Bourg De Peage, France
Brain Oxygen Optimization in Severe TBI, Phase 3
BOOST3 is a randomized clinical trial to determine the comparative effectiveness of two strategies for monitoring and treating patients with traumatic brain injury (TBI) in the intensive care unit (ICU). When a person has a TBI, their injured brain can swell over a period of hours or days. If the brain swells too much, the pressure in the skull increases and becomes dangerous, causing further injury to the brain. To try to prevent this, doctors usually insert a device, an ICP monitor, into the brain through a hole in the skull of people with severe TBI. An ICP monitor measures the pressure inside the skull. Most doctors agree that it is important to measure and prevent high ICP. Patients with injured brains also suffer additional injury to the brain if the amount of oxygen in the brain gets too low. Some doctors also insert a second device, a PbtO2 monitor, in the brain through the same or a second hole in the skull to measure brain tissue oxygen. A PbtO2 monitor measures how much oxygen is in a small area of the brain near the tip of the monitor. Other doctors think this is unnecessary and unhelpful. Both monitoring devices are approved by the US Food and Drug Administration (FDA) and Health Canada for patients with TBI. Both are commonly used. The ICP and PbtO2 goals guided by these monitors are used to help doctors adjust their treatment choices. Treatments include kinds and doses of medications and the amount of intravenous fluids given, ventilator (breathing machine) settings, need for blood transfusions, and other medical care. Each of these treatment decisions is intended to improve outcomes. However, each treatment decision also involves potential risks. Different treatment decisions may result in different risks. This study will also help doctors better understand these risks. This study is funded by the National Institutes of Health because it answers questions important to the care of patients with TBI. This study is a two-arm, single-blind, randomized, controlled, phase III, multi-center trial of ICU monitoring and treatment strategies for patients with severe TBI. It will compare the efficacy of ICU care guided by PbtO2 and ICP monitoring versus monitoring of ICP alone in the first 5 days after injury. Only subjects who have severe TBI and require invasive monitoring, according to Brain Trauma Foundation (BTF) and American College of Surgeons-Trauma Quality Improvement (ACS TQIP) guidelines, will be enrolled. All participants in this study will have both ICP monitors and PbtO2 monitors. Half of the participants will be randomized to an arm that includes treatment informed by PbtO2 and ICP, and half will be randomized to an arm that treats only ICP. The PbtO2 values of those in the ICP only arm will be masked, so that the treating physicians will not be guided by PbtO2 information. Participants in the PbtO2 and ICP arm will have PbtO2 monitored and low measurements treated. Treatments to address physiological goals in both arms will follow a clinical standardization plan. Participants will be followed for 6 months and occurrence of serious adverse events or death will be recorded. Participants will have a follow-up interview to assess their level of recovery approximately 6 months post injury. To reduce the likelihood of imbalance of important prognostic factors between groups, a covariate-adjusted randomization scheme will be used in this study. Adjustment variables are clinical site and probability of a poor outcome as defined by the IMPACT core model.
Phase
N/ASpan
427 weeksSponsor
University of MichiganCamden, New Jersey
Recruiting
Transfusion Requirements in Younger Patients Undergoing Cardiac Surgery
Phase
N/ASpan
244 weeksSponsor
Unity Health TorontoCamden, New Jersey
Recruiting
Managed Problem Solving for ART Adherence and HIV Care Retention Delivered by Community Health Workers
Phase
N/ASpan
178 weeksSponsor
University of PennsylvaniaCamden, New Jersey
Recruiting
T-DM1 and Tucatinib Compared with T-DM1 Alone in Preventing Relapses in People with High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial
PRIMARY OBJECTIVE: I. To determine if the invasive disease-free survival (iDFS) with T-DM1 and tucatinib is superior to the iDFS in the control arm (T-DM1 + placebo) when administered to high risk patients with HER2-positive breast cancer and residual disease after neoadjuvant HER2-directed therapy. SECONDARY OBJECTIVES: I. To evaluate whether treatment with tucatinib plus T-DM1 compared to treatment with T-DM1 alone (T-DM1 plus placebo) improves the following: Ia. Breast cancer free survival (BCFS). Ib. Distant recurrence-free survival (DRFS). Ic. Brain metastases-free survival (BMFS). Id. Overall survival (OS). II. To evaluate whether treatment with tucatinib plus T-DM1 compared to treatment with T-DM1 alone (T-DM1 plus placebo) reduces the incidence of brain metastases. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive T-DM1 intravenously (IV) over 30-90 minutes on day 1 and placebo orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive T-DM1 IV over 30-90 minutes on day 1 and tucatinib PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 6 months for 10 years.
