StudyFinder
Search Results
631 Study Matches
Study to Evaluate Adverse Events and Change in Disease Activity With Oral Capsules of Galicaftor/Navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 Combination Therapies in Adult Participants With Cystic Fibrosis
ABBVIE CALL CENTER - abbvieclinicaltrials@abbvie.com
Phase 2
NCT04853368
Inclusion Criteria:
• Confirmed clinical diagnosis of cystic fibrosis (CF).
• Arm 1 participants with genotype homozygous for the F508del CF transmembrane conductance regulator (CFTR) mutation and not receiving elexacaftor/tezacaftor/ivacaftor (ETI) treatment .
• Arm 2 and 3 participants with genotype heterozygous for the F508del CFTR mutation and a minimal function and not receiving ETI treatment.
• Arm 4 participants with genotype either homozygous or heterozygous for the F508del mutation. Participants must be receiving stable (ETI) treatment.
• Percent predicted forced expiratory volume in 1 second (ppFEV1) >= 40% and <=90% of predicted normal for age, gender and height at screening.
• For arms 1 and 2: sweat chloride (SwCl) >= 60 mmol/L at screening. For participants who participated in Study M19-530, it is acceptable to use a SwCl value that the central lab provided in Study M19-530 to establish eligibility.
• Weight >= 35 kg at screening and Day -28 for arm 1 or day 1 for arms 2 to 4.
Exclusion Criteria:
• Clinically significant laboratory values at screening that would pose undue risk for the participant or interfere with safety assessments (per the investigator).
Drug: ABBV-576, Drug: Galicaftor, Drug: Placebo, Drug: Navocaftor, Drug: ABBV-119
Cystic Fibrosis (CF)
Cystic Fibrosis (CF), Galicaftor, Navocaftor, ABBV-119, ABBV-576
Improving Exercise Capacity With a Tailored Physical Activity Intervention (PALS)
Study Coordinator - kristin.johnson@advocatehealth.org
NA
NCT05595577
Inclusion Criteria:
To be considered eligible, participants must meet all of the following criteria:
* Individuals aged 18- 85 years
* Diagnosed with stage I-IV Hodgkin's or non-Hodgkin's lymphoma or stage I-III breast cancer
* Expected to receive an anthracycline based chemotherapeutic regimen or other potentially cardiotoxic cancer therapies (e.g. chemotherapy regimens \[anthracyclines, trastuzumab, rituximab\]), immuno-therapies (immune checkpoint inhibitors \[ICI's\]) or radiation (within 8 weeks of completion of radiation).29-31
* Ability to speak and understand English
* Capacity to walk at least 2 city blocks (\~.2 miles) on a flat surface
* Expected survival beyond 6 months.
* Must have an assistant that will help perform the home-based testing activities
Exclusion Criteria:
If the patient meets any of these criteria they are excluded from the study:
* Uncontrolled hypertension (systolic blood pressure \>190 mm Hg or diastolic blood pressure \>100 mm Hg)
* Recent history of alcohol or drug abuse, inflammatory conditions such as lupus or inflammatory bowel disease, or another medical condition that might compromise safety or successful completion (unless approved by the participant's physician and the Principal Investigator) NOTE: In the setting of active inflammation, participation will not be approved. If chronic disease is present and stable as judged by the participant's physician and the PI, participation will be approved.
* Contraindications to MRI such as ferromagnetic cerebral aneurysm clips or other intracranial metal, pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices (unless approved by the participant's physician and the Principal Investigator)
* Pregnant
* Unstable angina
* Contraindication for exercise training or testing
* Inability to exercise on a treadmill or stationary cycle
* Significant ventricular arrhythmias (\>20 PVCs/min due to gating difficulty)
* Atrial fibrillation with uncontrolled ventricular response
* Acute myocardial infarction within 28 days
* Inability to provide informed consent OTHER: Exercise with Trainerize application, DIAGNOSTIC_TEST: Cardiopulmonary exercise testing, DIAGNOSTIC_TEST: MRI scan, BEHAVIORAL: Quality of Life Questionnaires, BEHAVIORAL: Cognitive and Brain Function Questionnaires, OTHER: Blood draws
Non Hodgkin Lymphoma, Heart, Functional Disturbance, Hodgkin Lymphoma, Quality of Life, Stage I Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer
Exercise capability, Brain activity
Impact of 4PCP on Practitioner and Patient Outcomes (4PCP)
Thomas Chelimsky, M.D. - thomas.chelimsky@vcuhealth.org
NA
NCT05580419
Practitioner Inclusion:
* General practitioners
* Part of a practice that has their own identifiable patient population including patients with chronic pain
* Able to fully answer questionnaires
* Able to attend 4PCP course
* English speaking
Patient inclusion:
* Age 14-80
* Self-report of chronic non-malignant pain \> 3 months
* No foreseeable or planned surgeries for chronic pain
* Has attended at least 2 established visits in the enrolled practitioner's practice
* English speaking
Practitioner exclusion:
* Pain specialists
* Unable to fully answer questionnaires
* Unable to attend the 4PCP course
* Non-English speaking
Patient exclusion:
* Unable to answer questionnaires (e.g. stroke, dementia, developmental delay, etc.)
* Followed in a specialty pain clinic (PCP not managing pain care)
* Sickle cell disease
* Prisoners
* Non-English speaking
BEHAVIORAL: 4PCP Course
Chronic Pain
FearLess in Cognitively Intact Patients With Glioma (FearLess)
Ashlee Loughan, PhD - ashlee.loughan@vcuhealth.org
N/A
NCT05604365
Inclusion Criteria:
Patient inclusion:
• Confirmed glioma diagnosis (grade II-IV) via histopathology
• Be a minimum of 2 weeks post surgical repair or biopsy (if applicable)
• Elevated FCR [> 13 on Fear of Cancer Recurrence Inventory]
• Primarily English speaking Caregiver Inclusion:
• Loved one, or non-paid care partner to a patient with a confirmed glioma diagnosis (grade II-IV) via histopathology
• Elevated FCR [> 13 on Fear of Cancer Recurrence Inventory]
• Primarily English speaking
• Age 18+
Exclusion Criteria:
Patient:
• Cognitive impairment [< or equal to 31 on the Telephone Interview for Cognitive Status (TICS)]
• Inability to attend virtual sessions (e.g. due to lack of stable internet connection, difficulty using technology)
• Inability to understand and provide informed consent. Caregiver:
• Inability to attend virtual sessions (e.g. due to lack of stable internet connection, difficulty using technology)
• Inability to understand and provide informed consent.
Behavioral: FearLess Intervention
Glioma, Fear of Cancer
Salad Bars in the National School Lunch Program: Impact on Dietary Consumption Patterns in Elementary School Students
Sarah M Farthing, MS - sarah.malone@vcuhealth.org
NCT05605483
Inclusion Criteria:
Students
• All K-6th grade students at target schools who participate in the school lunch program on
rating day
Cafeteria staff
• All cafeteria personnel at the randomly selected target schools will be eligible to
complete surveys
Exclusion Criteria:
Students
• Unsure sex of child
Cafeteria staff
• None
Other: Salad bar, Other: Waitlisted control
Diet, Food, and Nutrition
Study of Tecovirimat for Human Monkeypox Virus (STOMP)
ACTG Clinicaltrials.gov Coordinator - ACTGCT.gov@fstrf.org
Phase 3
NCT05534984
Inclusion Criteria (All participants; Arms A, B, and C):
• Laboratory-confirmed or presumptive HMPXV infection.
• HMPXV illness of <14 days duration immediately prior to study entry.
• At least one active (not yet scabbed) skin lesion, mouth lesion, or proctitis with or without visible ulcers.
• Non-pregnant people of reproductive potential must agree to use at least one effective means of contraception when engaging in sexual activities that can result in pregnancy, from the time of enrollment through the end of study participation. Additional Inclusion Criteria for Arms A and B:
• Age ≥18 years at the time of study entry Additional Inclusion Criteria for Arm C; Participants who meet the above entry criteria who also meet any of the following criteria will be registered to Arm C:
• Participants age <18 years at the time of study entry
• Those with severe HMPXV disease Those with or without severe disease and with one or more of the following will also be enrolled into Arm C:
• Severe immunosuppression
• Skin conditions placing the person at higher risk for disseminated infection Exclusion Criteria (All participants; Arms A, B, and C):
• Prior or concomitant receipt of tecovirimat (e.g., under an alternative access mechanism.
• Planned initiation of intramuscular cabotegravir/rilpivirine during study drug administration or for two weeks following completion of study drug administration. Participants who are stable on long-acting intramuscular cabotegravir/rilpivirine may enroll.
• Participants who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study.
• Participants who require intravenous dosing of tecovirimat.
• Laboratory-confirmed or presumptive HMPXV infection.
• HMPXV illness of <14 days duration immediately prior to study entry.
• At least one active (not yet scabbed) skin lesion, mouth lesion, or proctitis with or without visible ulcers.
• Non-pregnant people of reproductive potential must agree to use at least one effective means of contraception when engaging in sexual activities that can result in pregnancy, from the time of enrollment through the end of study participation. Additional Inclusion Criteria for Arms A and B:
• Age ≥18 years at the time of study entry Additional Inclusion Criteria for Arm C; Participants who meet the above entry criteria who also meet any of the following criteria will be registered to Arm C:
• Participants age <18 years at the time of study entry
• Those with severe HMPXV disease Those with or without severe disease and with one or more of the following will also be enrolled into Arm C:
• Severe immunosuppression
• Skin conditions placing the person at higher risk for disseminated infection Exclusion Criteria (All participants; Arms A, B, and C):
• Prior or concomitant receipt of tecovirimat (e.g., under an alternative access mechanism.
• Planned initiation of intramuscular cabotegravir/rilpivirine during study drug administration or for two weeks following completion of study drug administration. Participants who are stable on long-acting intramuscular cabotegravir/rilpivirine may enroll.
• Participants who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study.
