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A Study of OCE-205 in Participants With Cirrhosis With Ascites Who Developed Hepatorenal Syndrome-Acute Kidney Injury
Clinical Operations - clinicaltrials@ocelotbio.com
NCT05309200
Inclusion Criteria:
• Signed informed consent form (ICF) by participant or their legal/authorized representatives.
• Diagnosed with decompensated cirrhosis with ascites.
• Receiving albumin and has had appropriate diuretic withdrawal for at least 2 days prior to randomization into the study.
• Beta-blockers should be discontinued 48 hours prior to randomization, unless doctor deems necessary for appropriate medical treatment.
• No sustained improvement in renal function after both diuretic withdrawal and plasma volume expansion with albumin.
• Female participants must have a negative pregnancy test prior to randomization and agree to avoid becoming pregnant during the study and for 30 days after the end of treatment. Male participants must agree to use 2 effective contraceptive methods during the study and up to 30 days after the end of treatment.
Exclusion Criteria:
• Serum Creatinine >3.8 mg/dL.
• Large volume paracentesis (LVP ≥6L) within 4 days of randomization.
• Pulse oximeter reading of <90% on 2L or less.
• Sepsis and/or uncontrolled bacterial infection.
• Experienced shock within 72 hrs prior to screening.
• Model for End-Stage Liver Disease (MELD) score >35.
• Hypertension with a Systolic BP > 140 mmHg and/ or a Diastolic BP >100 mmHg.
• Treated with or exposed to nephrotoxic agents or has had exposure to radiographic contrast agents within 72 hrs prior to screening.
• Has superimposed acute liver injury due to drugs, or toxins except for acute alcoholic hepatitis.
• Proteinuria greater than 500 mg/dL.
• Impaired cardiac function as evidenced by symptoms consistent with New York Heart Association Classification Class 2 or worse.
• Received Renal Replacement Therapy (RRT) within 4 weeks of randomization.
• Has had a Trans Jugular Intrahepatic Porto-systemic shunt (TIPS).
• Pregnant or breastfeeding.
• Diagnosed with a malignancy within the past 5 years.
• History or current evidence of any condition (COVID-19 positive with respiratory/cardiac complications), therapy or laboratory abnormality that might confound the results of the study, interfere with the participation for the full duration of the study, or is not in the best interest to participate in the opinion of the investigator.
• Participated in a study of an investigational medical product or device within the last 8 weeks preceding screening.
• Experienced a major blood loss (≥500 mL) within the last 4 weeks prior to screening.
• Is stuporous or comatose at screening (West Haven scores III and IV). exhibiting bradycardia.
Drug: OCE-205, Drug: Placebo
Cirrhosis, Ascites, Hepatorenal Syndrome, Acute Kidney Injury
HRS-AKI
Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT)
Jasmohan S Bajaj, MD - jasmohan.bajaj@vcuhealth.org
NCT05548452
Inclusion Criteria:
-\>18 years of age
* Advanced liver disease
* Able to give written, informed consent
* Alcohol as a cause of advanced liver disease
* Continued sustained drinking
* Having previously declined a referral to traditional AUD therapy services or having failed such treatments
Exclusion Criteria:
* Lack of sustained drinking
* Recent or current alcoholic hepatitis
* Alcohol withdrawal symptoms
* Clinically significant use of illicit drugs
* Uncontrolled mood disorders or primary psychotic conditions
* MELD score\>17
* Unclear diagnosis of chronic liver disease
* Current hepatic encephalopathy on lactulose and/or rifaximin
* WBC count\<1000
* Non-elective hospitalization within last month
* on dialysis
* known untreated, in-situ luminal GI cancers
* chronic intrinsic GI diseases (ulcerative colitis, Crohn's disease or microscopic colitis, eosinophilic gastroenteritis and celiac disease)
* Dysphagia within 2 weeks
* History of aspiration, gastroparesis, intestinal obstruction
* Ongoing absorbable antibiotic use
* Severe anaphylactic food allergy
* allergy to ingredients Generally Recognized As Safe in the G3 capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil)
* Adverse event attributable to prior IMT
* ASA Class IV or V
* Pregnant or nursing patients
* acute illness or fever on the day of planned FMT
* Immunosuppression
* Other conditions which make patients are poor candidate for this study per investigator judgement DRUG: Intestinal Microbiota Transplant (IMT) Capsules, DRUG: Placebo Capsules
Liver Disease, Alcohol-Related, Cirrhosis, Alcohol Use Disorder
Intestinal Microbiota Transplant, Alcohol Use Disorder, Cirrhosis, Chronic Liver Disease
A Study to Evaluate the Safety and Efficacy of CNTX-6970 in Subjects With Knee Osteoarthritis Pain.
