/μL
* Platelets ≥ 75,000/μL
* Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion permitted)
* Total bilirubin ≤ 2 x institutional upper limit of normal (ULN)
* Aspartate amino transferase (AST)serum glutamic-oxaloacetic transaminase (SGOT) /alanine aminotransferase (ALT)serum glutamic-pyruvic transaminase (SGPT) ≤ 5.0 × institutional ULN
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Participants with life expectancy of less than 3 months at the time of enrollment
* Has active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, or immunosuppressive drugs)
* Diagnosis of interstitial lung disease
* Creatinine clearance of \<30 mL/min
* Symptomatic, untreated central nervous system (CNS) disease or leptomeningeal disease. Patients with asymptomatic or treated CNS disease are eligible
* Required ongoing use of immunosuppressive medication, including steroids, with the following allowable exceptions:
* Doses less than or equal to the equivalent of prednisone 10 mg daily
* Short courses of steroids that are discontinued prior to enrollment
* Inhaled, intranasal and/or topical steroids
* Dexamethasone taper for treating vasogenic edema associated with CNS disease DRUG: Reduced Dose of Chemotherapy and Immunotherapy
Non-small Cell Lung Cancer, NSCLC, Advanced Non-small Cell Lung Cancer, Metastatic Non Small Cell Lung Cancer
Non-Small Cell Lung Cancer, NSCLC
HPV DNA-Guided Radiotherapy De-intensification of Head and Neck Squamous Cell Carcinoma (HN001)
Song W - UVARADONCClinicalTrials@uvahealth.org
NCT05962242
Inclusion Criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, ≥ 18 years of age
• Pathologically proven diagnosis of squamous cell carcinoma of the oropharynx of any AJCC 8th edition stage.
• Eligible for and planning to receive definitive treatment or adjuvant treatment with radiotherapy.
• Participants who are receiving concurrent systemic anticancer therapy (e.g. chemotherapy or immunotherapy) for oropharyngeal cancer are eligible.
• For participants with T1-2 and N0 disease, chemotherapy is not required for eligibility. Participants may or may not receive chemotherapy per physician discretion.
• For participants with T3-4 and/or N+ disease, chemotherapy is required for eligibility.
• Participants may receive investigational agents with prior approval from the Principal Investigator.
• ECOG Performance Status of 0-2.
• p16 positive HPV as determined by NavDx and immunohistochemistry
• For females of reproductive potential: agreement to use adequate contraception during radiation treatment and for 6 months (or more if applicable based on other medications) after the end of radiation treatment.
Exclusion Criteria:
• Evidence of distant metastatic disease
• Prior history of radiotherapy to the head and/or neck
• Had surgery for oropharyngeal cancer within 8 months of enrollment unless it was an incomplete oncologic surgery. Participant is eligible if the gross tumor was not completely removed.
• Diagnosis of T3-4 and/or N+ disease with no plans to receive concurrent chemotherapy.
• Diagnosis of a current or prior invasive malignancy (except non-melanoma skin cancer) unless the participant has been disease free for at least 3 years.
• Participant is a prisoner
• Known contraindications to head and neck radiation therapy such as ataxia telangiectasia or scleroderma.
• Pregnancy or lactation
• Active or severe co-morbidities as defined by the following:
• Unstable angina and/or congestive heart failure requiring hospitalization up to 180 days before registration
• Transmural myocardial infarction up to 180 days before registration
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Hepatic insufficiency as determined by the treating clinician resulting in clinical jaundice and/or coagulation effects or severe liver dysfunction.
• Acquired immune deficiency syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be slightly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
• Tobacco smoking history of 10 pack years or greater, or ≥ 20 pack years if smoking cessation occurred at least 1 year prior to enrollment
• Current use of antineoplastic drugs for other malignancies.