• Participants who require intravenous dosing of tecovirimat.
Drug: Tecovirimat Oral Capsule, Drug: Placebo, Drug: Tecovirimat Oral Capsule (Open Label)
Monkeypox
HMPXV
Study of Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant (Prevent)
Dee Rodriguez - ClinicalTrials@allovir.com
Phase 2/Phase 3
NCT05305040
Key
• ≥1 year of age at the day of screening visit.
• No known or suspected clinically significant disease from AdV, BKV, CMV, EBV, HHV-6, and/or JCV
• Within 15 and 42 days of receiving a first allogeneic HCT and have demonstrated clinical engraftment
• Meet one or more of the following criteria at the time of randomization:
• Related (sibling) donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B or -DR
• Haploidentical donor
• Matched or Mismatched unrelated donor
• Use of umbilical cord blood as stem cell source
• Ex vivo graft manipulation resulting in T cell depletion
• Received anti-thymocyte globulin or alemtuzumab (Campath-1H) Key
• History of AdV, BKV, CMV, EBV, HHV-6, and/or JCV end-organ disease within 6 months prior to randomization
• Evidence of active Grade >2 acute GVHD
• Presence of non-minor uncontrolled or progressive bacterial, viral or fungal infections
• Known history or current (suspected) diagnosis of CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose >0.5 mg/kg/day) within 24 hours prior to dosing
• Relapse of primary malignancy other than minimal residual disease Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria:
• ≥1 year of age at the day of screening visit.
• No known or suspected clinically significant disease from AdV, BKV, CMV, EBV, HHV-6, and/or JCV
• Within 15 and 42 days of receiving a first allogeneic HCT and have demonstrated clinical engraftment
• Meet one or more of the following criteria at the time of randomization:
• Related (sibling) donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B or -DR
• Haploidentical donor
• Matched or Mismatched unrelated donor
• Use of umbilical cord blood as stem cell source
• Ex vivo graft manipulation resulting in T cell depletion
• Received anti-thymocyte globulin or alemtuzumab (Campath-1H) Key
Exclusion Criteria:
• History of AdV, BKV, CMV, EBV, HHV-6, and/or JCV end-organ disease within 6 months prior to randomization
• Evidence of active Grade >2 acute GVHD
• Presence of non-minor uncontrolled or progressive bacterial, viral or fungal infections
• Known history or current (suspected) diagnosis of CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose >0.5 mg/kg/day) within 24 hours prior to dosing
• Relapse of primary malignancy other than minimal residual disease Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Biological: Posoleucel (ALVR105), Biological: Placebo
Adenovirus Infection, BK Virus Infection, Cytomegalovirus Infections, Epstein-Barr Virus Infections, Human Herpes Virus-6 Infection, JC Virus Infection
Allogeneic Hematopoietic Cell Transplant, ALVR105, Posoleucel, Viralym-M
A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark)
Study Contact - Participate-In-This-Study@its.jnj.com
Phase 1/Phase 2
NCT05488314
Inclusion Criteria:
• Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) non-small cell lung cancer (NSCLC) (any histology)
• May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for greater than (>) 2 weeks and who are off or receiving low-dose corticosteroid treatment (less than or equal to [<=]10 milligrams (mg) prednisone or equivalent) for at least 2 weeks prior to start of study treatment
• May have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
Exclusion Criteria:
• Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets
• Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms
• Participant has uncontrolled tumor-related pain: Symptomatic lesions amenable to palliative radiotherapy (example, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the administration of the first study treatment
Drug: Capmatinib, Drug: Amivantamab
Carcinoma, Non-Small-Cell Lung
Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1) (VIKTORIA-1)
Nadene Zack, MS - VIKTORIA-1_TRIAL@CELCUITY.COM
PHASE3
NCT05501886
Inclusion Criteria:
• Histologically or cytologically confirmed diagnosis of metastatic or locally advanced breast cancer Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue on it for the duration of the study.
• Negative pregnancy test for women of childbearing potential. Female subjects of childbearing potential must use an effective and/or acceptable contraceptive method from screening until 1 year after the last dose of study treatment
• Confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive, as per American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines (2020), based on most recent tumor biopsy utilizing an assay consistent with local standards
• Documented HER2 immunohistochemistry (IHC) negative as per ASCO-CAP 2018 guidance
• Adequate archival or fresh tumor tissue for the analysis of PIK3CA mutational status
• Subject must have documentation of radiological disease progression on or after the last prior treatment and also have radiologically evaluable disease (measurable and/or non-measurable) according to RECIST v1.1, per local assessment. Subjects with bone only disease must have lytic or mixed lytic/blastic lesions that can be accurately assessed; bone only blastic lesions with no soft tissue component is not allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy of at least 3 months
• Progressed during or after CDK4/6 inhibitor combination treatment with non-steroidal aromatase inhibitor (AI)
• Adequate bone marrow, hepatic, renal and coagulation function
Exclusion Criteria:
• History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥3 years
• Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
• Prior treatment with chemotherapy and antibody drug conjugates for advanced disease is not permitted (prior adjuvant or neoadjuvant chemotherapy is permitted)
• More than 2 lines of prior endocrine therapy treatment
• Bone only disease that is only blastic with no soft tissue component
• Subjects with type 1 diabetes or uncontrolled type 2 diabetes
• Known and untreated, or active, brain or leptomeningeal metastases a. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they meet the following criteria: do not require supportive therapy with steroids; do not have seizures and do not exhibit uncontrolled neurological symptoms; stable disease confirmed by radiographic assessment within at least 4 weeks prior to enrollment
• Patients with advanced, symptomatic, visceral spread that are at risk of life-threatening complication in the short-term
• History of clinically significant cardiovascular abnormalities such as: Congestive heart failure (New York Heart Association (NYHA) classification ≥ II within 6 months of study entry
• Myocardial infarction within 12 months of study entry
• History of any uncontrolled (or untreated) 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), supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months
• Uncontrolled hypertension defined by systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without antihypertensive medication (initiation or adjustment of antihypertensive medication\[s\] is allowed prior to screening)
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: * i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, or history of clinically significant/symptomatic bradycardia * ii. On screening, inability to determine the corrected QT interval using Fridericia's formula (QTcF) on the ECG (i.e., unreadable or not interpretable) or QTcF \>480 msec (determined by mean of triplicate ECGs at screening)
• Known hypersensitivity to the study drugs or their components
• Pregnant or breast-feeding women
• Concurrent participation in another interventional clinical trial
• Subjects must agree not to participate in another clinical trial (other than observational) at any time during participation in VIKTORIA-1.
DRUG: Gedatolisib, DRUG: Palbociclib, DRUG: Fulvestrant, DRUG: Alpelisib
Breast Cancer
Breast Cancer, Advanced or Metastatic, gedatolisib, HR Positive, ER Positive, HER2 Negative, PIK3CA MT, PI3K
LGMD R1 Natural History Study (GRASP-01-003)
Ruby Langeslay - ruby.langeslay@vcuhealth.org
NCT05618080
Inclusion Criteria:
• Age between 12-50 at enrollment
• Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with LGMDR1)
• Genetic confirmation of LGMDR1 (presence of homozygous or compound heterozygous pathogenic mutations in CAPN3).
• Must be able to provide written informed consent and be willing and able to comply with all study requirements. Note: Adult participants must be able to provide consent themselves. Legally authorized representatives are not permitted to consent on behalf of adult participants.
Exclusion Criteria:
• Have contraindications to MRI or MRS (e.g., non-MR compatible implanted medical devices or severe claustrophobia)
• Non-ambulatory as defined by those who are not able to walk 10 meters without assistive devices (ankle foot orthotics excluded)
• Positive pregnancy test at any timepoint during the trial
• Have dominantly inherited CAPN3 mutations (LGMDD4)
• Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator.
Calpain-3 Deficiency Limb Girdle Muscular Dystrophy Type 2A, Limb Girdle Muscular Dystrophy, Limb Girdle Muscular Dystrophy Type R1, LGMD2A
LGMD, Limb Girdle Muscular Dystrophy, LGMD R1, LGMD2A, CAPN3
Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Natural History With Its Numerous Co-morbidities?
Gisela Chelimsky, M.D. - gisela.chelimsky@vcuhealth.org
NA
NCT05618054
Inclusion Criteria:
* Females 12-21 years old
* Able to communicate and provide consent/assent
* English speaking
* Diagnosed with POTS (POTS will be defined standardly as a symptomatic ≥ 40 bpm rise in heart rate without a drop in blood pressure and with symptoms of orthostatic intolerance clinically)
* Age-matched healthy control subjects: no POTS or other neurological disorders
Exclusion Criteria:
* Inflammatory arthritis, connective tissue or auto-immune disorder
* Any chronic neurological disorder besides POTS
* Evidence of unstable medical disorder, such as kidney (rising creatinine, or end-stage renal failure) or liver impairment (rising AST or ALT, or end-stage with coagulopathy), poorly controlled significant cardiovascular (CHF), respiratory, endocrine (diabetes - A1c \> 9 - or untreated thyroid dysfunction) or uncontrolled psychiatric illness (such as untreated depression, psychosis, etc.)
* Neuropathy, central nervous system disorder (e.g., Cerebral palsy, developmental delay, seizure disorder, MS, stroke, etc.)