Aderonke Pederson, MD - apederson@mgh.harvard.edu
NCT05025787
A subject will be eligible for study participation if they meet all of the following
criteria:
• Individuals between 40 and 90 years of age (inclusive) at the time of the Screening Visit.
• Willing to use a mobile smart device during the study period. Individuals who do not have access to a mobile device will be provided with one for the duration of the study and trained in its use.
• Can understand the nature of the study and protocol requirements and is willing to comply with study drug administration requirements and discontinue prohibited concomitant medications.
• Radiography of both knees with a posterior-anterior, fixed-flexion view taken during the Screening visit. The Index knee must show evidence of chronic OA with a K-L Grading Scale of 1, 2, 3, or 4. Such evidence will be provided by a central reading of the radiography of both knees from an expert radiologist of the CCC of EPPIC-Net.
• Moderate to severe pain in the Index knee associated with OA and stable for a minimum of 6 months prior to Screening in the opinion of the investigator.
• Confirmation of OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria.
• Subjects must have failed 2 or more prior therapies. Failure is deemed to be inadequate relief in the opinion of the investigator.
• Body mass index (BMI) of ≤ 40 kg/m2.
• Willing to refrain from illicit drug use during the study, and to have illicit drug testing at screening and at later time points. A subject will be excluded from the study if they meet any of the following criteria:
• Any form of joint replacement surgery, open surgery, or arthroscopic surgery of the index knee/knee joint with 12 months of Screening.
• Any painful condition(s) of the index knee due to disease other than OA. For example, periarticular or referred pain involving the index knee, or from joint disease other than OA associated with the index knee.
• Other chronic pain anywhere in the lower extremities (e.g. hips, legs, feet) that is equal or greater in intensity or impairment than index knee pain or that requires the use of analgesic medications. This includes radicular low back pain with radiation to the knee.
• Documented history of neuropathic arthropathy in the knee.
• Significant instability (e.g., cruciate ligament tear or rupture or previous repair) within the past 5 years or current misalignment (>10 degrees varus or valgus) of the index knee.
• Plans to have surgery, invasive procedures, or intra-articular (IA) injections of the index knee or procedure or surgery otherwise contraindicated for study participation while in the study. a. Concomitant Medications for Pain - i. Continuous use of one of the following medications prescribed for pain: tramadol, gabapentin, duloxetine, pregabalin, milnacipran, or tricyclic antidepressants that is:
• chronic for at least 12 weeks; and
• at a stable dose for at least 4 weeks before Screening ii. Intermittent use of opioids that is:
• ongoing for at least 4 weeks before Screening;
• at a frequency no more than 4 days/week; and
• not be taken within 24 hours of a study visit iii. As needed use of acetaminophen b. Concomitant Medications for Non-Pain Indications That May Impact Pain - i. Continuous use of medication for non-pain indications that are known to potentially impact pain, e.g. duloxetine for depression, that is at a stable dose for at least 12 weeks prior to Screening.
• Corticosteroid injection in the index knee within 90 days of Screening or during study participation.
• Received IA viscosupplementation (e.g., Synvisc®, Hyalgan®) within 90 days of Screening or any time during study participation.
• History of clearly documented allergic reaction to celecoxib (Celebrex®), or to sulfa drugs.