RADIATION: Radiation Therapy
Squamous Cell Carcinoma of the Oropharynx
Radiation Therapy, Radiotherapy, Head Cancer, Neck Cancer, Low Dose Radiation, HPV
mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
Aishwarya Vijendran - aishwaryav@bsd.uchicago.edu
NCT05677490
Inclusion Criteria:
* Histologic documentation: HER2 negative adenocarcinoma as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines (Bartley et al., Journal of Clinical Oncology \[JCO\] 2017) with known PD-L1 combined positive score (CPS) (any CPS is allowed, but should be known prior to registration)
* Stage: unresectable or metastatic
* Tumor site: esophagus, gastroesophageal junction, or stomach
* Measurable disease or non-measurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No prior systemic treatment for unresectable or metastatic disease
* Prior neoadjuvant or adjuvant cytotoxic chemotherapy or adjuvant immunotherapy is allowed as long as it was completed at least 1 year prior to registration
* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
\* Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =\< 7 days prior to registration is required
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 30 mL/min
* Total bilirubin =\< 1.5 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (in patients with liver metastasis: =\< 5 x ULN if clearly attributable to liver metastases)
* 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 positive for human immunodeficiency virus (HIV) are eligible only if they meet all of the following:
* On effective anti-retroviral therapy
* Undetectable HIV viral load by standard clinical assay =\< 6 months of registration
* No known Gilbert's syndrome or known homozygosity for UGAT1A1\*28 polymorphism
* No baseline grade \>= 2 peripheral neuropathy, neurosensory toxicity, or neuromotor toxicity per CTCAE version (v) 5.0 regardless of causality
* No medical condition such as uncontrolled infection or uncontrolled diabetes mellitus which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* No untreated, symptomatic brain metastasis. Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose for more than four weeks
* No allogeneic tissue/organ transplant
* Patients who will receive nivolumab in addition to chemotherapy must not have any contraindications to immune checkpoint inhibitors
* Patients must not have active autoimmune disease that has required systemic treatment within 6 months prior to registration. Patients are permitted to receive immunotherapy if they have vitiligo, type I diabetes, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
* Patients must not have a condition requiring systemic treatment with either corticosteroids (\>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses (=\< 10mg/day prednisone equivalent) are permitted
* Patients must not have a history of noninfectious pneumonitis requiring steroids
* Patients with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents are ineligible DRUG: Fluorouracil, DRUG: Leucovorin Calcium, DRUG: Oxaliplatin, DRUG: Irinotecan, BIOLOGICAL: Nivolumab, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Computed Tomography, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Advanced Esophageal Adenocarcinoma, Advanced Gastric Adenocarcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Esophageal Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Unresectable Esophageal Adenocarcinoma, Unresectable Gastric Adenocarcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma
Behavioral Exercise Training to Reduce Cardiovascular Disease Risk (EXTRA-PC)
Alexander R Lucas, PhD - Alexander.Lucas@vcuhealth.org
NCT06237179
Inclusion Criteria:
* Be diagnosed with stage II/III/IV prostate cancer
* Be currently undergoing treatment with ADT (intermittent or prolonged)
* Have completed local curative-intent treatment, including prostatectomy or definitive radiation;
* Be \>40 years of age up to 85;
* Be willing to sign an informed consent with HIPAA authorization form;
* Not have any hearing or sight impairments that result in the inability to use the telephone or hear normal conversation;
* Must be able to join an intervention group by personal computer, smartphone or telephone call and should agree to recording of an interview;
* Be without any serious medical condition that precludes safe participation in an exercise program;
* Speak English
Exclusion Criteria:
* Be unable to undergo MRI (i.e., ferromagnetic materials in body, inability to lie flat, claustrophobia);
* Have contraindications to exercise testing;
* Have pre-existing overt cardiovascular disease/heart failure;
* Active illness/infection;
* Hemoglobin \< 7.0 grams/dL
* Platelet count \< 10 x 109/L BEHAVIORAL: Exercise Training Intervention, BEHAVIORAL: Healthy Living Education
Prostate Cancer, Supportive Care
Prostate Cancer, Supportive Care, Exercise