* Treatment with a drug or medical device within the previous 30 days that has not received regulatory approval
* Use of hormones (except insulin, thyroid replacement or oral contraceptives, which will be carefully documented)
* Current substance or alcohol abuse
* Any major surgical intervention with general anesthesia in the last 60 days and minor procedure, such as tooth extraction, endoscopy, etc., with local or conscious sedation within 7 days
* Any on-going or pending medical, health or disability related litigation, or current pursuit of disability
* Any condition that in the judgment of the investigator would interfere with the patient's ability to provide informed consent, comply with study instructions, place the patient at increased risk, or which would clearly confound the interpretation of the study results (specific reason will be documented)
* Chronic use of narcotics for pain
* Claustrophobia or any metal hardware that may interfere with MRI
* Investigators and study staff BEHAVIORAL: Looming task
Postural Tachycardia Syndrome
Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score, The Guidance Trial
ctrrecruit@vcu.edu
PHASE3
NCT05050084
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate within 270 days prior to registration
* Unfavorable intermediate risk prostate cancer, defined as having ALL the following bulleted criteria:
* Has at least one intermediate risk factor (IRF):
* PSA 10-20 ng/mL
* Clinical stage T2b-c (digital rectal examination \[DRE\] and/or imaging) by American Joint Committee on Cancer (AJCC) 8th edition
* Gleason score 7 (Gleason 3+4 or 4+3 \[ International Society of Urological Pathology (ISUP) Grade Group 2-3\])
* Has ONE or more of the following 'unfavorable' intermediate-risk designators:
* \> 1 immature reticulocyte fraction (IRF)
* Gleason 4+3=7 (ISUP Grade Group 3)
* \>= 50% of biopsy cores positive
* Biopsies may include 'sextant' sampling of right/left regions of the prostate, often labeled base, mid-gland and apex. All such 'sextant' biopsy cores should be counted. Men may also undergo 'targeted' sampling of prostate lesions (guided by MRI, ultrasound or other approaches). A targeted lesion that is biopsied more than once and demonstrates cancer (regardless of number of targeted cores involved) should count as a single additional positive core sampled and positive. In cases of uncertainty, count the biopsy sampling as sextant core(s)
* Absence of high-risk features
* Appropriate stage for study entry based on the following diagnostic workup:
* History/physical examination within 120 days prior to registration;
* Negative bone imaging (M0) within 120 days prior to registration; Note: Tc-99m bone scan or sodium fluoride (NaF) positron emission tomography (PET) are allowed. Equivocal bone scan findings are allowed if plain films X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) are negative for metastasis at the concerned site(s). While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for bone imaging, any suspicious findings must be confirmed and correlated with conventional imaging (Tc-99m bone scan, NaF PET, CT, X-ray, or MRI) to determine eligibility based on the latter modalities (e.g. M0 based on conventional imaging modalities)
* Clinically negative lymph nodes (N0) as established by conventional imaging (pelvic +/- abdominal CT or MR), within 120 days prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are =\< 1.0 cm in short axis and/or if biopsy is negative.
Note: While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA) PET may be counted as acceptable substitute for pelvic imaging, any suspicious findings must be confirmed by conventional imaging (CT, MRI or biopsy). If the findings do not meet pathological criteria based on the latter modalities (e.g. node =\< 10 mm in short axis, negative biopsy), the patient will still be eligible
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
* Non-castrate testosterone level (\> 50 ng/dL) within 120 days prior to registration
* Absolute neutrophil \>= 1,000 cells/mm\^3 (within 120 days prior to registration)
* Hemoglobin \>= 8.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
* Platelet count \>= 100,000 cells/mm\^3 independent of transfusion and/or growth factors (within 120 days prior to registration)
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)
* For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR \>= 30 mL/min/1.73m\^2 will be considered adequate
* Total bilirubin: 1.5 =\< institutional upper limit of normal (ULN) (within 120 days prior to registration) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is less than or equal to 1.5 x ULN, subject is eligible)
* Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]): =\< 2.5 x institutional ULN (within 120 days prior to registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial; Note: HIV testing is not required for eligibility for this protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
* For patients with a 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
* Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
* Previous radical surgery (prostatectomy) or any form of curative-intent ablation whether focal or whole-gland (e.g., cryosurgery, high intensity focused ultrasound \[HIFU\], laser thermal ablation, etc.) for prostate cancer
* Definitive clinical or radiologic evidence of metastatic disease (M1)
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. History of or current diagnosis of hematologic malignancy is not allowed
* Prior radiotherapy to the prostate/pelvis region that would result in overlap of radiation therapy fields
* Previous bilateral orchiectomy
* Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate). ADT started prior to study registration is not allowed
* Prior use of 5-alpha-reductase inhibitors is allowed, however, it must be stopped prior to enrollment on the study with at least a 30 day washout period before baseline study PSA measure and registration
* Active testosterone replacement therapy; any replacement therapy must be stopped at least 30 days prior to registration
* Severe, active co-morbidity defined as follows:
* Current severe or unstable angina;
* New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
* History of any condition that in the opinion of the investigator, would preclude participation in this study
* Inability to swallow oral pills
* High risk features, which includes any of the following:
* Gleason 8-10 \[ISUP Grade Group 4-5\]
* PSA \> 20
* cT3-4 by digital exam OR gross extra-prostatic extension on imaging \[indeterminate MRI evidence will not count and the patient will be eligible\] DRUG: Bicalutamide, DRUG: Buserelin, DRUG: Darolutamide, DRUG: Degarelix, DRUG: Flutamide, DRUG: Goserelin, DRUG: Histrelin, DRUG: Leuprolide, RADIATION: Radiation Therapy, DRUG: Relugolix, DRUG: Triptorelin
Prostate Adenocarcinoma
Upifitamab Rilsodotin Maintenance in Platinum-Sensitive Recurrent Ovarian Cancer (UP-NEXT) (UP-NEXT)
Rita Lemming - medicalinformation@mersana.com
Phase 3
NCT05329545
Inclusion Criteria:
• Participant must have a histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube and primary peritoneal cancer, that is metastatic or recurrent.
• Participant must have platinum-sensitive recurrent disease, defined as having achieved either a partial or complete response to 4 or more cycles in their penultimate platinum- containing regimen and their disease progressing more than 6 months after completion of the last dose of platinum containing therapy in the penultimate regimen.
• Participant must have had 4 to 8 cycles of platinum-based chemotherapy in 2nd to 4th line setting in their most recent treatment regimen as defined below:
• Platinum-based chemotherapy regimens allowed immediately preceding enrollment to the study: carboplatin or cisplatin ±: paclitaxel, docetaxel, pegylated liposomal doxorubicin or gemcitabine.
• Participant must receive first study treatment infusion between 4 and 12 weeks after completing final dose of platinum in the most recent platinum-based regimen.
• Participant must have had as their best response to last line of treatment one of the following: No Evidence of Disease (NED); Complete Response (CR); Partial Response (PR); OR Stable Disease (SD)
• Participants with NED, CR, or PR as their best response to most recent line of treatment and who have not received treatment with a prior PARP inhibitor must have definitive BRCA1 and BRCA2 testing results that demonstrate no evidence of a deleterious BRCA1 or BRCA2 mutation. Somatic BRCA mutation testing is required for participants who are classified as not having a deleterious mutation by germline testing alone.
• Participant must provide either a tumor tissue block or fresh cut slides for measurement of NaPi2b expression by a central laboratory. If sufficient archival tumor tissue is not available, then a tumor tissue block or slides must be obtained from a fresh biopsy and provided to the central laboratory. Confirmation of a NaPi2b-H/positive tumor by the central laboratory is required prior to randomization.
Exclusion Criteria:
• Participant has received prior treatment with mirvetuximab soravtansine or another ADC containing an auristatin or maytansinoid payload.
• Participant has received bevacizumab in combination with last platinum-based regiment or plans to receive maintenance therapy outside the study intervention.
• Participant has clinical signs or symptoms of gastrointestinal obstruction and/or requirement for parenteral hydration or nutrition.
• Participant has ascites or pleural effusion managed with therapeutic paracentesis or thoracentesis within 28 days prior to signing the principal study consent form.
• Participant has history of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease. Testing beyond laboratory studies otherwise defined in the eligibility criteria, to diagnose potentially clinically significant liver disease based on risk factors such as hepatic steatosis or history of excessive alcohol intake, will be based on clinical judgement of the investigator.
• Participant has history of or suspected pneumonitis or interstitial lung disease.
• Participant has untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis, or carcinomatous meningitis.
Drug: Upifitimab rilsodotin, Other: Placebo
High Grade Serous Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer
Ovarian Cancer, Serous, Maintenance, Antibody Drug Conjugate, Recurrent, Platinum-Sensitive, ADC, Fallopian Tube Cancer, Primary Peritoneal Cancer
Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer
ctrrecruit@vcu.edu
PHASE1
NCT05172245
Inclusion Criteria:
* Patients must have pathologically confirmed HNSCC (including tumors of the oropharynx, hypopharynx, larynx, oral cavity, nasal cavity, maxillary and other paranasal sinuses, and unknown primary of the head and neck), with measurable disease as per RECIST 1.1
* Oropharyngeal and unknown primary squamous cell cancers must test for human papilloma virus (HPV), for example by p16 immunohistochemistry (IHC), in situ hybridization (ISH), or polymerase chain reaction (PCR). HPV testing is not required for other HNSCC primary tumor sites
* For the dose escalation phase only (not the expansion phase), patients with p16-positive tumors are eligible if clinical stage III (cT4 or cN3, M0) according to the American Joint Committee on Cancer (AJCC)/TNM Staging System, 8th edition (Ed.)
* For both the dose escalation and expansion phases, patients with p16-negative (or not tested) tumors are eligible if clinical stage III-IVB (locally advanced but non-metastatic) according to the AJCC/TNM Staging System, 8th Ed.