• Use of an investigational medication within 30 days of Screening, or 5 pharmacokinetic or pharmacodynamic half-lives (whichever is longer) or scheduled to receive such an agent while participating in the current study.
• Current therapy with any immunosuppressive therapy, including corticosteroids (>5 mg/day of prednisone).
• Individuals between 40 and 90 years of age (inclusive) at the time of the Screening Visit.
• Willing to use a mobile smart device during the study period. Individuals who do not have access to a mobile device will be provided with one for the duration of the study and trained in its use.
• Can understand the nature of the study and protocol requirements and is willing to comply with study drug administration requirements and discontinue prohibited concomitant medications.
• Radiography of both knees with a posterior-anterior, fixed-flexion view taken during the Screening visit. The Index knee must show evidence of chronic OA with a K-L Grading Scale of 1, 2, 3, or 4. Such evidence will be provided by a central reading of the radiography of both knees from an expert radiologist of the CCC of EPPIC-Net.
• Moderate to severe pain in the Index knee associated with OA and stable for a minimum of 6 months prior to Screening in the opinion of the investigator.
• Confirmation of OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria.
• Subjects must have failed 2 or more prior therapies. Failure is deemed to be inadequate relief in the opinion of the investigator.
• Body mass index (BMI) of ≤ 40 kg/m2.
• Willing to refrain from illicit drug use during the study, and to have illicit drug testing at screening and at later time points. A subject will be excluded from the study if they meet any of the following criteria:
• Any form of joint replacement surgery, open surgery, or arthroscopic surgery of the index knee/knee joint with 12 months of Screening.
• Any painful condition(s) of the index knee due to disease other than OA. For example, periarticular or referred pain involving the index knee, or from joint disease other than OA associated with the index knee.
• Other chronic pain anywhere in the lower extremities (e.g. hips, legs, feet) that is equal or greater in intensity or impairment than index knee pain or that requires the use of analgesic medications. This includes radicular low back pain with radiation to the knee.
• Documented history of neuropathic arthropathy in the knee.
• Significant instability (e.g., cruciate ligament tear or rupture or previous repair) within the past 5 years or current misalignment (>10 degrees varus or valgus) of the index knee.
• Plans to have surgery, invasive procedures, or intra-articular (IA) injections of the index knee or procedure or surgery otherwise contraindicated for study participation while in the study. a. Concomitant Medications for Pain - i. Continuous use of one of the following medications prescribed for pain: tramadol, gabapentin, duloxetine, pregabalin, milnacipran, or tricyclic antidepressants that is:
• chronic for at least 12 weeks; and
• at a stable dose for at least 4 weeks before Screening ii. Intermittent use of opioids that is:
• ongoing for at least 4 weeks before Screening;
• at a frequency no more than 4 days/week; and
• not be taken within 24 hours of a study visit iii. As needed use of acetaminophen b. Concomitant Medications for Non-Pain Indications That May Impact Pain - i. Continuous use of medication for non-pain indications that are known to potentially impact pain, e.g. duloxetine for depression, that is at a stable dose for at least 12 weeks prior to Screening.
• Corticosteroid injection in the index knee within 90 days of Screening or during study participation.
• Received IA viscosupplementation (e.g., Synvisc®, Hyalgan®) within 90 days of Screening or any time during study participation.
• History of clearly documented allergic reaction to celecoxib (Celebrex®), or to sulfa drugs.
• Use of an investigational medication within 30 days of Screening, or 5 pharmacokinetic or pharmacodynamic half-lives (whichever is longer) or scheduled to receive such an agent while participating in the current study.
• Current therapy with any immunosuppressive therapy, including corticosteroids (>5 mg/day of prednisone).