Examining Lateralized Aspects of Motor Control Using Non-invasive Neural Stimulation
Brooke Dexheimer, PhD, OTD, OTR/L - dexheimerb@vcu.edu
NCT05947279
Inclusion Criteria:
* Right-handed as determined by the short-form Edinburgh Handedness Inventory
* Between the ages of 18 and 40
Exclusion Criteria:
* Mixed- or left-handed as determined by the short-form Edinburgh Handedness Inventory
* Self-reported history of any of the following:
Seizure and/or diagnosis of epilepsy Fainting spells Concussion with loss of consciousness Ringing in the ears (tinnitus) Cochlear implants Migraines Diagnosed psychological or neurological condition Metal in the scalp
* Any previous adverse reaction to a brain stimulation technique
* Any previous adverse reaction to 3D virtual reality environments (i.e. 'cybersickness')
* Possibility of being currently pregnant (for females only)
* Current open head wound or skin condition of the scalp
* Current implanted device(s) (i.e. cardiac pacemaker) BEHAVIORAL: Comparing motor adaptation reaching performance
Motor Adaptation and Generalization, Posterior Parietal Cortex, Cerebellum
Testing Continuous Versus Intermittent Treatment With the Study Drug Zanubrutinib for Older Patients With Previously Untreated Mantle Cell Lymphoma
Anne Beaven, MD - anne_beaven@med.unc.edu
NCT05976763
Inclusion Criteria:
* • Histologically confirmed mantle cell lymphoma with cyclin D1 (BCL1) expression by immunohistochemical stains and/or evidence of CCND1 rearrangement or t(11;14)(q13;q32) as confirmed by the enrolling center (such as by fluorescence in situ hybridization \[FISH\], polymerase chain reaction \[PCR\]/sequencing, karyotype). Patients with cyclin D1 and/or t(11;14) negative mantle cell lymphoma with an expression profile suggesting a diagnosis of mantle cell lymphoma \[MCL\] such as SOX11 expression are also eligible
* Any stage allowed (stage I-IV)
* Patient must have at least one objective measurable disease parameter by PET or CT. Measurable disease in the liver is required if the liver is the only site of lymphoma OR bone marrow involvement by MCL
* Steroids for management of mantle cell lymphoma are allowed up to a dose of prednisone 100mg/day (or equivalent) for up to 7 days prior to registration
* No prior systemic treatment for mantle cell lymphoma
* No prior radiation treatment for stage I MCL
* No prior exposure to a BTK inhibitor or anti-CD20 monoclonal antibody
* No prior stem cell transplant
* Age \>= 70 years OR age \>= 60 to \< 70 years with comorbidities precluding autologous stem cell transplantation (autoSCT) including at least one of the following: a) cardiac ejection fraction (EF) \<= 45%, b) diffusing capacity for carbon monoxide \<= 60% predicted; c) creatinine clearance \< 70 but \>= 30ml/minute (min); d) Eastern Cooperative Oncology Group (ECOG) performance status of 2, which poses an unacceptable risk of toxicity for high-dose therapy and stem cell transplantation; or e) Cumulative Illness Rating Scales (CIRS) total score \> 6
* ECOG Performance Status 0-2
* Absolute neutrophil count (ANC) \>= 750/mm\^3 (without growth factor support within 7 days)
* Platelet count \>= 75,000/mm\^3 (or \>= 50,000/mm\^3 if thrombocytopenia is due to lymphoma) without growth factor support or transfusion within 7 days
* Creatinine clearance \>= 30 mL/ min determined by either: a) Estimation using the Cockcroft-Gault equation or b) Measurement by nuclear medicine scan or 24 hour urine collection
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome)
* Aspartate transferase (AST) / alanine transaminase (ALT) =\< 3 x ULN
* Patients should not be considered candidates for stem cell transplant or must have declined a stem cell transplant strategy
* No clinically significant cardiovascular disease including the following
* Unstable angina within 3 months before registration
* New York Heart Association class III or IV congestive heart failure
* History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
* Known QT correction formula (QTcF) \> 480 msecs based on Fredericia's formula (unless pacemaker in place)
* History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* No active Hepatitis B or Hepatitis C infection. Patients with prior hepatitis B virus (HBV) exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of hepatitis C virus (HCV) 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
* No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
* No history of stroke or intracranial hemorrhage within 6 months prior to registration
* No disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Patient must be able to swallow pills
* Potential trial participants should have recovered from major surgery
* No vaccination with a live vaccine within 35 days prior to registration
* No hypersensitivity to zanubrutinib or rituximab or any of the other ingredients of the study drugs
* Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study.
