Paramus, New Jersey

Comparative Effectiveness of Prophylactic ICD Versus Non-ICD Therapy

The proposed CONTEMP-ICD trial is a prospective, multicenter, open-label, randomized controlled trial; enrolling 3290 participants with HFrEF, on stable and optimal guideline-directed medical therapy (GDMT), who are eligible for a primary prevention ICD, but have a low predicted arrhythmic risk. Enrolled participants will be randomized in a 1:1 ratio to non-ICD vs. ICD treatment arms. The investigators hypothesize that, in participants with HFrEF who have a low predicted arrhythmic risk, non-ICD vs. ICD is non-inferior with respect to the primary endpoint of all-cause mortality and superior survival free of major cardiovascular (CV) events. This study will recruit adults 18 years of age and older with heart failure. Participants will be asked to complete questionnaires. Information from medical records will be gathered including medical history, physical exam, medications, blood work results, and imaging. Visits will be at initial, three, six months, and every six months beyond six months. For those who get an ICD device an interrogation will be collected at the visits.

S1803, Lenalidomide +/- Daratumumab/rHuPh20 as Post-ASCT Maintenance for MM w/MRD to Direct Therapy Duration

Clinical Application of Stem Cell Educator Therapy in Alopecia Areata

Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes

The SCE device is made of a hydrophobic material from FDA-approved (USP Class VI) dishes that tightly binds stem cells CB-SCs without interfering with their immune modulating capability. We originally designed a chamber for co-culture of lymphocytes and CB-SCs that included nine discs of the material with a flow pathway and adherent CB-SCs sandwiched between a top cover plate and a bottom collecting plate. In this trial, we are going to use the 12-layer SCE device. The SCE therapy carried a lower risk of infection than a typical blood transfusion, and did not introduce stem cells or reagents into the patients. In addition, CB-SCs have very low immunogenicity, and the CB-SCs cultured in the device are a highly restricted population and contain no CD3+ T cells or other lymphocyte subsets, eliminating the need for human leukocyte antigen (HLA) matching prior to treatment. This innovative approach has the potential to provide CB-SC-mediated immune modulation therapy for multiple autoimmune diseases while mitigating the safety and ethical concerns associated with other approaches such as T1D, type 2 diabetes (T2D), and alopecia areata (AA) in clinics. The relative simplicity of the approach may also provide cost and time savings relative to other approaches.

Testing the Addition of the Drug Relugolix to the Usual Radiation Therapy for Advanced-Stage Prostate Cancer, The NRG Promethean Study

PRIMARY OBJECTIVE: I. Compare conventional radiological progression-free survival (rPFS) for positron emission tomography (PET)-detected, biochemically recurrent, oligometastatic, castration-sensitive prostate cancer patients treated with stereotactic ablative body radiation therapy (SABR) plus placebo versus (vs.) SABR plus relugolix. SECONDARY OBJECTIVES: I. Compare conventional or PET-based radiological progression-free survival (prPFS) between treatment arms. II. Compare patient-reported sexual and hormonal quality of life as assessed by corresponding Expanded Prostate Cancer Index Composite Short Form (EPIC-26) domains between treatment arms. III. Compare other measures of quality of life obtained from the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ5D-5L), European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue instruments between the two treatment arms. IV. Compare time to salvage therapy and time to castration-resistance between treatment arms. V. Compare local progression (SABR-targeted lesion), biochemical progression, distant metastases, prostate cancer-specific mortality, metastasis-free survival, and overall survival between treatment arms. VI. Determine adverse events rates and compare rates between the two treatment arms. EXPLORATORY OBJECTIVE: I. Evaluate genomic and peripheral tissue and blood markers of treatment response. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive placebo orally (PO) once daily (QD) on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone scan, computed tomography (CT), magnetic resonance imaging (MRI), prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT or PET/MRI, and/or fluciclovine F18 PET/CT or PET/MRI at time of disease progression. Patients may optionally undergo urine and blood sample collection throughout the trial. After completion of study treatment, patients are followed up at 9 and 12 months, subsequently every 6 months to month 60, and then annually thereafter or at the time of progression.