Drug: Celecoxib, Drug: CNTX-6970, Drug: Placebo
Knee Osteoarthritis
IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Advanced Melanoma (IOB-013 / KN-D18)
Eva Ehrnrooth Chief Medical Officer, MD, PhD - ee@iobiotech.com
NCT05155254
Inclusion Criteria:
• Histologically or cytologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer 8th edition guidelines not amenable to local therapy
• Patients are treatment naive, that is, no previous systemic anticancer therapy for unresectable or metastatic melanoma. For clarification, the following patients are eligible:
• Patients with proto-oncogene B-Raf (BRAFV600) mutation-positive melanoma are eligible if treatment naive and without rapidly progressive disease as per investigator assessment.
• Patients who have received previous adjuvant and/or neoadjuvant therapy with targeted therapy or immune therapy are eligible if administered the last dose at least 6 months before inclusion in this trial (randomization), and if relapse did not occur during active treatment or within 6 months of treatment discontinuation.
• At least 1 measurable lesion (not a cutaneous lesion) according to response evaluation criteria for solid tumors (RECIST v1.1) and confirmed by IRC.
• Provision of archival (obtained within 3 months), or newly acquired biopsy tissue not previously irradiated, and blood at screening for biomarker assessments. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
Exclusion Criteria:
• Patients with known or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease are excluded with the following exception: • Patients with controlled (stable) brain metastases will be allowed to enroll (subject to baseline magnetic resonance imaging (MRI) confirmation). Controlled (stable) brain metastases are defined as those with no radiographic progression for at least 4 weeks after radiation and/or surgical treatment at the time of signed informed consent. Patients must have been off steroids for at least 2 weeks before signed informed consent and have no new or progressive neurological signs and symptoms.
• Patient has received previous radiotherapy within 2 weeks of start of trial treatment (visit 2). Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Patients with BRAFV600-positive disease who are experiencing rapidly progressing disease and/or have received standard first-line therapy with BRAF and/or MEK inhibitor for unresectable or metastatic disease. Other protocol defined inclusion/exclusion criteria may apply.
Drug: IO102-IO103, Drug: Pembrolizumab
Metastatic Melanoma, Unresectable Melanoma
Metastatic melanoma, Unresectable melanoma, Immunotherapy, Progression free survival, IO102-IO103, Pembrolizumab
Melanoma Margins Trial-II: 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma (MelMarT-II)
Melanoma and Skin Cancer Trials Coordinator - melmart@masc.org.au
NCT03860883
Inclusion Criteria:
Patients may be included in the study if they meet ALL of the following criteria:
• 1. Patients must have a Stage II primary invasive cutaneous melanoma (pT2b-pT4b, AJCC 8th edition) with Breslow thickness \>1.0mm to 2.0mm; \>2.0mm to 4.0mm or \>4.0mm with ulceration, or \>2.0mm to 4.0mm; or \>4.0mm without ulceration (Table 1) as determined by diagnostic biopsy (narrow excision, incision, shave or punch biopsy) and subsequent histopathological analysis.
• Must have a primary melanoma that is cutaneous (including head, neck, trunk, extremity, scalp, palm or sole).
• An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary melanoma.
• 4. Surgical intervention (which refers to the staging -SLNB and WLE as these are both to be done on the same day) must be completed within 120 days of the original diagnosis. Surgical intervention must also be performed within 28 days of randomisation.
• Patients must be 18 years or older at time of consent.
• Patient must be able to give informed consent and comply with the treatment protocol and follow up plan.
• Life expectancy of at least 5 years from the time of diagnosis, not considering the melanoma in question, as determined by the PI.
• Patients must have an ECOG performance score between 0 and 1 at screening.
• A survivor of prior cancer is eligible provided that ALL of the following criteria are met and documented: * The patient has undergone potentially curative therapy for all prior malignancies, * There has been no evidence of recurrence of any prior malignancies for at least FIVE years (with the exception of successfully treated uterine/cervical or non-melanoma skin cancers (SCCs/BCCs) with no evidence of recurrence), and * The patient is deemed by their treating physician to be at low risk of recurrence from previous malignancies.