* Patients on strong CYP3A4 inducers must discontinue the drug 14 days prior to registration. DRUG: Zanubrutinib, BIOLOGICAL: Rituximab, OTHER: Patient Observation, PROCEDURE: Bone Marrow Biopsy, OTHER: Fludeoxyglucose F-18, PROCEDURE: Positron Emission Tomography, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Esophagogastroduodenoscopy, PROCEDURE: Colonoscopy, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Mantle Cell Lymphoma
Health Education Approach to Lung Screening (HEALS)
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06070870
Inclusion Criteria:
* Meets current USPSTF guidelines for lung cancer screening (LCS)
* 20 pack-year smoking history Note: A pack-year is a way of calculating how much a person has smoked in their lifetime.
One pack-year is the equivalent of smoking an average of 20 cigarettes-1 pack-per day for a year.
* Currently smokes or has quit smoking within the past 15 years
* Identifies as Black or African-American Note: Both Hispanic/Latino and Non-Hispanic/Latino patients are eligible as long as they also identify as Black or African-American (eg, Afro-Latino).
* Willing to complete all navigation-related study activities
* Able to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
A patient who meets any of the following exclusion criteria is ineligible to participate in the study:
* Known history of cancer (except squamous cell skin cancer), or coughing up blood in the past 5 years, as reported by the individual
* Has undergone a previous lung cancer screening
* Inability to speak English
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements BEHAVIORAL: Patient Navigation
Lung Cancer
Lung cancer, Screening
Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality (REMAIN1)
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06370000
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed non-Acute Promyelocytic (APL) FLT3 negative AML and have completed induction and consolidation as defined by the treating physician and must be in complete response (CR), Complete response with partial hematologic recovery (CRh), or Complete response with incomplete count recovery (CRi) at time of study enrollment
* For patients in CR1, AML disease phenotype must be one that is considered for allo HCT in CR1 (intermediate or high risk by European Leukemia Net (ELN), MRD+ CR, slow clearance of MRD) or any AML phenotype (aside from FLT3+ and APL) in CR2 and beyond
* Medically eligible for allogeneic hematopoietic cell transplant (allo HCT) as defined by either: treating physician discretion, transplant physician discretion, or hematopoietic cell transplantation-specific Comorbidity index (HCT-CI) index of 5 or less
* Age ≥ 18 years
* Enrollment must occur within 4 months of completion of therapy
* A patient or staff identified health disparity in 1 of the 5 Centers for Disease Control (CDC) defined social determinants of health (SDOH). This may include financial difficulties, lack of caregiver support, difficulties with medical literacy, rurality, appropriate access to health care, lack of an appropriate allogeneic hematopoietic cell transplant (allo HCT) donor, substance abuse
* Patient must have adequate organ function defined as: Creatinine clearance (by Cockroft-Gault formula) greater than or equal to 29 mL/min, total bilirubin and aspartate aminotransferase/ alanine transaminase (AST/ALT) ≤ to institutional 2x upper limit of normal (except Gilbert's syndrome, which may enroll if \< 2x patient's baseline total bilirubin)
* Eastern Cooperative Oncology Group (ECOG) 0,1,2,3
* Ability to take oral medications
* No history of malabsorption syndrome which, in the investigator's opinion, may inhibit absorption of oral medications
* Women of childbearing potential must consent to effective contraception during study treatment and at least 6 months following the last dose. Women who are breastfeeding are also excluded
* Male patients must consent to effective contraception during study and at least 3 months after last dose
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria A patient who meets any of the following exclusion criteria is ineligible to participate in the study.
* FMS-like tyrosine kinase 3 (FLT3 ITD) or tyrosine kinase domain (TKD) mutation
* Uncontrolled central nervous system (CNS) involvement
* History of hypersensitivity or allergic reaction to azacitidine or its components
* Stem cell transplant within previous 3 months prior to initiation of study therapy
* Uncontrolled intercurrent illness or infection
* History of prior therapy with oral azacitidine
* Female patients who are pregnant or intend to donate eggs during the study or for 6 months after receiving their last dose of study drug
* Male patients who intend to donate sperm during the course of this study or for 3 months after last dose
* Other malignancy for which the patient is currently receiving therapy (except excisable skin cancer)
* 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: Oral Azacitidine
Acute Myeloid Leukemia
Targeted Treatment for Metastatic Prostate Cancer, The PREDICT Trial (PREDICT)
Rana McKay, MD - rmckay@health.ucsd.edu
NCT06632977
Inclusion Criteria:
* PRE-REGISTRATION: Histological or cytological evidence of prostate cancer. Patients with variant histologies including neuroendocrine, small cell and sarcomatoid prostate cancer are allowed to enroll and these will not be used as selection criteria for individual arms. Central pathology review is not required.