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

PRIMARY OBJECTIVES: I. To determine whether men with National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk (UIR) prostate cancer and lower Decipher genomic risk (Decipher score < 0.40) treated with radiation therapy (RT) alone instead of 6 months androgen deprivation therapy (ADT) + RT experience non-inferior rate of distant metastasis. (De-intensification study) II. To determine whether men with NCCN UIR prostate cancer who are in the higher genomic risk (Decipher score >= 0.40) will have a superior metastasis-free survival through treatment intensification with darolutamide added to the standard of RT plus 6 months ADT. (Intensification study) SECONDARY OBJECTIVES: I. To compare overall survival (OS) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. II. To compare time to prostate specific antigen (PSA) failure between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. III. To compare metastasis free survival (MFS) based on conventional imaging between the standard of care (RT plus 6 months of ADT) and de-intensification intervention (RT alone). IV. To compare MFS based on either conventional and/or molecular imaging between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. V. To compare cumulative incidence of locoregional failure based upon conventional imaging and/ or biopsy between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months ADT plus darolutamide) interventions. VI. To compare cumulative incidence of distant metastasis based upon conventional imaging between standard of care (RT plus 6 months of ADT) and intensification intervention (RT plus 6 months ADT plus darolutamide). VII. To compare cumulative incidence of distant metastasis based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. VIII. To compare prostate cancer-specific mortality between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. IX. To compare sexual and hormonal related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. X. To compare fatigue, as measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. XI. To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. EXPLORATORY OBJECTIVES: I. To compare changes in cardio-metabolic markers, including body mass index, lipids, blood glucose, complete blood count (CBC), comprehensive metabolic panel (CMP), and hemoglobin (Hgb) A1c, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. II. To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. III. To compare cumulative incidence of locoregional failure based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. IV. To compare castrate-resistant prostate cancer (CRPC) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. V. To compare bowel and urinary function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. VI. To compare time to testosterone recovery (defined as a T > 200ng/dL) between the standard of care (RT plus 6 months of ADT) and intensification (RT plus 6 months of ADT plus darolutamide) interventions. VII. To compare health utilities, as measured by the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions. VIII. To develop and assess a machine learning/artificial intelligence algorithm for radiotherapy planning and/or quality assurance. IX. To perform future translational correlative studies using biological data, Decipher results, and clinical outcomes. OUTLINE: DE-INTENSIFICATION STUDY: Patients with Decipher score < 0.40 are randomized to 1 of 2 arms. ARM I: Patients undergo radiation therapy (RT) using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo RT as Arm I. Patients also receive androgen deprivation therapy (ADT) consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days. INTENSIFICATION STUDY: Patients with Decipher score >= 0.40 are randomized to 1 of 2 arms. ARM III: Patients receive treatment as in Arm II. ARM IV: Patients receive RT and ADT as in Arm II. Patients also receive darolutamide orally (PO) twice daily (BID). Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3, 6, 12, 24, 36, 48 and 60 months.

Determine Safety & Recommended Phase 2 Dosing of Zeaxanthin Alone or in Combination w/Pembrolizumab in Patients With Metastatic Cancer

The primary purpose of the study is to determine the safety and optimal dosing of zeaxanthin. Effects on tumor growth will also be looked at but as a secondary endpoint. This study will use a 3+3 design which means that 3 people will receive a certain dose of zeaxanthin and if well tolerated then the next group of people will receive a higher dose. This dose escalation will continue until the highest dose allowed by the study is reached, or a dose is found that is felt not to be safe. If at a given dose one of the three people develops a severe side effect, then three more people will be treated at that dose. If no additional severe side effects develop, then the dose escalation will continue. If two people at a given dose develop severe side effects, that dose will be considered dose limiting and escalation will stop. The doses of zeaxanthin will be based on weight starting with 2 milligrams of zeaxanthin per kilogram of body weight (mg/kg) followed by 4 mg/kg, 6 mg/kg, and finally 8 mg/kg. If a dose level is found to be unsafe, then a new group of patients will be treated at the midpoint dose between the not tolerated dose and the last tolerated dose. Zeaxanthin is supplied as 50 milligram capsules and a person's dose will be rounded to the nearest 50 milligrams.