* Must be candidate for concurrent, definitive cisplatin and radiation therapy as judged by the treating physician
* Able to swallow tablets at the time of enrollment
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of ipatasertib in combination with chemoradiation in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Life expectancy of greater than 3 months
* Absolute neutrophil count \>= 3000/mcL
* Hemoglobin \>= 10 g/dL
* Platelets \>= 150,000/mcL
* Serum albumin \>= 3 g/dL
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN / 2 x institutional ULN
* Alkaline phosphatase (ALP) =\< 2.0 x institutional ULN
* Partial thromboplastin time (PTT) (or activated \[a\]PTT) and international normalized ratio (INR) =\< 1.5 institutional ULN (except for patients receiving anticoagulation therapy)
* Creatinine clearance (CLcr) \> 60 mL/min
* For this calculation, use the Cockroft-Gault formula
* Fasting glucose =\< 150 mg/dL (8.3 mmol/L) and (when indicated) glycosylated hemoglobin (HbA1c ) =\< 7.5% (58 mmol/mol)
* Human immunodeficiency virus (HIV)-infected patients are eligible if on effective anti-retroviral therapy with undetectable viral load within 6 months
* Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative hepatitis B virus surface antigen \[HBsAg\] test and a positive hepatitis B core antibody \[HBcAb\] test, accompanied by a negative HBV deoxyribonucleic acid \[DNA\] test) are eligible. Patients with chronic HBV infection are eligible if the HBV viral load is undetectable on suppressive therapy, if indicated. Patients undergoing current treatment with anti-viral therapy for HBV are ineligible
* Patients with a history of hepatitis C virus (HCV) infection are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). Patients with HCV infection who are currently on treatment 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
* The effects of ipatasertib on the developing human fetus are unknown. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 28 days after the last dose of ipatasertib and agreement to refrain from donating eggs during this same period. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 28 days after the last dose of ipatasertib
* Ability to understand and the willingness to sign a written informed consent document
* For the expansion cohort only, patients must agree to undergo mandatory on-treatment biopsies, and have tumors amenable to on-treatment biopsies. This is not applicable to the dose escalation cohort where no on-treatment biopsies are obtained
Exclusion Criteria:
* Primary tumor of nasopharynx, salivary, thyroid or parathyroid glands, or skin
* Distant metastases from the current HNSCC
* Prior treatment (e.g., chemotherapy, radiation, or definitive surgery) for the current locally advanced HNSCC is not permitted. Biopsies, including those performed under anesthesia, are not considered surgery. Patients who underwent prior definitive surgery alone for an early stage (T1-2N0) HNSCC which has now recurred with stage III-IVB disease at least 3 months after the initial surgery are eligible
* For patients with a prior history of another malignancy, no prior chemotherapy or radiation may have been administered within 6 weeks prior to study entry. Among patients who received prior radiation to the head and neck or adjacent anatomical site for another malignancy, there may be no overlap with current area to be irradiated
* Current use of any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib or other agents used in study
* Treatment with strong inhibitors or inducers of CYP3A4 or P-glycoprotein within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Patients with uncontrolled intercurrent illness, including active infection
* Pregnant women are excluded from this study because ipatasertib is an oral AKT inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ipatasertib, breastfeeding should be discontinued if the mother is treated with ipatasertib. These potential risks may also apply to other agents used in this study
* Patients with type I or type II diabetes mellitus requiring insulin at study entry. Patients with non-insulin dependent type II diabetes mellitus are eligible, as are patients who are on a stable dose of oral diabetes medication \>= 4 weeks prior to initiation of study treatment. Patients with a history of diabetes mellitus, an abnormal fasting glucose level, or other signs or symptoms indicating diabetes mellitus, must meet the laboratory eligibility criteria for fasting blood glucose and hemoglobin A1c
* History of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
* History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
* Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
* Known clinically significant history of liver disease consistent with Child Pugh Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B surface antigen \[HBsAg\] or hepatitis C virus \[HCV\] antibody at screening), or cirrhosis
* Grade \>= 2 uncontrolled or untreated hypercholesterolemia (cholesterol \> 300 mg/dL or \> 7.75 mmol/L) or hypertriglyceridemia (triglycerides \> 300 mg/dL or \> 3.42 mmol/L) PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Ipatasertib, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy
Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Head and Neck Carcinoma of Unknown Primary, Locally Advanced Head and Neck Squamous Cell Carcinoma, Locally Advanced Hypopharyngeal Squamous Cell Carcinoma, Locally Advanced Laryngeal Squamous Cell Carcinoma, Locally Advanced Nasal Cavity Squamous Cell Carcinoma, Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Advanced Oropharyngeal Squamous Cell Carcinoma, Locally Advanced Paranasal Sinus Squamous Cell Carcinoma, Locally Advanced Sinonasal Squamous Cell Carcinoma, Maxillary Sinus Squamous Cell Carcinoma, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage III Sinonasal Cancer AJCC v8, Stage IVA Hypopharyngeal Carcinoma AJCC v8, Stage IVA Laryngeal Cancer AJCC v8, Stage IVA Lip and Oral Cavity Cancer AJCC v8, Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVA Sinonasal Cancer AJCC v8, Stage IVB Hypopharyngeal Carcinoma AJCC v8, Stage IVB Laryngeal Cancer AJCC v8, Stage IVB Lip and Oral Cavity Cancer AJCC v8, Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVB Sinonasal Cancer AJCC v8
Conditioning SCID Infants Diagnosed Early (CSIDE)
Allison Neutzling - aweiss@nmdp.org
PHASE2
NCT03619551
Inclusion Criteria:
1\. Infants with SCID, either typical or leaky or Omenn syndrome.
• Typical SCID is defined as either of the following * Absence or very low number of T cells (CD3+ T cells \<300/microliter AND no or very low T cell function (\<10% of lower limit of normal) as measured by response to phytohemagglutinin OR * Presence of maternally derived T cells
• Leaky SCID is defined as the following • Absence of maternally derived T cells • AND either one or both of the following (i, ii): i) \<50% of lower limit of normal T cell function as measured by response to PHA OR \<30% of lower limit of normal T cell function as measured by response to CD3 ii) Absent or \<10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (must document post vaccination or exposure for this criterion to apply) • AND at least two of the following (i through iii): i) CD3 T cells \< 1500/microliter ii) \>80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR \>80% of CD3+ or CD4+ T cells are CD62L negative AND/OR \>50% of CD3+ or CD4+ T cells express HLA-DR (at \< 4 years of age) AND/OR are oligoclonal T iii) Low TRECs and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower level of normal.
• Omenn syndrome • Generalized skin rash * Maternal lymphocytes tested for and not detected. * \>80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR \>80% of CD3+ or CD4+ T cells are CD62L negative AND/OR \>50% of CD3+ or CD4+ T cells express HLA-DR (\<2 years of age) * Absent or low (up to 30% lower limit of normal (LLN)) T cell proliferation to antigens (Candida, tetanus) to which the patient has been exposed IF: Proliferation to antigen was not performed, but at least 4 of the following 8 supportive criteria, at least one of which must be among those marked with an asterisk (\*) below are present, the patient is eligible as Omenn Syndrome.
• Hepatomegaly
• Splenomegaly
• Lymphadenopathy
• Elevated IgE
• Elevated absolute eosinophil count
• \*Oligoclonal T cells measured by CDR3 length or flow cytometry (upload report)
• \*Proliferation to PHA is reduced to \< 50% of lower limit of normal (LLN) or SI \< 30
• \*Low TRECs and/or percentage of CD4+/RA+ CD31+ or CD4+/RA+ CD62L+ cells below the lower level of normal 2\. Documented mutation in one of the following SCID-related genes a. Cytokine receptor defects (IL2RG, JAK3) b. T cell receptor rearrangement defects (RAG1, RAG2) 3. No available genotypically matched related donor (sibling) 4. Availability of a suitable donor and graft source
• Haploidentical related mobilized peripheral blood cells
• 9/10 or 10/10 allele matched (HLA-A, -B, -C, -DRB1, -DQB1) volunteer unrelated donor mobilized peripheral blood cells 5. Age 0 to 2 years at enrollment Note: to ensure appropriate hepatic metabolism, age at time of busulfan start: For IL2RG/JAK3: 8 weeks For RAG1/RAG2: 12 weeks 6\. Adequate organ function defined as:
• Cardiac: Left ventricular ejection fraction (LVEF) at rest ≥ 40% or, shortening fraction (SF) ≥ 26% by echocardiogram.
• Hepatic: Total bilirubin \< 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and AST and ALT \< 5.0 x ULN for age.
• Renal: GFR estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is \< 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 50 mL/min/1.73 m2.
• Pulmonary No need for supplemental oxygen and O2 saturation \> 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care).
Exclusion Criteria:
• Presence of any serious life-threatening or opportunistic infection at time of enrollment and prior to the initiation of the preparative regimen. Serious infections as defined below that occur after enrollment must be reported immediately to the Study Coordinating Center, and enrollment will be put on hold until the infection resolves. Ideally enrolled subjects will not have had any infection. If patients have experienced infections, these must have resolved by the following definitions: a. Bacterial i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat culture(s) from same site must be negative and patient has completed appropriate course of antibacterial therapy (typically at least 10 days). ii. Tissue-based clinical infection (e.g. cellulitis): Complete resolution of clinical signs (e.g. erythema, tenderness, etc.) and patient has completed appropriate course of antibacterial therapy (typically at least 10 days). iii. Pneumonia, organism not identified by bronchoalveolar lavage: Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed appropriate course of antibacterial therapy (typically at least 10 days). If possible, radiographic resolution should also be demonstrated. b. Fungal i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat culture(s) from same site is negative and patient has completed appropriate course of antifungal therapy (typically at least 14 days). The patient may be continued on antifungal prophylaxis following completion of the treatment course. c. Pneumocystis i. Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed appropriate course of therapy (typically at least 21 days). If possible, radiographic resolution should also be demonstrated. The patient may be continued on prophylaxis following completion of the treatment course. d. Viral i. Viral PCRs from previously documented sites (blood, nasopharynx, CSF) must be re-tested and are negative. ii. If re-sampling a site is not clinically feasible (i.e. BAL fluid): Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.). If possible, radiographic resolution should also be demonstrated.
• Patients with HIV or HTLV I/II infection will be excluded.