Phase
3Span
744 weeksSponsor
Alliance for Clinical Trials in OncologyCamden, New Jersey
Recruiting
Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer
LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphodepleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.
Phase
2Span
556 weeksSponsor
Iovance Biotherapeutics, Inc.Camden, New Jersey
Recruiting
Staged Complete Revascularization for Coronary Artery Disease vs Medical Management Alone in Patients With AS Undergoing Transcatheter Aortic Valve Replacement
Phase
N/ASpan
276 weeksSponsor
University of British ColumbiaCamden, New Jersey
Recruiting
Nodal Radiation Therapy for Sentinel Lymph Node Positive Melanoma
PRIMARY OBJECTIVE: I. To determine if regional nodal radiation therapy prolongs the time to regional recurrence. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive adjuvant immunotherapy and nodal radiation therapy (30 Gy in 5 treatments over 2-2.5 weeks). GROUP II: Patients receive adjuvant immunotherapy alone. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Phase
2Span
183 weeksSponsor
M.D. Anderson Cancer CenterCamden, New Jersey
Recruiting
Trial of Therapeutic Hypothermia in Patients With ARDS
Brief summary: Acute Respiratory Distress Syndrome (ARDS) is a serious condition that occurs as a complication of medical and surgical diseases, has a mortality of ~40%, and has no known treatment other than optimization of support. Data from basic research, animal models, and retrospective studies, case series, and small prospective studies suggest that therapeutic hypothermia (TH) similar to that used for cardiac arrest may be lung protective in patients with ARDS; however, shivering is a major complication of TH, often requiring paralysis with neuromuscular blocking agents (NMBA) to control. Since the recently completed NHLBI PETAL ROSE trial showed that NMBA had no effect (good or bad) in patients with moderate to severe ARDS, the CHILL trial is designed to evaluate whether TH combined with NMBA is beneficial in patients with ARDS. This Phase IIb randomized clinical trial is funded by the Department of Defense to compare TH (core temperature 34-35°C) + NMBA for 48h vs. usual temperature management in patients in 14 clinical centers with the Clinical Coordination Center and Data Coordinating Center at University of Maryland Baltimore. Planned enrollment is 340 over ~3.5 years of the 4-year contract. COVID-19 is considered an ARDS risk-factor and patients with ARDS secondary to COVID-19 pneumonia will be eligible for enrollment. Primary outcome is 28-day ventilator-free days. Secondary outcomes include safety, physiologic measures, mortality, hospital and ICU length of stay, and serum biomarkers collected at baseline and on days 1, 2, 3, 4, and 7. Background: Despite recent advances in supportive care for patients with acute respiratory distress syndrome (ARDS), mortality remains >40%. Fever worsens and hypothermia mitigates animal models of ALI and in small non-randomized in patients with ARDS. Since hypothermia reduces oxygen utilization as long as shivering is blocked, TH may reduce injury in part by allowing lower levels of assisted ventilation. TH likely exerts additional lung protective effects by directly modifying temperature-dependent cellular processes in endothelium, epithelium, and leukocytes. Neuromuscular blockade (NMB) is the ultimate treatment to block shivering and is frequently used in patients with ARDS to facilitate ventilator management. Since the recently completed NHLBI PETAL ROSE trial showed that NMB caused conferred neither benefit nor harm in patients with moderate to severe ARDS, the investigators have bundled TH with NMB to reduce shivering. An open-label study of 8 ARDS patients showed that studying TH + NMB in patients with moderate to severe ARDS was feasible. Moreover, the patients treated with TH +NMB had more 28-day ventilator-free days (VFDs), ICU-free days (ICU-FDs) and greater hospital survival (75% vs. 25%; p = 0.027) than historical controls with ARDS and NMB but without TH. Within the limits of historical comparisons, these results support further study of TH in ARDS. Since COVID-19 is currently the most common cause of ARDS and will likely remain so for much of the CHILL enrollment period, patients with ARDS secondary to COVID-19 pneumonia are eligible for enrollment in CHILL. Our overall hypothesis is that TH is lung protective in ARDS. The hypothesis to be tested is that induced hypothermia (core temperature 