Comparing Cooling and/or Compression Approaches of Limbs for Prevention of Chemotherapy-Induced Peripheral Neuropathy

PRIMARY OBJECTIVE: I. To compare the proportion of participants who develop clinically meaningful chemotherapy induced peripheral neuropathy (CIPN) at 12 weeks, in participants treated with taxane-based chemotherapy randomized to cryocompression therapy versus continuous compression therapy versus low cyclic compression therapy. SECONDARY OBJECTIVES: I. To compare trajectories over time (6, 12, 24, and 52 weeks) by intervention study arm in clinically meaningful CIPN. II. To compare mean European Organization for Research and Treatment of Cancer Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC-CIPN-20) sensory neuropathy subscale scores at 12 weeks by intervention study arm. III. To compare differences by intervention study arm at 12 weeks in changes from baseline in objective sensory and motor function tests (Neuropen, tuning fork, Timed Get Up and Go test). IV. To compare the proportion of participants who develop clinically meaningful CIPN at 12 weeks in a sensitivity analysis with dropouts treated as failures. V. To compare rates of adverse events related to study device at 12 weeks (including cold intolerance, skin changes, other adverse events [AEs] as assessed by Common Terminology Criteria for Adverse Events [CTCAE]) between the three interventions. ADDITIONAL OBJECTIVES: I. To compare the proportion of participants who develop clinically meaningful CIPN separately at weeks 6, 24, and 52. II. To compare the proportion of participants who develop clinically meaningful CIPN at week 12 with additional covariate adjustment for age and body mass index (BMI). III. To compare differences by intervention study arm at 12 weeks in mean EORTC CIPN-20 motor subscale score and autonomic subscale score, and in mean individual Patient-Reported Outcomes Measurement Information System (PROMIS)-29 domain (Physical Functioning, Anxiety, Depression, Fatigue, Sleep Disturbance, Social Functioning, Pain Interference, and Pain Intensity) scores. IV. To compare trajectories over time (6, 12, 24, and 52 weeks) by intervention study arm in mean EORTC CIPN-20 sensory neuropathy subscale score, motor subscale score, and autonomic subscale score; and in mean PROMIS-29 individual domains (Physical Functioning, Anxiety, Depression, Fatigue, Sleep Disturbance, Social Functioning, Pain Interference, and Pain Intensity) scores; and in changes in objective sensory and motor function tests (Neuropen, tuning fork, Timed Get Up and Go test). V. To evaluate the differences by intervention study arm in proportion of participants who develop clinically meaningful CIPN at 12 weeks by chemotherapy regimen. VI. To assess the effect of the intervention in reducing CIPN occurring in the upper extremities and, separately, in the lower extremities. VII. To explore the relationship between duration of intervention received at the prescribed level and outcome, analogous to a dose-delivered analysis in a treatment trial. VIII. To compare rates by study arm of CTCAE Grade 2 or higher sensory and motor neuropathy at 12 weeks. IX. To evaluate tolerability of cryocompression compared to continuous compression therapy and low cyclic compression therapy, as assessed by rate of temperature and/or pressure adjustments, interruptions, and early discontinuation of the device. X. To determine participant satisfaction of cryocompression compared to continuous compression therapy and low cyclic compression therapy, assessed by patient questionnaire. XI. To compare taxane dose-reductions, treatment delays/discontinuation due to CIPN, and relative taxane dose intensity and total taxane dose received, between intervention study arms. XII. To evaluate differences of intervention effect by sex, race, and ethnicity. XIII. To confirm pretreatment biomarkers of CIPN risk (vitamin D) and on-treatment biomarker changes indicative of CIPN severity (Neurofilament light chain, NFL) as well as additional biomarkers of interest generated in S1714 for validation. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 3 arms. ARM 1: Patients undergo cryocompression (cooling plus moderate and low pressure to the arms and legs) for 30-minutes pre-taxane chemotherapy infusion, during taxane chemotherapy infusion, and for 30 minutes after completion of each taxane infusion. Patients may also undergo collection of blood, serum and plasma samples during screening and on study. ARM 2: Patients undergo continuous compression (moderate, steady pressure to the arms and legs) for 30-minutes pre-taxane chemotherapy infusion, during taxane chemotherapy infusion, and for 30 minutes after completion of each taxane infusion. Patients may also undergo collection of blood, serum and plasma samples during screening and on study. ARM 3: Patients undergo low cyclic compression (low pressure that comes and goes to the arms and legs) for 30-minutes pre-taxane chemotherapy infusion, during taxane chemotherapy infusion, and for 30 minutes after completion of each taxane infusion. Patients may also undergo collection of blood, serum and plasma samples during screening and on study.