DRUG: Busulfan, DEVICE: Cell processing for TCRαβ+/CD19+ depletion
SCID
Improving Transition Care for Adolescents and Young Adults With Type 1 Diabetes (SHIFT2)
Sarah Farthing - sarah.malone@vcuhealth.org
NA
NCT05639088
Inclusion Criteria:
AYA:
• Type 1 Diabetes diagnosis for at least 1 year (as documented in medical record)
• 16-22 years old
• English speaking
• Children's Hospital of Richmond patient (Division of Pediatric Endocrinology)
• must have a caregiver willing to participate Caregiver:
• Age greater than 18 years
• Provides care to AYA and willing to participate
Exclusion Criteria:
AYA:
• Non-English speaking
• Significant psychiatric, cognitive, medical or developmental conditions that would impair their ability to complete assessments and/or engage in diabetes self-care behaviors (e.g., malignancies, psychosis, intellectual disability
• Hospitalization for depression, suicidal ideation or other psychiatric disorder within the past 12 months. Life time history of psychotic disorder
• Medically-induced diabetes or diagnosis of diabetes other than type 1 diabetes.
• Currently pregnant, pregnant within the past 6 months, currently breastfeeding or planning to become pregnant within the next 12 months.
• Another member of the household (other than the participating parent) is a participant or staff member on this study.
• Participation in another research study that may interfere with this study.
• Previous participation in the SHIFT pilot study Caregiver:
• Non-English speaking
• Significant psychiatric, cognitive, developmental conditions that would impair their ability to complete assessments and/or engage in supporting the AYA with diabetes self-care behaviors (e.g., psychosis, intellectual disability)
• Another member of the home (not AYA) is a participant/staff member on current study
• Participation in another research study that may interfere with current study
• Previous participation in SHIFT pilot study
BEHAVIORAL: Transition preparation program, OTHER: Educational materials
Type 1 Diabetes
Diabetes Management, Transition
Prophylaxis With Direct-acting Antivirals for Kidney Transplantation From HCV-Infected Donors to Uninfected Recipients (PREVENT-HCV)
Christine Durand, MD - cdurand2@jhmi.edu
NA
NCT05653232
Inclusion Criteria:
* Participant meets the standard criteria for KT at local center.
* Participant is able to understand and provide informed consent.
* Participant is ≥ 18 years old.
Exclusion Criteria:
* Participant has active HCV infection (detectable HCV RNA) at time of screening.
* Participant has cirrhosis or advanced liver fibrosis.
* Participant's aspartate aminotransferase (AST) or ALT \> 2.5 times the upper limit of normal (ULN), within 60 days of screen.
* Participant has human immunodeficiency virus infection (HIV), or active hepatitis B (HBV) infection.
* Participant is unable to safely substitute or discontinue a medication that is contraindicated with the study medication.
* Past or current medical problems, which may pose additional risks from participation in the study, interfere with the participant's ability to comply with study, or impact the quality of the data obtained from the study.
* Participant is pregnant or breastfeeding. OTHER: Prophylaxis (P2W), OTHER: Transmit and Treat (T&T)
HCV
A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
ctrrecruit@vcu.edu
PHASE2
NCT04684368
Inclusion Criteria:
* Patients must be \>= 3 years and \< 30 years at the time of study enrollment
* Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or \> 10 ng/mL or human chorionic gonadotropin (hCG) beta \> 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 31 days prior to enrollment and start of protocol therapy \[repeat if necessary\]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy \[repeat if necessary\]). Basal ganglia or other primary sites are excluded
* Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols)
* Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 31 days prior to study enrollment and start of protocol therapy )
* Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior to study enrollment and start of protocol therapy)
* Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery
* Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age: Maximum serum creatinine (mg/dL)
* 3 to \< 6 years: 0.8 (male), 0.8 (female)
* 6 to \< 10 years: 1 (male), 1 (female)
* 10 to \< 13 years: 1.2 (male), 1.2 (female)
* 13 to \< 16 years: 1.5 (male), 1.4 (female)
* \>= 16 years: male (1.7), 1.4 (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
* Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.
* 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
* NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
* English-, Spanish-, or French- speaking
* Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive and quality of life assessments
* No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with NF1 will be allowed to participate
* Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery
* Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires
Exclusion Criteria:
* Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
* Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis
* Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids
* Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination)
* Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs
* Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Etoposide, BIOLOGICAL: Filgrastim, DRUG: Ifosfamide, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mesna, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Peripheral Blood Stem Cell Transplantation, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy, RADIATION: Radiation Therapy, PROCEDURE: Second-Look Surgery, DRUG: Thiotepa
Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor, Pineal Region Germ Cell Tumor, Pineal Region Immature Teratoma, Pineal Region Yolk Sac Tumor, Suprasellar Germ Cell Tumor
The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study
ctrrecruit@vcu.edu
PHASE1
NCT04726241
Inclusion Criteria:
* Patients must be less than 22 years of age at the time of study enrollment
* Patient must have one of the following at the time of study enrollment:
* Patient has known or suspected relapsed/refractory (including primary refractory) AML as defined in protocol
* This includes isolated myeloid sarcoma
* Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome (ML-DS)
* Patient has known or suspected relapsed ALL as defined in protocol that meets one of the following criteria:
* Second or greater B-ALL medullary relapse, excluding KMT2Ar
* Any first or greater B-ALL medullary relapse involving KMT2Ar
* Any first or greater T-ALL medullary relapse with or without KMT2Ar
* Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia (MPAL) as defined in protocol
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML)
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS) or treatment-related myelodysplastic syndrome (t-MDS)
* Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)
* Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* 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
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Juvenile Myelomonocytic Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome Post Cytotoxic Therapy, Myeloid Leukemia Associated With Down Syndrome
Anticoagulation in ICH Survivors for Stroke Prevention and Recovery (ASPIRE)
Kevin N Sheth, MD - kevin.sheth@yale.edu
PHASE3
NCT03907046
Inclusion Criteria:
* Age at least 18 years
* Intracerebral hemorrhage (ICH) (including primary intraventricular hemorrhage) confirmed by brain CT or MRI
* Can be randomized within 14-180 days after ICH onset
* Non-valvular AF (defined as atrial fibrillation or atrial flutter), documented by electrocardiography or a physician-confirmed history of prior AF
* Provision of signed and dated informed consent form by patient or legally authorized representative
* For females of reproductive potential: use of highly effective contraception
Exclusion Criteria:
* Index event is hemorrhagic transformation of a brain infarction or hemorrhage into a tumor
* History of earlier ICH within 12 months preceding index event
* Active infective endocarditis
* Clear indication for anticoagulant drugs (e.g., requires anticoagulation for deep vein thrombosis or pulmonary embolism) or antiplatelet drugs (e.g., requires aspirin or clopidogrel for recent coronary stent).
* Previous or planned left atrial appendage closure
* Clinically significant bleeding diathesis
* Serum creatinine ≥2.5 mg/dL
* Active hepatitis or hepatic insufficiency with Child-Pugh score B or C
* Anemia (hemoglobin \<8 g/dL) or thrombocytopenia (\<100 x 10\^9/L) that is chronic in the judgment of the investigator
* Pregnant or breastfeeding
* Known allergy to aspirin or apixaban
* Concomitant participation in a competing trial
* Considered by the investigator to have a condition that precludes safe or active participation in the trial
* Persistent, uncontrolled systolic blood pressure (≥180 mm Hg)
* ICH caused by an arteriovenous malformation (AVM) that has not yet been secured DRUG: Apixaban, DRUG: Aspirin
Intracerebral Hemorrhage, Atrial Fibrillation
A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer (ROCC)
Jennifer Klein, MEd - jklein@gog.org
NA
NCT04831580
Inclusion Criteria:
• Patient must have histologically confirmed adenocarcinoma (usual/classic/NOS), squamous cell carcinoma, adenosquamous carcinoma (Including glassy cell)
• Patient must be FIGO Stage IA2, IBI, IB2 (2018 staging) without evidence of definitive parametrial, vaginal, nodal or distant metastases on exam or imaging. Patients with tumor size less than or equal to 4 cm confirmed on MRI prior to randomization are eligible.
• Patient must have uterine size \<12 cm AND felt to be appropriate for vaginal delivery of the specimen per investigator.
• Patient must be suitable surgical candidate with preoperative assessments such as labs and EKG performed per institutional standard and agree to be randomized to undergo open or robotic radical (or simple) hysterectomy. NOTE: Simple hysterectomy will be allowed in patients who meet the following criteria:
• pelvic MRI must demonstrate a maximal tumor size of 2 cm or less AND
• less than 50% stromal invasion on MRI if tumor present or less than 10 mm of stromal invasion if an excisional (cold knife or LEEP) has been performed. Submission of source documents in the GOG Partners Source Document Portal will be required prior to randomization for review and confirmation of simple hysterectomy being met (see Section 6.0 for instructions).
• Patient must be age 18 years or older.
• Patient must have ECOG performance status 0-1.
• Patient must have a negative urine pregnancy test within 30 days of surgery in pre-menopausal women.
• Patient must have signed an approved informed consent and authorization permitting the release of personal health information.
Exclusion Criteria:
• Patients with any tumor histology other than those listed above, specifically excluding the following histologies: neuroendocrine, other adenocarcinoma (gastric type, endometrioid, clear cell, serous, signet ring, minimal deviation)
• Patients with FIGO stage 1A1, IB3, II-IV (2018 staging).
• Patient with inability to receive an MRI.
• Patients with a tumor size greater than 4cm or on MRI confirmed prior to randomization are excluded. Patients with definite evidence of vaginal/parametrial involvement on MRI are excluded; if MRI findings are not definitive, then clinical examination must also not reveal parametrial or vaginal extension).
• Patients with evidence of metastatic disease (imaging or histologically positive lymph nodes).
• Patients with a history of prior pelvic or abdominal radiotherapy.
• Patients with a prior malignancy \< 5 years from enrollment with the exception of non-melanoma skin cancer.
• Patients who are unable to withstand prolonged lithotomy or steep trendelenberg.
• Patient compliance and geographic proximity that do not allow adequate follow-up.
• Patients with poorly controlled HIV with CD4 counts \<500.