34°-35°C) with NMB to prevent shivering is safe and beneficial in patients with moderate to severe ARDS (PaO2/FIO2 (P/F) ratio≤200) who are receiving NMB. Focus of Study: We will conduct a multicenter RCT pilot of TH+NMB for 48h vs. usual temperature management in 340 patients with ARDS in 14 clinical sites. Primary and secondary objectives: The primary objective is to assess the efficacy and safety of 48h TH+NMB in patients with ARDS compared with a control arm receiving usual temperature management. Secondary objectives include: (1) generating data to inform a decision about whether to proceed with a subsequent civilian population Phase III clinical trial of TH to reduce mortality in ARDS and to direct its study design; (2) analyzing biomarker and physiologic data to determine the mechanism(s) through which TH+NMB might exert benefit in ARDS Study design: The CHILL trial is a multi-center RCT. Intervention: The study intervention is TH to core temperature 34°-35°C + NMB for 48h. Patients in the TH+NMB arm will receive deep sedation, treatment with a neuromuscular blocking agent, and mechanical ventilation for at least 48h. Decisions about transition to unassisted breathing and extubation will be based on criteria in the CHILL study protocol. TH+NMB: Once sedation and NMB are confirmed, TH to 34°-35°C will be initiated using surface cooling. Temperature will be measured from a central probe. Once target temperature is reached, TH will be maintained for 48h. Patients will then be rewarmed to 35.5°C by 0.3°C/h and the cooling devices removed. Post-TH fever suppression is not part of the CHILL protocol and will be performed at the discretion of the primary ICU team. TH+NMB will be aborted for persistent severe bradycardia with hypotension, uncontrolled bleeding, and intractable arrhythmias. Usual temperature management: Patients will receive light sedation (RASS 0 to -1). During the 54h post-randomization treatment period, acetaminophen will be given for core temperature >38°C and surface cooling will be initiated if core temperature remains >38°C within ≥45 minutes of receiving acetaminophen and adjusted to maintain core temperature ≤38°C. If core temperature ≤36°C, patients in this arm will receive surface warming to core temperature 37°C. Following the 54h treatment period, temperature will be managed at the discretion of the primary ICU team. Concomitant Treatment: Proning and corticosteroid therapy is allowed. Primary and Secondary Endpoints: Primary endpoint: 28-day Ventilator-free days (VFDs). Decisions about ventilator weaning and extubation will be made based on criteria in the CHILL protocol. The 28-day VFDs will be calculated at day 28. Intermediate endpoint: The low and high core temperatures in each 2-hour period will be recorded for each of the first four study days. The time required to reach the target temperature and the percent of readings within the target range in the TH+NMB arm will be determined. Secondary endpoints: Clinical: (a) 28-day ICU-FDs: The 28-day ICU-FDs will be calculated at day 28; (b) baseline and day 1, 2, 3, 4, and 7 non-neurologic SOFA score; (c) Glasgow coma score at hospital discharge; (d) 60- and 90-day survival; (e) 60- and 90-day functional status. Physiologic: (a) day-3 and -7 driving pressure; (b) day-3 and day-7 oxygen saturation index (OSI). Plasma Biomarker: Day 0, 1, 2, 3, 4, and 7 plasma will be collected and analyzed in the University of Maryland Cytokine Core Lab using in-house ELISAs (IL-1ß, IL-6, IL-8, IL-18, and sTNFR1) or ELISA kits purchased from R&D Systems (sRAGE, SP-D, sICAM-1, MMP8) and Helena Laboratories (Protein C). Safety: 1. For the first 54h: (a) continuous cardiac monitoring for bradycardia with associated hypotension requiring i.v. fluid or vasopressors; (b) every 6h blood glucose measurement; (c) every 12 h potassium, magnesium and phosphate; (d) significant bleeding event (requiring ≥3u packed red blood cells or surgical or interventional radiologic intervention) 2. For the first 7 days: (a) Ventilator-associated pneumonia (VAP); (b) other secondary infections; (c) monitor for SAEs Schedule of Clinical and Laboratory Evaluations: 1. Definitions: a. Baseline period: 24h prior to randomization b. Comprehensive metabolic panel (CMP): includes basic electrolytes, BUN, creatinine, ALT, AST, alkaline phosphatase, bilirubin, calcium, magnesium, phosphate, C-reactive protein (CRP) c. CBC: complete blood count d. Driving Pressure = Plateau Pressure - PEEP with patient NOT making inspiratory effort (on NMB or post-NMB and observed RR at set ventilator rate) e. OSI = Mean airway pressure x 100 x FIO2/SpO2 2. Clinical and Research laboratory testing: Two purple/pink top tubes (EDTA; 12 ml blood total) will be collected for biomarker analysis just prior to randomization and as close to 0800 as possible on study days 1, 2, 3, 4, and 7 . Clinical laboratory testing required for secondary clinical outcomes at baseline and on study days 1, 2, 3, 4, and will be performed as part of usual clinical care whenever possible). 