Exclusion Criteria:
Patients will be excluded from the study for ANY of the following reasons:
• Uncertain diagnosis of melanoma i.e., so-called 'melanocytic lesion of unknown malignant potential'.
• Patient has already undergone WLE at the site of the primary index lesion.
• Patient unable or ineligible to undergo staging SLNB of the primary index lesion.
• Perineural invasion or neurotropic melanoma: Neurotropism or perineural invasion in any type of melanoma is an exclusion. Perineural invasion does not include entrapment of nerves within the main primary tumour mass.
• Desmoplastic melanoma: with any patient where pathology determines melanoma as PURE desmoplastic (as per WHO definition of \>90% desmoplasia), they are not eligible for this study. However melanomas with less than 90% desmoplasia or mixed desmoplastic subtypes are eligible unless there is neurotropism present (perineural invasion).
• Microsatellitosis (a nest of metastatic tumour cells found to be growing away from the primary tumour) as per AJCC 8th edition definition is an exclusion.
• Subungual melanoma
• Patient has already undergone a local flap reconstruction of the defect after excision of the primary and determination of an accurate excision margin is impossible.
• History of previous or concurrent (i.e. \>1 primary melanoma) invasive melanoma.
• Melanoma located distal to the metacarpophalangeal joint; on the tip of the nose; the eyelids or on the ear; genitalia, perineum or anus; mucous membranes or internal viscera.
• Physical, clinical, radiographic or pathologic evidence of satellite, in-transit, regional, or distant metastatic melanoma.
• Patient has undergone surgery on a separate occasion to clear the lymph nodes of the probable draining lymphatic field, including -SLNB, of the index melanoma.
• Any additional solid tumour or hematologic malignancy during the past 5 years (with exception of non- melanoma skin cancers (T1 skin lesions of squamous cell carcinoma (SCCs), basal cell carcinoma (BCCs)), or uterine/cervical cancer).
• Melanoma-related operative procedures not corresponding to criteria described in the protocol.
• Planned adjuvant radiotherapy to the primary melanoma site after wide local excision is not permitted as part of the protocol and any patients given this treatment would be excluded from the study.
• History of organ transplantation.
• Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at enrolment or within 6 months prior to enrolment. Pregnancy is not a specific exclusion criterion for this trial, though it may not be clinically appropriate to perform a wide excision and SLNB until the pregnancy has been completed, which may exclude the patient due to violation of inclusion criterion 4. We would advise careful counselling of the patient prior to enrolling the patient, which would include a discussion at the treating centre's multidisciplinary team meeting or tumour board. We would strongly advise contacting the central trial office to discuss the case prior to enrolling on the study.
PROCEDURE: Wide Local Excision = 1cm Margin, PROCEDURE: Wide Local Excision = 2cm Margin
Cutaneous Melanoma, Stage II
Malignant, Melanoma, Cancer, Surgery
A Study of Comparing Talquetamab to Belantamab Mafodotin in Participants With Relapsed/Refractory Multiple Myeloma (MonumenTAL-5)
Study Contact - Participate-In-This-Study@its.jnj.com
NCT05461209
Inclusion Criteria:
• Documented multiple myeloma as defined by the criteria: a) multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria b) measurable disease at screening, as assessed by central laboratory, defined by any of the following i) serum M-protein level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) ii) urine M-protein level >=200 milligram (mg)/24 hours iii) Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum free light chain (sFLC) >=10 milligram per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain (FLC) ratio
• Received at least 4 prior antimyeloma therapies including an anti-cluster of differentiation 38 (CD38) monoclonal antibody (mAb) (alone or in combination) and is refractory per IMWG criteria to at least one proteasome inhibitor (PI), and one immunomodulatory drug (IMiD)
• Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at screening
• A female participant of childbearing potential must have a negative serum pregnancy test at screening, and must agree to further serum or urine pregnancy tests during the study and within 6 months after receiving the last dose of study treatment
Exclusion Criteria:
• Contraindications or life-threatening known allergies, hypersensitivity, or intolerance to any study drug or its excipients
• Stroke or seizure within 6 months prior to signing informed consent form (ICF)
• Prior or concurrent exposure to belantamab mafodotin
• Current corneal epithelial disease except mild punctate keratopathy
• Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required
Drug: Talquetamab, Drug: Belantamab Mafodotin
Relapsed/ Refractory Multiple Myeloma
NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies
EVP, Clinical Operations and Quality Assurance - clinicaltrials@novita-pharm.com
NCT05023486
Inclusion Criteria:
• Male or female ≥18 years of age;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Life expectancy of \> 6 months;
• Abilty to swallow capsules and tablets;
• Adequate organ and bone marrow function, defined by the following: ANC \>1500 cells/μL; Hemoglobin \>9.0 g/dL; Platelet count \>100,000 cells/μL; Total bilirubin ≤1.5 mg/dL; Albumin ≥3.0 g/dL; Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase ≤2.5 × upper limit of normal (ULN); Creatinine clearance ≥50 mL/min; and Prothrombin time and partial thromboplastin time ≤1.5 × ULN.