* PRE-REGISTRATION: Measurable disease and/or non-measurable metastatic disease per RECIST version 1.1.
* PRE-REGISTRATION: Tissue procured within 12 months of pre-registration (metastatic disease preferred over primary tissue, though both are acceptable) available for submission per Section 6.2. For patients who have progressed on A032102 and are pre-registering again, repeat tissue procurement will not be mandated.
* PRE-REGISTRATION: Molecular report available performed as part of standard of care testing via any Clinical Laboratory Improvement Act (CLIA)-certified next generation sequencing (NGS) assay. Patients may be assigned based on pre-determined qualifying molecular/DNA alterations as stated in Section 4.8 after receipt of local molecular testing by the A032102 molecular tumor board (MTB). Final determination of arm assignment will be determined by the MTB. For qualifying DNA alteration determined by the MTB, testing may be from tumor tissue collected at any time or circulating tumor DNA (ctDNA) within 12 months of pre-registration. If no qualifying DNA alteration is identified based on the CLIA-certified next generation sequencing assay and MTB review, Caris testing, should be performed for both DNA/RNA profiling. Arm assignment based RNA requires testing of tumor tissue collected within 12 months of pre-registration and MTB review.
* PRE-REGISTRATION: Age ≥ 18 years.
* REGISTRATION: Progressive mCRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND one or more of the following criteria (choose all the apply):
* PSA progression, defined by at least 2 consecutive rising PSA values at a minimum of 1-week intervals with the most recent PSA value being 2.0 ng/mL or higher, if confirmed PSA rise is the only indication of progression. Patients who received an anti-androgen must have PSA progression after withdrawal of anti-androgen therapy.
* Radiographic progression per RECIST 1.1 criteria for soft tissue lesions
* Bone metastasis progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
* REGISTRATION: Patients selected to receive lutetium Lu 177 vipivotide tetraxetan treatment are required to have prostate-specific membrane antigen (PSMA) positive mCRPC as determined by investigator assessment. For reference, in the VISION trial this was defined as at least 1 PSMA+ metastatic lesion (defined as uptake greater than that of liver parenchyma in lesions of any size in any organ system) and no PSMA- lesions (defined as uptake equal to or lower than that of liver parenchyma in any lymph node with a short axis of at least 2.5 cm, in any solid organ lesion with a short axis of at least 1.0 cm, or in any bone lesion with a soft-tissue component of at least 1.0 cm in the short axis).
* REGISTRATION: Prior treatment with androgen receptor signaling inhibitor (ARSI) in either the metastatic hormone sensitive setting or mCRPC is required. Prior taxane therapy in either metastatic hormone sensitive setting or mCRPC is mandated unless patient is taxane ineligible or the patient refuses taxane therapy. Prior lutetium LU177 vipivotide tetraxetan treatment is permitted but not mandated. Patients with known germline or somatic deleterious BRCA 1/2 mutations must have received a prior PARPi.
* REGISTRATION: Resolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic, stable grade 2 toxicities (defined as no worsening to \> grade 2 for at least 3 months prior to registration and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, comprised of:
* Chemotherapy-induced neuropathy
* Fatigue
* Residual toxicities from prior treatment: Grade 1 or grade 2 endocrinopathies which may include: Hypothyroidism/hyperthyroidism. type I diabetes, hyperglycemia, adrenal insufficiency, adrenalitis, skin hypopigmentation (vitiligo)
* REGISTRATION: No cytotoxic, biologic, radiopharmaceutical or other non-kinase inhibitor investigational agent within 4 weeks of registration. Treatment with any type of small molecular kinase inhibitor (including investigational kinase inhibitor) within 2 weeks of registration. Treatment with abiraterone acetate, apalutamide, or darolutamide within 2 weeks of registration. Treatment with enzalutamide within 4 weeks of registration. No treatment with radiation therapy within 2 weeks of registration.
* REGISTRATION: No major surgery within 4 weeks of registration.
* REGISTRATION: No prior treatment with EZH inhibitors.