3. Day -7 to 0 (Screening and enrollment): To facilitate randomization within the inclusion window, we will consent and enroll based on partial fulfillment of randomization criteria and randomize once all criteria are met. Patients between 18 and 75 years old receiving mechanical ventilation for ≤7 days will be screened and those who have bilateral pulmonary opacities not fully explained by pleural effusions, atelectasis, or hydrostatic pulmonary edema and a qualifying P/F ratio (P/F ≤200 with PEEP ≥8) for <72h will be enrolled and randomized. Patients who meet the criteria for pulmonary opacities but have not yet had a qualifying P/F ratio may be enrolled and monitored for potential randomization. 1. Pregnancy testing in women of child-bearing years 2. Obtain informed consent from patient or Legally Authorized Representative (LAR) depending on capacity 3. Complete the screening and enrollment portion of the Screening, Enrollment and Randomization CRF. 4. Enter data into the Medidata CHILL database, which will assign a unique subject ID. 5. The subject ID and patient identifiers are entered into a secure screening log. 3. Randomization: 1. If the patient has had a qualifying P/F ratio at the time of enrollment, proceed with randomization, otherwise follow until the patient has a qualifying P/F ratio, exits the 48h NMBA window or the 7 day mechanical ventilation window, or develops an exclusion. 2. Once patient meets criterion for randomization: i. Obtain baseline plasma for research testing. If >24h since last CBC and CMP, send new samples to lab. ii. Obtain treatment assignment from the automated, web-based randomization service provided by Cooperative Studies Program Coordinating Center (CSPCC). iii. If patient does not have a central temperature probe, place esophageal probe. iv. For TH+NMB arm, confirm adequate sedation (RASS -4 to -5) and NMBA(Train of four ≤2 twitch) and initiate TH protocol using surface cooling as soon as possible. v. Complete the randomization section of the Screening, Enrollment, and Randomization CRF vi. Complete Baseline CRF 4.Day 1-4: 1. Fill out Daily CRFs and enter into Medidata database 2. Collect plasma for research testing. 3. Measure Driving Pressure and OSI 4. Make sure CBC and CMP sent every morning and a subsequent BMP, magnesium, and phosphate sent ~12h later. 5. Rewarming starts 48h after initially reaching target temperature (34°-35°C) on day 3 6. Complete Unassisted Breathing Checklist form if applicable 7. Assess for adverse events 5. Days 5-6: a. Follow for ventilator status, ICU status, survival, SAEs b. Complete Unassisted Breathing Checklist form if applicable c. Assess for adverse events 6. Day 7: 1. Fill out Day 7 CRF and enter into Medidata database 2. Collect plasma for research testing. 3. Measure Driving Pressure and OSI 4. Make sure CBC are CMP sent 5. Complete Unassisted Breathing Checklist form if applicable 6. Assess for adverse events 7. Day 8-27: a. Follow for ventilator status, ICU status, survival, SAEs b. Complete Unassisted Breathing Checklist form if applicable 8. Day 28: 1. Complete Day 28 CRF 2. Calculate 28 day VFDs and ICU-FDs 9. When patient is discharged from the ICU, complete ICU discharge CRF 10. When patient is discharged from the hospital, complete Hospital discharge CRF. 11. Day 60 and 90: Follow up about patient status. Complete phone follow-up CRF. Study population: Adult patients with moderate to severe ARDS based on Berlin criteria (P/F ≤ 200 while on PEEP ≥8 cm H2O) <72h in duration. Data Analysis (see protocol for full description): Primary and secondary analyses will be performed according to the principle of intention-to-treat. The randomization is stratified only by site, which will be accounted for in the primary efficacy analysis. Three interim analyses will be performed after ~25%, ~50%, and ~75% of planned enrollment and a decision to halt the study for efficacy or harm