• Female patients of childbearing potential must have a negative serum or urine pregnancy test at Screening and within 24 hours (if urine test) or 72 hours (if serum test) before the first dose of NP-G2-044. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and must be negative for the patient to be eligible; Note: A woman is considered to be childbearing potential unless she is postmenopausal (≥1 year without menses and confirmed with a follicle-stimulating hormone \[FSH\] test) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 3 months after the procedure.
• Male patients must be surgically sterile or willing to use a highly effective double-barrier contraception method (e.g., male condom with diaphragm or male condom with cervical cap) upon study entry, while on NP-G2-044, and for a period of at least 4 months following the last dose of NP-G2-044; and
• Able to understand and voluntarily sign a written informed consent form (ICF) and willing and able to comply with protocol requirements. Inclusion Criteria for NP-G2-044 Monotherapy: Patients must meet all the following criteria to receive NP-G2-044 monotherapy in the study:
• Have a histopathologically confirmed advanced or metastatic solid tumor malignancy for which standard therapies are no longer effective, not tolerated or ineligible for the patient to receive;
• Have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1);
• For monotherapy expansion cohort A (after the Mono-RP2D has been identified), patients must have:
• Gynecologic malignancies including ovarian, endometrial/uterine, fallopian tube, cervical, vulvar, and vaginal cancers; or
• Epidermal growth factor receptor (EGFR)-high (2+ or 3+ staining per DAKO criteria or genomic sequencing data showing 3 or more copies of the EGFR gene) triple-negative breast cancer (TNBC).
• For Monotherapy Expansion Cohort B, patient must have advanced or metastatic solid tumors malignancy Inclusion Criteria for NP-G2-044 Combination Therapy Patients must meet the following criteria to receive NP-G2-044 in combination with anti-PD-1 therapy in the study:
• Have measurable disease per RECIST 1.1; For Combination Therapy Expansion Cohort A:
• Patients must meet 1 of the following criteria to enroll in Combination Therapy Expansion Cohort A:
• Have initiated anti-PD-(L)1 therapy in accordance with the package insert and have been receiving the anti-PD-(L)1 therapy for ≥3 months (with therapy currently ongoing) and have stable disease (defined either by post-treatment onset radiographic scan or ≥3 months without radiographic or clinical evidence of progression), or had an initial period of stable disease and now have an initial scan demonstrating progressive disease per RECIST 1.1. or
• Have discontinued prior anti-PD-(L)1 therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD-1 therapy. For Combination Therapy Expansion Cohorts B through E:
• Patients must meet 1 of the following criteria to enroll in Combination Therapy Expansion Cohorts B through E:
• Have initiated anti-PD-(L)1 therapy. in accordance with the package insert and have been receiving the anti-PD-(L)1 therapy for \>3 months (with therapy currently ongoing) and have stable disease (as defined above), or had an initial period of stable disease or response and now have an initial scan demonstrating progressive disease per RECIST 1.1; or
• Have confirmed progressive disease and discontinued prior anti-PD-(L)1 therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD-1 therapy.