DEVICE: da Vinci, OTHER: open surgery
Cervical Cancer
A Study of Nivolumab-relatlimab Fixed-dose Combination Versus Regorafenib or TAS-102 in Participants With Later-lines of Metastatic Colorectal Cancer (RELATIVITY-123)
BMS Study Connect Contact Center www.BMSStudyConnect.com - Clinical.Trials@bms.com
Phase 3
NCT05328908
Inclusion Criteria:
• Histological confirmed previously treated colorectal cancer with adenocarcinoma histology with metastatic or recurrent unresectable disease at study entry
• Participants must have:
• progressed during or within approximately 3 months following the last administration of approved standard therapies (at least 1, but not more than 4 prior lines of therapies), which must include a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF therapy, and anti-EGFR therapy (if KRAS wild-type), if available in the respective country, or;
• been intolerant to prior systemic chemotherapy regimens if there is documented evidence of clinically significant intolerance despite adequate supportive measures
• Must have sufficient tumor tissue & evaluable PD-L1 expression to meet the study requirements
• Must have measurable disease per RECIST v1.1. Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately
Exclusion Criteria:
• Prior treatment with either an immunotherapy or with regorafenib or with TAS-102
• Untreated central nervous system (CNS) metastases, participants are eligible if CNS metastases have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment)
• History of refractory hypertension not controlled with anti-hypertensive therapy, myocarditis (regardless of etiology), uncontrolled arrhythmias, acute coronary syndrome within 6 months prior to dosing, Class II congestive heart failure (as per the New York Heart Association Functional Classification), interstitial lung disease/pneumonitis or an active, known or suspected autoimmune disease
• Confirmed tumor microsatellite instable high/deficient mismatch repair (MSI-H/dMMR) status as per local standard testing; MSI/MMR test results from initial diagnosis are acceptable. Other protocol-defined inclusion/exclusion criteria apply
Drug: Nivolumab-relatlimab FDC, Drug: Regorafenib, Drug: TAS-102
Colorectal Neoplasms
Micro-satellite Stable (MSS) Metastatic Colorectal Cancer (mCRC), Relatlimab, Nivolumab, BMS-986213, Regorafenib, Stivarga, Lonsurf
A Study of BMS-986406 as Monotherapy and Combination Therapies in Participants With Advanced Tumors
BMS Study Connect Contact Center www.BMSStudyConnect.com - Clinical.Trials@bms.com
Phase 1
NCT05298592
Inclusion Criteria:
• Histologically or cytologically confirmed locally advanced unresectable, metastatic, or recurrent malignant tumor. Eligible tumor types are non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), pancreatic ductal adenocarcinoma (PDAC), gastric/gastroesophageal junction, castration-resistant prostate cancer (CRPC), ovarian, squamous cell carcinoma of the head and neck (SCCHN), bladder, melanoma, mesothelioma, triple negative breast cancer (TNBC), and soft tissue sarcoma, except for participants with tumors with central nervous system (CNS) metastases as the only site of active disease
• Measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), Prostate Cancer Working Group 3 (PCWG3) (for prostate cancer), or modified Response Evaluation Criteria in Solid tumors (mRECIST) (for mesothelioma)
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Adequate organ function
Exclusion Criteria:
• Prior organ or tissue allograft
• Leptomeningeal metastases
• Untreated CNS metastases
• Serious or uncontrolled medical disorders Other protocol-defined inclusion/exclusion criteria apply
Biological: BMS-986406, Biological: Nivolumab
Advanced Cancer
Opdivo®, Immunotherapy
Predicting Outcomes in Nonalcoholic Steatohepatitis With Advanced Fibrosis
Mohammad S Siddiqui, MD - mohammad.siddiqui@vcuhealth.org
NCT05720663
Inclusion Criteria:
Adult patients with presence of NAFLD associated cirrhosis.
* Cirrhosis: biopsy confirmed or Agile F (F4) score \> 0.45
* NAFLD as an etiology of liver disease will be determined based on presence of any of the following:
* Biopsy showing \>5% steatosis or
* CAP \> 280 dB/m or MR-PDFF\>5%
* If CAP \< 280 dB/m or MR-PDFF \<5%, then must have type 2 diabetes and or 2 or more features of metabolic syndrome for 5 years (cryptogenic cirrhosis)
Exclusion Criteria:
* Refusal to consent
* Alcohol use \> 14/21 gm/week cutoff
* Other causes of chronic liver disease
* MELD \> 12
* Hepatic and extrahepatic cancers expected to limit life expectancy \< 2 yrs
* prior hepatic resections, TIPS, splenic embolization
* prior decompensation events
* inability to fit into MRI (failed hula-hoop test)
* general contraindication for MRI contrast (GFR \< 30 ml/min)
* contraindications for MRI
* pregnancy
* acute kidney injury
* reduced kidney function (GFR \<30ml/min) OTHER: Standard of care
Nonalcoholic Steatohepatitis
Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma
ctrrecruit@vcu.edu
PHASE3
NCT05095376
Inclusion Criteria:
* STEP 1 REGISTRATION: No known IDH mutation. (If tested before step 1 registration, patients known to have IDH mutation in the tumor on local or other testing are ineligible and should not be registered)
* STEP 1 REGISTRATION: Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block and hematoxylin and eosin (H\&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Note that tissue for central pathology review and central MGMT assessment must be received by the New York University (NYU) Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 30. If tissue cannot be received by postoperative calendar day 30, then patients may NOT enroll on this trial as central pathology review will not be complete in time for the patient to start treatment no later than 8 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be completed within 10 business days of receipt of tissue. Results will be entered by the central lab directly into Rave. Note: In the event of an additional tumor resection(s), tissue must be received within 30 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection. Surgical resection is required; stereotactic biopsy alone is not allowed because it will not provide sufficient tissue for MGMT analysis
* STEP 1 REGISTRATION: Willing to use highly effective method of contraception for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 6 months after completing treatment; this inclusion is necessary because the treatment in this study may be significantly teratogenic
* STEP 1 REGISTRATION: The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
* STEP 2 REGISTRATION: Histopathologically proven diagnosis of glioblastoma (or gliosarcoma as a subtype of glioblastoma) confirmed by central pathology review
* STEP 2 REGISTRATION: MGMT promoter with methylation confirmed by central pathology review. Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or unmethylated MGMT promoter are excluded
* Note: Any MGMT result other than methylated would require step 2 registration to be reported as a "central review failure"
* STEP 2 REGISTRATION: Contrast-enhanced brain MRI performed either after surgery or prior to step 2 registration
* STEP 2 REGISTRATION: IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e IDH wildtype). (If a mutation is identified then the patient will be ineligible and must be registered as ineligible at step 2.)
* STEP 2 REGISTRATION: History/physical examination within 28 days prior to step 2 registration
* STEP 2 REGISTRATION: Karnofsky performance status (KPS) \>= 70 within 28 days prior to step 2 registration
* STEP 2 REGISTRATION: Neurologic function assessment within 28 days prior to step 2 registration
* STEP 2 REGISTRATION: Age 18-70 years
* STEP 2 REGISTRATION: Hemoglobin \>= 10 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 10.0 g/dl is acceptable) (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Leukocytes \>= 2,000/mm\^3 (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Absolute neutrophil count \>= 1,500/mm\^3 (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Platelets \>= 100,000/mm\^3 (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Total bilirubin =\< 1.5 x institutional/lab upper limit of normal (ULN) (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 2.5 x ULN (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: Serum creatinine =\< 1.5 x ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula) (Within 14 days prior to step 2 registration)
* STEP 2 REGISTRATION: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
* STEP 2 REGISTRATION: For 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
* Note: Known positive test for hepatitis C virus ribonucleic acid (HCV ribonucleic acid \[RNA\]) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
* STEP 2 REGISTRATION: Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to step 2 registration are eligible for this trial. Testing is not required for entry into protocol
* STEP 2 REGISTRATION: Negative serum or urine pregnancy test (in persons of childbearing potential) within 14 days prior to step 2 registration
* Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
Exclusion Criteria:
* STEP 2 REGISTRATION: Prior therapy for tumor except for resection or prior laser interstitial thermal therapy (LITT). For example, prior chemotherapy, immunotherapy, or targeted therapy for GBM or lower grade glioma is disallowed (including but not limited to temozolomide, lomustine, bevacizumab, any viral therapy, ipilimumab or other CTLA-4 antibody, PD-1 antibody, CD-137 agonist, CD40 antibody, PDL-1 or 2 antibody, vaccine therapy, polio or similar viral injection as treatment for the tumor, and/or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) as is Gliadel wafer, radiotherapy, radiosurgery, vaccine or other immunotherapy, brachytherapy, or convection enhanced delivery
* Note: 5-aminolevulinic acid (ALA)-mediated fluorescent guided resection (FGR) photodynamic therapy (PDT) or fluorescein administered prior to/during surgery to aid resection is not exclusionary and is not considered a chemotherapy or intracerebral agent. Prior laser interstitial thermal therapy (LITT) is allowed
* STEP 2 REGISTRATION: Current or planned treatment with any other investigational agents for the study cancer
* STEP 2 REGISTRATION: Definitive clinical or radiologic evidence of metastatic disease outside the brain
* STEP 2 REGISTRATION: Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ and melanoma in situ) unless disease free for a minimum of 2 years
* STEP 2 REGISTRATION: Prior radiotherapy to the head or neck that would result in overlap of radiation therapy fields
* STEP 2 REGISTRATION: Pregnancy and individuals unwilling to discontinue nursing due to the potential teratogenic effects and potential risk for adverse events in nursing infants
* STEP 2 REGISTRATION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or lomustine
* STEP 2 REGISTRATION: History of pulmonary fibrosis
* STEP 2 REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
* Ongoing or active infection requiring intravenous (IV) antibiotics, IV antiviral, or IV antifungal treatment
* Symptomatic congestive heart failure, defined as New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
* Unstable angina pectoris within 6 months prior to Step 2 registration
* Uncontrolled cardiac arrhythmia
* Psychiatric illness/social situations that would limit compliance with study requirements
* STEP 2 REGISTRATION: No evidence of diffuse leptomeningeal disease that requires whole brain irradiation DRUG: Lomustine, PROCEDURE: Magnetic Resonance Imaging, RADIATION: Photon Beam Radiation Therapy, OTHER: Questionnaire Administration, DRUG: Temozolomide
Glioblastoma, Gliosarcoma
Effectiveness of IVR Combined With Task-Specific Training on Hemiplegic Arm Function Following Stroke
Rahsaan Holley - holleyrj@vcu.edu
NA
NCT05728866
Inclusion Criteria:
* Age 18 or older.