will be made. Primary and Secondary efficacy endpoints will be analyzed using Wilcoxon-Mann-Whitney rank sum test extended to account for stratification by site. Sub-group analysis will test for significant interaction between treatment effect and a priori established baseline characteristics (proning status, shock, COVID, P/F ratio, age, time between meeting ARDS criteria and randomization, and baseline biomarkers (IL-6, bicarb, and protein C)). Data Management (see protocol for full description): Data for this RCT will be recorded on paper CRFs and entered into the Medidata database containing multiple automatic crosschecks. Randomization Plan: Patients will be randomized by the web-based automated system operated by CSPCC using a 1:1 assignment ratio in small blocks of randomly varying size prepared for each site. Subject Participation Duration: The duration of intervention is ~54h including time for cool down and rewarming. Physiologic and clinical parameters will be collected through study day 7. In hospital follow-up will include determination of 28-day VFDs and ICU-FDs, and day of hospital discharge and 60- and 90-day phone follow-up. When the patient regains competence, consent for continued participation will be obtained. Study Duration: Completion of enrollment is anticipated by March 31, 2025 and study completion by July 1, 2025.
Phase
2Span
275 weeksSponsor
University of Maryland, BaltimoreCamden, New Jersey
Recruiting
Two Studies for Patients With High 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 High Gene Risk Score, The PREDICT-RT Trial
PRIMARY OBJECTIVES: I. To determine whether men with National Comprehensive Cancer Network (NCCN) high risk prostate cancer who are in the lower 2/3 of Decipher genomic risk (=< 0.85) can be treated with 12 months androgen deprivation therapy (ADT) plus radiation therapy (RT) instead of 24 months ADT+RT and experience non-inferior metastasis-free survival. (De-intensification study) II. To determine whether men with NCCN high risk prostate cancer who are in the upper 1/3 of Decipher genomic risk (> 0.85) or have node-positive disease by conventional imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) will have a superior metastasis-free survival (MFS) through treatment intensification with apalutamide added to the standard of RT plus 24 month ADT. (Intensification study) SECONDARY OBJECTIVES: I. To compare overall survival (OS) between the standard of care (RT plus 24 months of ADT) and either the de-intensification (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) II. To compare time to prostate specific antigen (PSA) failure or start of salvage treatment between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) III. To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) IV. To compare MFS judged based on either standard or molecular imaging between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) V. To compare prostate cancer-specific mortality between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VI. To compare testosterone levels at the time of PSA failure and metastases between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VII. To compare time to testosterone recovery (defined as a T > 200) between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) VIII. To compare adverse events, both clinician-reported using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and patient-reported using Patient Reported Outcome (PRO)-CTCAE items, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) EXPLORATORY OBJECTIVES: I. To compare changes in cardio-metabolic markers, including body mass index, and waist circumference, between the standard of care (RT plus 24 months of ADT) and either the de-intensification arm (RT plus 12 months of ADT) or intensification arm (RT plus 24 months of ADT plus apalutamide). (De-intensification and intensification studies) II. To develop a machine learning/artificial intelligence algorithm for radiotherapy quality assurance. (De-intensification and Intensification studies) III. To perform future translational correlative studies using biological and imaging data. (De-intensification and intensification studies) IV. Impact of position emission tomography (PET) use, measured by the proportion of times each type of imaging was used, in high-risk prostate cancer. (De-intensification and intensification studies) PATIENT-REPORTED OUTCOMES OBJECTIVES: PRIMARY OBJECTIVES: I. To compare sexual and hormonal function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare fatigue, as measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) SECONDARY OBJECTIVES: I. To compare depression, as measured by the PROMIS-depression, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. To compare depression, as measured by the PROMIS-depression, between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) EXPLORATORY OBJECTIVES: I. 