• For Combination Therapy Expansion Cohort B, patients must have cutaneous squamous cell carcinoma (CSCC) (human papilloma virus \[HPV\]-positive or -negative; documentation of HPV status is required);
• For Combination Therapy Expansion Cohort C, patients must have either:
• Esophageal squamous cell carcinoma (ESCC) (HPV-positive or -negative; documentation of HPV status is required); or
• Oropharyngeal squamous cell carcinoma (OPSCC) (HPV-positive or -negative; documentation of HPV status is required).
• For Combination Therapy Expansion Cohort D, patients must have non muscle invasive bladder cancer (NMIBC) meeting Bacillus Calmette-Guérin (BCG)-unresponsive criteria;
• For Combination Therapy Expansion Cohort E, patients must have microsatellite instability high (MSI-H) cancer; For Combination Therapy Expansion Cohorts F and G:
• For Combination Therapy Expansion Cohort F, patients must be immunotherapy naïve (I O naïve), have pancreatic ductal adenocarcinoma (PDAC), and meet the following criteria:
• Have had stable disease or response with at least 4 months of standard of care chemotherapy;
• Have no liver metastasis; and
• Have albumin within the normal range at Screening and \>3.5 g/dL (±10%) 3 days before Cycle 1 Day 1.
• For Combination Therapy Expansion Cohort G, patients must be I O naïve, have platinum resistant ovarian cancer (PROC), and meet the following criteria:
• Had disease recurrence during or within 6 months after last administration of platinum-based chemotherapy; and
• Received no more than 2 prior regimens of systemic therapy after development of platinum resistance.
Exclusion Criteria:
• Received chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of NP-G2-044; Note: Prior immunotherapy is allowed for patients receiving NP-G2-044 monotherapy. For PDAC patients in Combination Therapy Expansion Cohort F: received systemic therapy within 2 weeks of the first dose of NP-G2-044.
• Unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than NCI CTCAE v5.0 Grade ≤2 alopecia or neuropathy) not yet resolved to NCI CTCAE v5.0 Grade ≤1; Note: Patients who experienced a Grade ≥3 anti-PD-1-related AE per NCI CTCAE v5.0 are excluded unless recovered and approved by the Novita Medical Monitor or designee.
• Receiving any other investigational agent(s) or have received an investigational agent within 4 weeks of the first dose of NP-G2-044; Note: Patients who have progressed on NP-G2-044 treatment prior to this study are not eligible
• Known untreated brain metastases or treated brain metastases that have not been radiographically and clinically stable (i.e., not requiring steroids) ≥4 weeks prior to study enrollment;
• QTc by Fridericia method \>470 msec or electrocardiogram (ECG) with evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator;
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements;
• Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during the study or within 90 days after dosing of NP-G2-044;
• Received prior allogenic hematopoietic stem cell transplantation or allogenic bone marrow transplantation;
• Received prior solid organ transplantation;
• Ongoing immunosuppressive therapy (≥10 mg/day of prednisone or its equivalent);
• Requires the use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4, CYP1A2, or CYP2D6 during the study;
• History of clinically meaningful gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study enrollment;
• Excluded by the Sponsor due to medical history, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria; or
• For PDAC patients in Combination Therapy Expansion Cohort F only: have a documented rise in tumor markers within the last 4 months.