* REGISTRATION: Prior treatment with cabazitaxel + carboplatin.
* REGISTRATION: None of the following conditions:
* Current use of moderate or strong cytochrome P450 (CYP)3A inducers.
* Known or suspected hypersensitivity to valemetostat tosylate (DS-3201b) or any of the excipients.
* 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.
\* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* Imminent or established spinal cord compression based on clinical and/or imaging findings.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to registration after radiotherapy or at least 4 weeks prior to registration after major surgery (e.g., removal or biopsy of brain metastasis). Patients must have complete wound healing from major surgery or minor surgery before registration.
* Significant cardiovascular defined as:
* Myocardial infarction within 6 months prior to enrollment.
* Uncontrolled angina pectoris within 6 months prior to enrollment.
* New York Heart Association Class 3 or 4 congestive heart failure.
* Corrected QT interval calculated by the Fridericia\'s formula (QTcF) ≥ 470 ms per electrocardiogram (ECG) within 42 days before randomization in any individual with any history of any cardiac disease or medication which can impact QTcF. Patients with known history or current symptoms of cardiac disease, history of treatment with cardiotoxic agents, or agents/conditions known to impact QTcF should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and ECG.
* Uncontrolled hypertension (resting systolic blood pressure \>160 mmHg or diastolic blood pressure \> 100 mmHg).
* Clinically significant acute infection requiring systemic antibacterial, antifungal or antiviral therapy.
* Moderate to severe hepatic impairment (Child-Pugh Class C)
* REGISTRATION: No freezing or donating sperm ≤ 14 days prior to registration.
* REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* REGISTRATION: No granulocyte colony-stimulating factor (GCSF) within 2 weeks of registration.
* REGISTRATION: No red blood cell (RBC) transfusions within 2 weeks of registration.
* REGISTRATION: No platelet transfusions within 2 weeks of registration.
* REGISTRATION: No bleeding diathesis.
* REGISTRATION: White blood cell count (WBC) ≥ 2,500/mcL.
* REGISTRATION: Absolute neutrophil count (ANC) ≥ 1,500/mcL.
* REGISTRATION: Hemoglobin ≥ 9 g/dL.
* REGISTRATION: Platelet count ≥ 100,000/mcL.
* REGISTRATION: Creatinine clearance ≥ 30 mL/min as defined by Cockcroft-Gault equation.
* REGISTRATION: Total bilirubin ≤ 1.5 x ULN (≤ 3 x upper limit of normal \[ULN\] for subjects with documented Gilbert\'s disease).
* REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
* REGISTRATION: Albumin ≥ 2.8 g/dL.
* REGISTRATION: The A032102 molecular tumor board will review the local pathology report and molecular sequencing report, and the Alliance registration/randomization office will relay the assignment to the submitting site. Once the site receives this assignment, they can register the patient to A032102. Any questions about the molecular board treatment assignments can be directed to A032102@alliancenctn.org.
* RE-REGISTRATION: Progressive mCRPC (after receiving the tumor board assigned therapy) as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND 2) progressive disease defined by radiographic progression on conventional imaging (CT/MRI chest, abdomen and pelvis and bone scan within 42 days of re-registration).
* RE-REGISTRATION: Resolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) resolved to CTCAE version 5.0, grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic, stable grade 2 toxicities (defined as no worsening to \> grade 2 for at least 3 months prior to registration and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, comprised of:
* Chemotherapy-induced neuropathy
* Fatigue
* Residual toxicities from prior treatment: Grade 1 or grade 2 endocrinopathies which may include: Hypothyroidism/hyperthyroidism. type I diabetes, hyperglycemia, adrenal insufficiency, adrenalitis, skin hypopigmentation (vitiligo).
* RE-REGISTRATION: None of the following conditions:
* Imminent or established spinal cord compression based on clinical and/or imaging findings.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to registration after radiotherapy or at least 4 weeks prior to re-registration after major surgery (e.g., removal or biopsy of brain metastasis). Patients must have complete wound healing from major surgery or minor surgery before re-registration.
* Corrected QT interval calculated by the Fridericia\'s formula (QTcF) \< 470 ms per ECG within 42 days before randomization in any individual with any history of any cardiac disease or medication which can impact QTcF.