Comparing the Addition of Radiation Either Before or After Surgery for Patients With Brain Metastases

PRIMARY OBJECTIVE: I. To determine if the time to composite adverse endpoint (CAE) (defined as: 1) local tumor progression within the surgical bed; and/or 2) adverse radiation effect [ARE], the imaging correlate of post-stereotactic radiosurgery [SRS] radiation necrosis; and/or 3) nodular meningeal disease [nMD]) is improved in patients treated with pre-resection SRS to the intact lesion versus those treated with post-resection SRS. SECONDARY OBJECTIVES: I. To assess the trajectory of symptom burden in patients treated with pre-resection SRS to the intact lesion versus those treated to the post-resection surgical cavity as measured by MD Anderson Symptom Inventory for brain tumor (MDASI-BT). II. To determine whether there is improved overall survival (OS) in patients with resected brain metastases who undergo pre-resection SRS compared to patients who receive post-resection SRS. III. To compare rates of ARE, the imaging correlate of radiation necrosis, in patients who receive pre-resection SRS to patients who receive post-resection SRS. IV. To determine whether there is increased time to whole brain radiotherapy (WBRT) in patients who receive pre-resection SRS compared to patients who receive post-resection SRS. V. To assess the trajectory of neuro-cognitive function in patients treated with pre-resection SRS to the intact lesion versus those treated to the post-resection surgical cavity as measured by the Montreal Cognitive Assessment (MoCA). VI. To compare rates of nodular meningeal disease in patients who receive pre-resection SRS to patients who receive post-resection SRS. VII. To compare rates of local recurrence in the resection cavity for patients who receive pre-resection SRS to patients who receive post-resection SRS. VIII. To compare rates of local recurrence of intact, non-index metastases treated with SRS. IX. To compare rates of distant brain failure in patients who receive pre-resection SRS to patients who receive post-resection SRS. X. To assess toxicity in the two treatment arms. EXPLORATORY OBJECTIVE: I. To explore if the type of surgical resection (piece-meal versus [vs.] en-bloc) may be associated with the rate of nodular meningeal disease. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction. ARM II: Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for additional 2 years.

The Sinai Robotic Surgery Trial in HPV-related Oropharyngeal Squamous Cell Carcinoma (SIRS 2.0 Trial)

There has been significant increase in the incidence of oropharynx cancer in North America and Europe. It is now understood that there are two dominant carcinogenic pathways for oropharyngeal squamous cell carcinoma. Environmentally related which is caused mainly by smoking and alcohol, and HPV-related oropharyngeal squamous cell carcinoma (HPVOPSCC). HPVOPSCC now accounts for over 80% of OPC seen in the USA and an increasing fraction of these malignancies in Europe. It has been shown that HPVOPSCC confers an excellent prognosis for intermediate staged disease and this has called into question the rational for aggressive concurrent chemoradiotherapy. High-dose radiotherapy (RT) and chemoradiotherapy (CRT) have substantial impact on local tissues and organ function and result in a significant rate of late mortality and morbidity. Studies are now being designed to reduce the impact of RT and CRT for patients. Recently, a new test has been developed that measures HPV circulating tumor DNA (cfHPVDNA) in the blood. The test has emerged as a promising biomarker for HPVOPSCC, correlating with both treatment response as well as surveillance for cancer recurrence. Data suggests that a negative test in the surveillance period following treatment is highly sensitive and specific for recurrent disease. In this trial, the study will be stratifying p16 positive patients with PCR detectable high-risk (HR) HPV DNA or RNA following TORS into risk groups based on final pathology to determine appropriate treatment intensity. Patients with low- or intermediate-risk pathologic disease and undetectable postoperative cfHPVDNA will receive no adjuvant therapy. This group includes patients with AJCC 7th edition T1-T2N0-2b disease. Patients must have less than four pathologic nodes on final pathology, negative margins, and no contralateral nodes. Perineural or lymphovascular alone is allowed but not in combination. Microscopic extranodal extension (less than or equal to 2 mm) is allowed. Patients cannot be active smokers or have a 20 or greater pack year history of smoking.