* Diagnosed as having an ischemic or hemorrhagic stroke (with documented confirmatory neuroimaging in the medical record) that occurred at least 6-months prior to study enrollment.
* Lack of full active range of motion in the involved shoulder, elbow, and wrist as the result of the injury.
* At the time of study enrollment, participant completed structured therapeutic interventions at least 2-months prior.
* Participants will not participate in Yoga, Tai-Chi, or other wellness lifestyle classes while participating in the study.
* Absence of significant cognitive impairment as determined by a Mini-Mental Status Examination score of greater than or equal to 24.
* The absence of upper extremity injury limiting functional use of the arm prior to the incident stroke.
Exclusion Criteria:
* Unable to provide informed consent.
* Sensory loss as determined by a score of 2 on the sensory item of the NIH Stroke Scale.
* Pain in the involved upper limb that could interfere with daily activities as evidenced by a pain score of 5 or greater on the Numeric Pain Rating Scale.
* History of greater than two strokes.
* Suffered a stroke less than 6-months prior to participating in the study.
* A history of, or being susceptible to, cyber-sickness (i.e., motion sickness).
* Unable to don/doff accelerometer independently, or the lack of support in the home to assist with donning/doffing device; and
* A history of seizures. PROCEDURE: VR immersive therapy
Stroke
Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects With MDS or AML
Shattuck Clinical Trials - clinicaltrials@shattucklabs.com
Phase 1
NCT05275439
Inclusion Criteria:
• Subject has voluntarily agreed to participate by giving written informed consent in accordance with International Council for Harmonisation/Good Clinical Practice (ICH/GCP) guidelines and applicable local regulations.
• Age ≥ 18 years.
• For subjects with AML, confirmation of AML diagnosis by 2016 World Health Organization (WHO) criteria [Arber, 2016] classification, excluding acute promyelocytic leukemia (APL).
• Subjects with MDS must have:
• morphologically confirmed diagnosis of MDS by 2016 WHO criteria [Arber, 2016] with <20% blasts in bone marrow per bone marrow biopsy/aspirate or peripheral blood.
• confirmation of intermediate, high or very high risk category by Revised International Prognostic Scoring System (IPSS-R)
• Subjects with AML must have relapsed/refractory disease (>5% blasts by manual aspirate differential, flow cytometry, or immunohistochemistry) following at least 1 prior line of therapy but no more than 4 prior lines of therapy.
• Subjects with relapsed/refractory disease (as defined in Inclusion criterion 5) following at least 1 prior line of therapy but no more than 4 prior lines of therapy for AML or MDS.
• Subjects diagnosed with MDS must be previously untreated. Prior MDS therapy with lenalidomide or supportive care in the form of transfusions or growth factors is allowed.
• All subjects must have documentation of at least one tumor protein 53 (TP53) gene mutation/deletion based on local test.
• Subjects with previously untreated de novo AML or secondary AML with TP53 gene mutation or deletion and who are unlikely to benefit from standard intensive induction therapy or refuse intensive induction therapy at time of enrollment are eligible. All subjects must have documentation of at least one TP53 gene mutation/deletion based on local test. Subjects with secondary AML after MDS must not have received prior chemotherapy or no more than 2 cycles of prior hypomethylating agent for MDS.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2
• Laboratory values must meet the criteria outlined in the protocol.
• Willing to provide consent for bone marrow aspirate samples for exploratory research at baseline and on-treatment per schedule described in the Schedule of Assessments.
• For subjects with relapsed/refractory disease, recovery from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of the first dose of study treatment.
• Male subjects with female partners of childbearing potential must have azoospermia from a prior vasectomy or underlying medical condition or agree to use an acceptable method of contraception during treatment and for 30 days (which exceeds 5 half-lives) or for the duration required by local regulatory guidance, whichever is longer, after last dose of study treatment.
Exclusion Criteria:
• Subject with relapsed or refractory disease has received treatment for AML or MDS with any of the following:
• Chimeric antigen receptor (CAR)-T cell therapy
• Prior treatment with anti-cluster of differentiation 47 (CD47) targeting agent or cluster of differentiation 40 (CD40) agonist within 28 days prior to
• the first dose of study treatment.
• Prior treatment with signal-regulatory protein alpha (SIRPα)-targeting antibody
• Other experimental therapies for AML or MDS within 14 days or at least 5 half- lives (whichever is shorter) prior to the first dose of study treatment
• Evidence of active central nervous system (CNS) involvement with leukemia
• Subjects requiring agents other than hydroxyurea to control blast counts within 14 days prior to the first dose of study treatment.
• Evidence of active bleeding or bleeding diathesis or major coagulopathy (including familial)
• [Only for Cohorts including Venetoclax in the regimen] Subject has received strong and/or moderate cytochrome P450, family 3, subfamily A (CYP3A) inducers within 7 days prior to the first dose of study treatment.
• Use of corticosteroids or other immunosuppressive medication, current or within 14 days of the first dose of study treatment
• Receipt of live attenuated vaccine within 30 days of first dose of SL-172154 treatment, the exception is that vaccines for coronavirus disease 19 (COVID-19) are permitted.
• Subject has active, uncontrolled infection (e.g, viral, bacterial, or fungal). Subjects are eligible if infection is controlled with antibiotics, antivirals and/or antifungals.
• [Only for Cohorts including Venetoclax in the regimen] Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
• Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal disease associated with diarrhea within 6 months of first dose of study treatment.
• Clinically significant or uncontrolled cardiac disease including any of the following:
• Myocarditis
• Unstable angina within 6 months from D1 of study treatment
• Acute myocardial infarction within 6 months from D1 of study treatment
• Uncontrolled hypertension
• New York Heart Association (NYHA) Class III or IV congestive heart failure
• Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, second- or third- degree atrioventricular (AV) block without a pacemaker, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia not stabilized on therapy)
• Subject has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participation in the study.
• Subjects who have had any major surgical procedure within 14 days of first dose of study treatment.
• Subject is a woman who is pregnant or breast feeding or planning to become pregnant or breast feed while enrolled in this study.
• Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of adverse events (AEs) or compromised ability to provide written informed consent.
• Presence of another malignancy that requires active therapy and that in the opinion of the investigator and Sponsor would interfere with the monitoring of disease assessments in this study.
• Known hypersensitivity to any of the study medications including excipients of Azacitidine.
• Has undergone solid organ transplantation.
• Known or active human immunodeficiency virus (HIV) infection
• Known or active infection with hepatitis B (positive for hepatitis B surface antigen [HBsAg]) or hepatitis C virus ([HCV]; if hepatitis C virus (HCV) antibody (Ab) test is positive check for HCV ribonucleic acid [RNA]).
Drug: SL-172154
Acute Myeloid Leukemia, Myelodysplastic Syndromes
Oesophageal Protection Study: A Multicentre Study. (IMPACT II)
Patrick Shanley, MS - pshanley@attune-medical.com
N/A
NCT04577859
Inclusion Criteria:
• All AF patients deemed suitable for AF ablation treatment (under general anaesthetic) as
per international guidelines and the patient has already decided on AF ablation treatment
and are waiting for this procedure.
Exclusion Criteria:
• Inability to consent for any reason.
• Inability to have the endoscopy follow up for any reason.
• Those in extremities of age (<18 or >85) will not be recruited.
• Those with a history of upper gastrointestinal tract bleeding or at risk of trauma e.g. esophageal varices or stricture which means there is a contraindication for instrumentation of the esophagus for any reason during the ablation.
Device: ensoETM. Esophageal cooling during AF ablation, Device: Esophageal temperature monitoring probe
AF - Atrial Fibrillation, Complication, Atrio-Esophageal Fistula
AF ablation, Radiofrequency, Esophageal thermal injury, atrio-esophageal fistula, Esophageal protection, Esophageal cooling, Esophageal temperature monitoring probe
Liver Cirrhosis Network Cohort Study (LCN-C)
Crystal K Santillanes, MS - lcn@northwestern.edu
NCT05740358
Inclusion Criteria:
* Age ≥ 18 years
* Willing to provide samples at baseline
* Cirrhosis
Where Cirrhosis is defined as:
• At least one liver biopsy within 5 years prior to consent showing either: a) Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis OR
• At least 2 of the following:
• Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilical vein within the past year 2. Liver stiffness: VCTE within one year prior to consent or during Screening ≥12.5 kPa or MRE within one year prior to consent or during Screening ≥5 kPa 3. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening 4. Either: FIB-4\>2.67 or platelets \<150/mL within 6 months prior to consent or during Screening 5. \>5 years METAVIR stage 4 fibrosis or Ishak stage 5-6
Exclusion Criteria:
* Known and documented prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma
* Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence
* Known prior solid organ transplant or bone marrow transplant
* Current participation in active medication treatment trials at the time of consent for LCN Cohort Study
* Prisoners or individuals with more than 180 days incarceration pending due to difficulty with visits
* Bariatric surgery in the last 180 days prior to consent
* Known history of fontan procedure-associated liver disease (FALD)
* Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study or interfere with or prevent follow-up per protocol
* Current liver-unrelated end-stage organ failures (Dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen, current known active malignancy besides non-melanomatous skin cancer or carcinoma in situ)
* Documented history of acute alcohol-associated hepatitis (according to NIAAA criteria as described in the MOP) in the 180 days 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 with 90 days prior to consent
* Documented cardiac cirrhosis
* Known recent (within the last 365 days) or present hepatic decompensation with ascites/hydrothorax (including trace ascites discovered at screening not requiring intervention), hepatic encephalopathy or variceal bleeding. If a patient has had a history of decompensation, they must have been off any medications to treat decompensation for at least 365 days. Refer to the MOP for clarifying details on evaluating eligibility for patients with a history of prior decompensation.