* Significant cardiovascular defined as:
* Myocardial infarction within 6 months prior to enrollment.
* Uncontrolled angina pectoris within 6 months prior to enrollment.
* New York Heart Association Class 3 or 4 congestive heart failure.
* Uncontrolled hypertension (resting systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg).
* RE-REGISTRATION: ECOG Performance Status 0-2.
* RE-REGISTRATION: No GCSF within 2 weeks of registration.
* RE-REGISTRATION: No RBC transfusions within 2 weeks of registration.
* RE-REGISTRATION: No platelet transfusions within 2 weeks of registration.
* RE-REGISTRATION: WBC ≥ 2,500/mcL.
* RE-REGISTRATION: ANC ≥ 1,500/mcL.
* RE-REGISTRATION: Hemoglobin ≥ 9 g/dL (transfusions permitted).
* RE-REGISTRATION: Platelet count ≥ 100,000/mcL.
* RE-REGISTRATION: Creatinine clearance ≥ 30 mL/min as defined by Cockcroft-Gault equation.
* RE-REGISTRATION: Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert\'s disease).
* RE-REGISTRATION: AST and ALT ≤ 3 x ULN.
* RE-REGISTRATION: Albumin ≥ 2.8 g/dL.
* RE-REGISTRATION: QT Interval (QTcF) \< 470 ms (in individuals with any cardiac history of any medication or condition known to impact QTcF).
* RE-REGISTRATION: The A032102 molecular tumor board will review the CARIS molecular sequencing report, the Alliance registration/randomization office will relay the assignment to the site. Any questions about the molecular board treatment assignments can be directed to A032102@alliancenctn.org.
Exclusion Criteria:
\- OTHER: Genetic testing, DRUG: Valemetostat Tosylate, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Computed Tomography, PROCEDURE: Bone scan, PROCEDURE: FDG-Positron Emission Tomography, PROCEDURE: PSMA PET Scan, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cabazitaxel, DRUG: Abiraterone Acetate, DRUG: Enzalutamide, DRUG: Lutetium Lu 177 Vipivotide Tetraxetan
Castration-Resistant Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8
Comparison of EVAR and ESAR for Infrarenal Aortic Aneurysms With a Wide Proximal Neck (HERCULES)
Suzanne Holewijn, PhD - herculestrial@rijnstate.nl
NCT05484115
Inclusion Criteria:
* Age 18 years or older
* Provided written informed consent
* Clinical necessity for treatment of the AAA, according to the current guidelines in the geographies participating
* Elective repair
* Eligible anatomy for treatment with the Endurant II/IIs stent graft system and Heli-FX EndoAnchor system according to the IFU of both devices
* Infrarenal neck diameter ≥ 28 mm and ≤32 mm
* Proximal neck length ≥10mm
Exclusion Criteria:
* Anatomy outside the IFU of the ndurant II/IIs stent graft system and Heli-FX EndoAnchor system
* Planned use of AUI main body device
* Patient is participating in another clinical study, potentially conflicting with the outcomes of the current study.
* Patient with eGFR \< 30 ml/min/1.73m2 before the intervention
* Patient's life expectancy \<2 years as judged by the investigator
* Patient has a psychiatric or other condition that may interfere with the study
* Patient has a known allergy to any device component
* Patients with a systemic infection who may be at increased risk of endovascular graft infection.
* Patient has a coagulopathy or uncontrolled bleeding disorder
* Patient has a ruptured, leaking, or mycotic aneurysm
* Patient is not eligible for standard EVAR
* Patient had a Cerebro Vascular Accident (CVA) or a myocardial infarction (MI) within the prior three months
* Patient is pregnant (Female patients of childbearing potential only)
* Patient has active COVID-19 infection or has been diagnosed with long COVID-19 requiring hospitalization within the 6 months prior to procedure.