DRUG: NP-G2-044 Monotherapy, DRUG: Anti-PD-1 Therapy, DRUG: NP-G2-044 Combination therapy
Advanced or Metastatic Solid Tumor Malignancies
Advanced or Metastatic Solid Tumor Malignancies
A Study of BMS-986253 in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Advanced Cancers
BMS Study Connect Contact Center www.BMSStudyConnect.com - Clinical.Trials@bms.com
NCT03400332
Inclusion Criteria:
• Histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable) with measurable disease per RECIST v1.1
• At least 1 lesion accessible for biopsy
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
Exclusion Criteria:
• Participants with CNS metastases as the only site of active disease (Participants with controlled brain metastases; however, will be allowed to enroll)
• Participants with active, known or suspected autoimmune disease
• Participants with conditions requiring systemic treatment with either corticosteroids (> 10mg prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration
• Participants with a known history of testing positive for Human Immunodeficiency Virus (HIV) or known Acquired Immunodeficiency Syndrome (AIDS)
• Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy Other protocol defined inclusion/exclusion criteria could apply
Drug: BMS-986253, Biological: Nivolumab, Biological: Ipilimumab, Other: Placebo
Cancer, Melanoma
INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Incyte Corporation Medical Information (US and Canada) Call Center (US) - medinfo@incyte.com
NCT05359692
Inclusion Criteria:
• Histologically or cytologically confirmed recurrent or metastatic HNSCC (oral cavity, oropharynx, hypopharynx, or larynx), that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Participants with squamous cell carcinomas of the nasopharynx, salivary gland, or nonsquamous cell histology are excluded.
• Documented progression on or after PD-(L)1 inhibitor alone or in combination with platinum-based chemotherapy for recurrent or metastatic HNSCC. Exception: Treatment Group B (Part 2, expansion): PD-(L)1-naïve.
• ECOG performance status of 0 to 1.
• Measurable disease based on RECIST v1.1.
• Mandatory pre-treatment and on-treatment tumor biopsies.
• GITR-positive tumor confirmed by central laboratory before study treatment start.
• Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
• Have received chemotherapy, targeted small molecule therapy or curative radiation within 21 days of first dose of study drug; prior mAB for anticancer therapy other within 28 days of first dose of study drug; or investigational study drugs or devices within 28 days or five half-lives prior to enrollment unless approved by medical monitor.
• Prior treatment with any TNF Super Family agonist therapy.
• Have not recovered to ≤ Grade 1 from toxic effects of prior therapy.
• Laboratory and medical history parameters not within the Protocol-defined range before the first administration of study treatment. Known active HBV or HCV, or Known to be seropositive for HIV.
• Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Known active infections requiring systemic treatment.
Biological: INCAGN01876, Biological: retifanlimab
Recurrent Cancer, Metastatic Cancer, Advanced Malignancies, Head and Neck Squamous Cell Carcinoma
carcinoma, carcinoma, squamous cell, squamous cell carcinoma of head and neck, anti-PD-(L)1 therapy, HNSCC, SCCHN
Forgotten Voices: Addressing Unmet Needs in Brain Tumor Caregivers (AIM 2)
Kelcie D Willis, M.S. - williskd@vcu.edu
NCT05590273
Inclusion Criteria:
• Caregiver participants must be the caregiver of a brain cancer patient who is currently enrolled in DoD CA200896 (IRBHM20022755)
• Fluent in English
• Willing and able to attend a minimum of 3 CALM sessions via telehealth
• A caregiver is defined as the primary person who provides ongoing support to the brain cancer patient; it is not necessary that the caregiver lives with the patient or is related
• Patient participants must have enrolled in the linked HM20022755 study
Exclusion Criteria:
• Person does not consider themselves to be a caregiver of the patient
• Caregiver does not have a loved one (patient diagnosed with brain cancer) enrolled in DoDCA200896 (IRB HM20022755)
• Caregiver does not speak English
• Caregiver is unable to provide consent
• Caregiver does not have access to telehealth
• Caregiver is under the age of 18
• Professional caregivers who received financial compensation for their services are ineligible
Behavioral: CALM Therapy
Caregivers, Neuro-Oncology, Brain Cancer
CALM
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
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
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
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
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
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
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
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
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
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
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
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
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
* 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.)
* 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
Prophylaxis With Direct-acting Antivirals for Kidney Transplantation From HCV-Infected Donors to Uninfected Recipients (PREVENT-HCV)
Christine Durand, MD - cdurand2@jhmi.edu
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
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
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
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
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
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
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