* 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)
* Current model for end-stage liver disease (MELD-Na) cut off ≥ 15\*
* Current Child-Turcotte-Pugh (CTP) B or C\*
* Current known Hepatitis C Virus (HCV) without sustained virologic response (SVR)
* Current known quantifiable Hepatitis B Virus (HBV) viral DNA on therapy with ongoing adherence on suppressive therapy\*
* In patients with autoimmune hepatitis: serum aspartate aminotransferase (AST) \> 2X upper limit of normal (ULN) within 90 days prior to consent or during Screening\*
* In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 90 days prior to consent or during Screening\*
* Indicates an exclusion criterion that may depend on laboratory results and other clinical assessments to be ordered during Screening after confirming the participant is otherwise eligible. If the test was performed as standard-of-care in the 90 days prior to consent, it does not need to be re-done for eligibility. Cirrhosis, Cirrhosis, Liver, Cirrhosis Early, Cirrhosis Due to Hepatitis B, Cirrhosis Advanced, Cirrhosis Infectious, Cirrhosis Alcoholic, Cirrhosis, Biliary, Cirrhosis Cryptogenic, Cirrhosis Due to Hepatitis C, Cirrhosis Due to Primary Sclerosing Cholangitis, Autoimmune Hepatitis
Cirrhosis, Liver, Nonalcoholic Fatty Liver Disease, NASH, Nonalcoholic steatohepatitis
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
ctrrecruit@vcu.edu
PHASE2
NCT05136196
Inclusion Criteria:
* STEP 1 - SPECIMEN SUBMISSION
* Participants must have histologically confirmed melanoma that is stage III or IV, unresectable, recurrent, or metastatic non-uveal melanoma OR Participants must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) that is either locally recurrent and non-amendable to curative therapy (e.g., radiation, surgery) or metastatic. The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible
* Note: For participants with primary oropharyngeal cancer, human papillomavirus (HPV) or p16 status must be known prior to step 1 registration
* Participants must have disease presentation consistent with measurable disease. Note: Current disease measurements will not be required until step 2 registration
* Participants must have had documented progression during or within 12 weeks after the last dose of PD-1 checkpoint inhibition-based therapy. Participants must have been receiving checkpoint inhibition for a minimum of 6 weeks. Participants who recur during adjuvant anti-PD1 treatment or within 12 weeks of completion of adjuvant anti-PD1 treatment are eligible if they have measurable disease and are considered unresectable
* Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test within 6 months prior to step 1 registration
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to step 1 registration
* Participants with a history of hepatitis C virus (HCV) infection must have no detectable viral load within 28 days prior to step 1 registration
* Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV as mentioned above)
* Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days prior to step 1 registration, unless clinically stable with ongoing medical management
* Participants must have recovered to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 toxicities related to any prior treatments, unless adverse events are deemed clinically nonsignificant by the treating investigator or stable on supportive therapy
* Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the mucosal surfaces of the head and neck, with the additional following criteria:
* If the primary radiation is combined with chemotherapy, a minimum of 16 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration. If the radiation is given alone, a minimum of 8 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration
* Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) with the exception of central nervous system (CNS) radiation and must be completed at least 4 weeks prior to step 1 registration
* Treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation
* Participants must not have received prior treatment with anti-VEGF therapies for any reason
* Participants must be \>= 18 years of age
* Participants must have a Zubrod Performance Status 0 or 1
* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better to be eligible for this trial
* Participants must not have any known significant organ disfunction that, in the opinion of the treating investigator, may impact suitability for receiving combination nivolumab/cabozantinib treatment
* Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules
* Participants must not have malabsorption syndrome
* Participants must not have active autoimmune disease requiring systemic steroids (equivalent of \> 10mg of prednisone) or other immune suppression. Exceptions:
* Type 1 diabetes mellitus
* Endocrinopathy only requiring hormone replacement
* Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment
* Conditions not expected to recur in the absence of an external trigger
* Participants must not have received an organ allograft
* Participants must not have a history of hemoptysis (defined as \>= 1/2 tsp of bright red blood per day) or tumor bleeding within 90 days prior to step 1 registration
* Participants must not have any of the following criteria due to the possibility of increased risk for tumor bleeding with cabozantinib therapy:
* Prior carotid bleeding
* Tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies
* Central (e.g., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies
* Any prior history of bleeding related to the current head and neck cancer
* History of gross hemoptysis (bright red blood of 1/2 teaspoon or more per episode of coughing) within 3 months
* Participants must not require concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)
* Participants must not require anticoagulants except for the following:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors, rivaroxaban, edoxaban, or apixaban in participants without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to step 1 registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
* Participants must not have evidence of preexisting uncontrolled hypertension 28 days prior to step 1 registration as documented by baseline blood pressure reading with systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 90 mmHg. Participants on antihypertensive therapies with controlled blood pressure are eligible
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing due to the known safety profiles of the drugs in this study. 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
* Have an adequate archival tissue specimen verified by the local pathologist and documented on the Pathology Review Form from a procedure obtained after the development of resistance to anti-PD-1/L1 therapy. Archival tissue must consist of tumor block or at least 1 hematoxylin and eosin (H\&E)-stained 4-5 micron slide and 20 freshly cut serially sectioned and numbered 4-5 micron unstained, uncharged slides OR
Be willing to undergo research biopsy AND have tumor accessible for biopsy based on the following criteria:
* Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies can be obtained incidentally to a clinically necessary procedure and NOT for the sole purpose of the clinical trial
* Acceptable biopsy procedures are:
* Percutaneous biopsy with local anesthetic and/or sedation with an expected risk of severe complications \< 2%
* Direct transoral biopsy (with or without local anesthetic and/or sedation) with an expected risk of severe complications \< 2%
* Excisional cutaneous biopsy with local anesthetic and/or sedation with an expected risk of severe complications \< 2%
* Biopsy with removal of additional tumor tissue during a medically necessary mediastinoscopy, laparoscopy, gastrointestinal endoscopy, bronchoscopy or craniotomy. No open surgical, laparoscopic or endoscopic procedure should be performed solely to obtain a biopsy for this protocol
* Removal of additional tumor tissue during a medically necessary surgical procedure
* Participants must submit whole blood for germline genomic analysis
* Participants must have been offered the opportunity to participate in specimen banking
* Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
* STEP 2 TREATMENT REGISTRATION
* Note: No tests or exams are required to be repeated for step 2 registration (Treatment). However, participants who are known to have a change in eligibility status after step 1 registration are not eligible for step 2 registration
* Participants must continue to meet eligibility for step 1 registration prior to step 2 registration
* Participants must have had their tumor tissue submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System prior to step 2 registration
* Participants registered during stage II of the protocol must have received assignment to an open cohort from the SWOG Statistics and Data Management Center based on their biomarker screening profile (not applicable for patients registered during stage I of the protocol)
* Participants must have measurable disease. All measurable disease must be assessed within 28 days prior to step 2 registration. All non-measurable disease must be assessed within 42 days prior to step 2 registration. Note: All disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1)
* For melanoma participants, CT chest, abdomen and pelvis must be obtained. For HNSCC participants, CT neck and chest must be obtained. Further imaging (i.e., MR brain, CT abdomen/pelvis or extremities, bone scan) will be performed as deemed appropriate by the treating physician
* Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy
* Participants must not have experienced any significant health changes that, in the opinion of the treating investigator, may impact continued suitability for receiving combination nivolumab/cabozantinib treatment
* Participants with treated brain metastases must have discontinued steroid treatment at least 14 days prior to step 2 registration
* Participants must not have received investigational agents or monoclonal antibodies (except Food and Drug Administration \[FDA\] approved supportive care antibodies, such as denosumab) within 28 days prior to step 2 registration
* Participants must not have received surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to step 2 registration
* Participants must not have received administration of a live, attenuated vaccine within 30 days prior to step 2 registration. Note: Participants may have received a messenger ribonucleic acid (mRNA) or viral vector-based coronavirus disease 2019 (COVID-19) vaccine within 30 days prior to step 2 registration
* Participants must not have received administration of any strong CYP3A4 inducers, such as but not limited to rifampin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John's wort, within 14 days prior to step 2 registration
* Participants must not have received administration of any strong CYP3A4 inhibitors, such as but not limited to clarithromycin, itraconazole, ketoconazole, grapefruit juice, indinavir, nelfinavir, ritonavir, nefazodone, saquinavir, and telithromycin, within 5 times the half-life of the CYP3A inhibitor prior to step 2 registration
* Participants must have a history and physical examination performed within 28 days prior to step 2 registration
* Leukocytes \>= 3,000/uL (within 28 days prior to step 2 registration)
* Absolute neutrophil count \>= 1,500/uL (within 28 days prior to step 2 registration)
* Platelets \>= 100,000/uL (within 28 days prior to step 2 registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) or =\< 3 x ULN for participants with Gilbert's disease (within 28 days prior to step 2 registration)
* Aspartate aminotransferase (AST) =\< 3 x institutional ULN (within 28 days prior to step 2 registration)
* Alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 28 days prior to step 2 registration)
* Urinalysis: For baseline value (no required value for eligibility)
* Measured (OR calculated) creatinine clearance \>= 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to step 2 registration PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Locally Recurrent Head and Neck Squamous Cell Carcinoma, Locally Recurrent Hypopharyngeal Squamous Cell Carcinoma, Locally Recurrent Laryngeal Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oropharyngeal Squamous Cell Carcinoma, Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma, Metastatic Laryngeal Squamous Cell Carcinoma, Metastatic Melanoma, Metastatic Oral Cavity Squamous Cell Carcinoma, Metastatic Oropharyngeal Squamous Cell Carcinoma, Recurrent Melanoma, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Unresectable Melanoma