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 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) II. 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 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) III. To compare fatigue, as measured by the PROMIS-Fatigue instrument, between the standard of care (RT plus 24 months of ADT) and the de-intensification arm (RT plus 12 months of ADT). (De-Intensification Study) IV. To compare sexual and hormonal function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) 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 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) VI. 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 24 months of ADT) and the intensification arm (RT plus 24 months of ADT plus apalutamide). (Intensification Study) OUTLINE: Patients are randomized to 1 of 4 arms. DE-INTENSIFICATION STUDY (DECIPHER SCORE =< 0.85): ARM I: Patients undergo radiation therapy (RT) over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 12 months in the absence of disease progression or unacceptable toxicity. INTENSIFICATION STUDY (DECIPHER SCORE > 0.85 OR NODE POSITIVE): ARM III: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix and bicalutamide or flutamide) for 24 months in the absence of disease progression or unacceptable toxicity. ARM IV: Patients undergo RT over 2-11 weeks and receive ADT (consisting of either leuprolide, goserelin, triptorelin, degarelix, buserelin, histrelin, or relugolix) for 24 months in the absence of disease progression or unacceptable toxicity. Patients also receive apalutamide orally (PO) once daily (QD). Treatment repeats every 90 days for up to 8 cycles (24 months) in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan, positron emission tomography (PET) scan, computed tomography (CT) scan, and magnetic resonance imaging (MRI) at screening and as clinically indicated and may optionally undergo blood sample collection throughout the study.
Phase
3Span
676 weeksSponsor
NRG OncologyCamden, New Jersey
Recruiting
Single Fraction or Multi-fraction Palliative Radiation Therapy for the Improvement of Quality of Life in Patients With Metastatic Gynecologic Cancers
PRIMARY OBJECTIVE: I. To determine whether single fraction palliative radiation therapy (SFRT) improves health-related quality of life (HR-QOL) over multi-fraction palliative radiotherapy (MFRT). SECONDARY OBJECTIVES: I. To determine whether single fraction palliative radiation therapy (SFRT) improves individual domains of health-related quality of life (HR-QOL) over multi-fraction palliative radiotherapy (MFRT). II. To determine whether SFRT increases clinically meaningful HR-QOL improvement over MFRT. III. To determine whether SFRT provides non-inferior symptom burden improvement to MFRT. IV. To describe radiation related toxicity rates within 21 days and within year for patients receiving SFRT and MFRT. EXPLORATORY OBJECTIVES: I. To describe T-cell repertoire of patients receiving SFRT and MFRT. II. To describe vaginal microbiome of patients receiving SFRT and MFRT. III. To describe gut microbiome of patients receiving SFRT and MFRT. IV. To describe financial burden of patients undergoing palliative pelvic radiation with either SFRT or MFRT. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients undergo standard of care radiation therapy in the form of 3-dimensional conformal radiation therapy (3D CRT), intensity-modulated radiation therapy (IMRT), or volume modulated arc therapy (VMAT) at the physician's discretion for 1 fraction in the absence of disease progression or unacceptable toxicity. Patients with < 30% decrease in the Symptom Inventory Scale (SIS) may receive an additional fraction on day 21 at the physician's discretion. ARM B: Patients undergo standard of care radiation therapy in the form of 3D CRT, IMRT, or VMAT at the physician's discretion over 2 weeks for 10 fractions in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 1 year.
Phase
2Span
260 weeksSponsor
M.D. Anderson Cancer CenterCamden, New Jersey
Recruiting