* Patient has previously been treated with stent grafts in the aorto-iliac arteries DEVICE: endovascular aneurysm repair (EVAR) using the Endurant II/IIs stent graft system, DEVICE: endosuture aneurysm repair (ESAR) using Heli-FX EndoAnchor system
Aortic Aneurysm, Abdominal
AAA, Endovascular treatment, Wide proximal neck, EndoAnchors, Infrarenal, EVAR (Endovascular aneurysm repair), ESAR (Endosuture aneurysm repair), Endurant II/IIs stent graft system, Heli-FX EndoAnchor system
GZ17-6.02 in Advanced CRPC After Progression on Anti-Androgen Therapy
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06636123
Inclusion Criteria:
* Patients diagnosed with prostate cancer and treated with androgen deprivation therapy (ADT) and at least one androgen receptor pathway inhibitor (ARPI) (eg, abiraterone, enzalutamide, apalutamide or darolutamide). Previous prostate-specific membrane antigen (PSMA)-targeted therapy or cytotoxic chemotherapy is allowed but not required.
* Androgen levels ≤50 ng/dL (≤1.73 nmol/L).
* Disease progression following ADT and ARPI treatment described
* PSA progression over 2 assessments, defined as rising PSA values from 2 consecutive assessments with an interval of at least 7 days between assessments. PSA levels prior to study enrollment are considered and appropriate for inclusion.
* Measurable disease by RECIST v1.1 on chest/abdomen/pelvis CT or evaluable disease observed on bone scan.
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Appropriate hepatic function defined by a total bilirubin (TBL) ≤1.5 × the upper limit of normal (ULN), alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) ≤3 × ULN at screening.
* Appropriate kidney function defined by calculated or actual creatinine clearance ≥30 mL/min
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3.
* Platelets ≥100,000 cells/mm3.
* Serum hemoglobin level ≥8 g/dL.
* Agree to not donate blood or sperm during the study and for 90 days after the last dose of study treatment.
* Patients with sexual partners of childbearing potential must agree to use highly effective methods of contraception throughout the study
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Any investigational agent:
within 4 weeks OR within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, before initiating study treatment.
* Low PSA (≤10 ng/mL) at initial presentation (before ADT or at symptomatic progression in the castrate setting) plus high volume (≥20) bone metastases.
* Simultaneous enrollment in any other cancer treatment interventional clinical trial.
* Active, uncontrolled diarrhea leading to dehydration or electrolyte disturbances not controlled with oral repletion.
* Grade ≥3 uncontrolled infection.
* Major surgery (in the opinion of the treating investigator) ≤3 weeks before initiating study treatment.
* Not having fully recovered to a grade of 1 or lower from any surgery-related adverse effects within the 3 weeks preceding the start of the study treatment.
* Small cell, anaplastic, or neuroendocrine component.
* Known active brain metastasis.
* Known active leptomeningeal disease.
* Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the medications included in the study treatment must be discontinued ≥2 weeks prior to initiating study treatment unless otherwise noted:
* Monoamine oxidase inhibitors (MAOI) use; must discontinue use 10 days prior to initiating study therapy.
* Strong or moderate CYP1A2, CYP3A4 and CYP2C19 inhibitors.
* Rucaparib, Olaparib and Talazoparib, due to their common findings of liver enzyme elevation.
* Inability to swallow medication.
* Known hypersensitivity to GZ17-6.02 components (curcumin, harmine, and isovanillin) or excipients.
* Known or suspected malabsorption condition or obstruction.
* Active untreated hepatitis B or C" and "Known liver cirrhosis of any cause, active nonalcoholic steatohepatitis, or nonalcoholic fatty liver disease. Note: no additional testing necessary to confirm
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements DRUG: Investigational Agent Administration
Castration-resistant Prostate Cancer
Study of ATX-01 in Participants With DM1 (ArthemiR)
Project Manager - clinical@arthexbiotech.com
NCT06300307
Key
Inclusion Criteria:
* Participants with a documented clinical diagnosis of DM1 (CTG expansion of \>150 repeats in DMPK gene measured in peripheral blood mononuclear cells)
* Ambulatory, defined as able to complete a 10-meter walk/run test at screening without the use of assistive devices such as canes, walkers, or orthoses, except for ankle-foot orthoses
* Presence for \>3 seconds of grip myotonia as confirmed by a central reader
Key Exclusion Criteria:
* Participants with congenital DM1
* Medical Research Council Muscle Scale score of less than 4 on ankle dorsiflexion or significant tibialis anterior atrophy that prevents a muscle biopsy
* Use of mexiletine or other agent for myotonia within 21 days or 5 half-lives, whichever is longer, prior to screening DRUG: ATX-01, DRUG: Placebo
Myotonic Dystrophy 1