REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial
- Conditions
- Interventions
- Registration Number
- NCT06650579
- Lead Sponsor
- Emory University
- Brief Summary
This phase III/IV trial compares the impact of leuprolide and abiraterone acetate (AA) versus relugolix and AA on the heart in hormone-naive patients with advanced prostate cancer receiving pelvic radiation therapy. Leuprolide is in a class of medications called gonadotropin-releasing hormone agonists (GNRHa). It prevents the body from making luteinizing hor...
- Detailed Description
PRIMARY OBJECTIVE:
I. Measure cardiovascular outcomes between combination gonadotropin releasing hormone agonist (GNRHa, i.e. leuprolide) plus abiraterone acetate (AA) versus gonadotropin releasing hormone antagonist (GNRH-antagonist, i.e. relugolix) plus AA in men with advanced prostate cancer receiving definitive radiation therapy.
SECONDARY OBJECTIVES:...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Male
- Target Recruitment
- 72
- Men ≥ 18 years old
- Non-metastatic prostate cancer
- Non-metastatic, biochemically recurrent prostate cancer
- Plan to undergo curative-intent pelvic radiation therapy (photons or protons) with or without brachytherapy
- Plan to undergo up to 24 months of combination androgen deprivation therapy (ADT) plus AA and prednisone
- Metastatic prostate cancer requiring indefinitive ADT or chemotherapy
- Prior exposure to androgen deprivation therapy
- Prior exposure to chemotherapy, immunotherapy, or radiation therapy
- History of cardiac bypass surgery or percutaneous coronary intervention
- History of cardiac pacemaker or defibrillator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (leuprolide plus abiraterone acetate/prednisone) Abiraterone Acetate Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm I (leuprolide plus abiraterone acetate/prednisone) Bicalutamide Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm I (leuprolide plus abiraterone acetate/prednisone) Biospecimen Collection Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm I (leuprolide plus abiraterone acetate/prednisone) Computed Tomography Angiography Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm I (leuprolide plus abiraterone acetate/prednisone) Leuprolide Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm I (leuprolide plus abiraterone acetate/prednisone) Prednisone Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm I (leuprolide plus abiraterone acetate/prednisone) Radiation Therapy Patients receive leuprolide IM or SC injections every 3 to 6 months plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm II (relugolix + abiraterone acetate/prednisone) Abiraterone Acetate Patients receive oral relugolix daily plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm II (relugolix + abiraterone acetate/prednisone) Biospecimen Collection Patients receive oral relugolix daily plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm II (relugolix + abiraterone acetate/prednisone) Computed Tomography Angiography Patients receive oral relugolix daily plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm II (relugolix + abiraterone acetate/prednisone) Prednisone Patients receive oral relugolix daily plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm II (relugolix + abiraterone acetate/prednisone) Radiation Therapy Patients receive oral relugolix daily plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy. Arm II (relugolix + abiraterone acetate/prednisone) Relugolix Patients receive oral relugolix daily plus oral abiraterone acetate (AA) with prednisone daily for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo standard of care radiation therapy.
- Primary Outcome Measures
Name Time Method Incidence of ambulatory systolic blood pressure (BP) > 140 or diastolic > 90 (measurement on 2 separate days) At baseline and up to 12 months The change will be estimated and tested using paired tests (Wilcoxon signed rank test or McNemar test). The difference at each interval for the two groups will be tested using Fisher's exact test for binary endpoints or Wilcoxon rank-sum test for continuous. Data transformation to fit statistical assumptions will be done as needed. Multivariable models that ...
Need for new or escalated anti-hypertensive medication At baseline and up to 12 months The change will be estimated and tested using paired tests (Wilcoxon signed rank test or McNemar test). The difference at each interval for the two groups will be tested using Fisher's exact test for binary endpoints or Wilcoxon rank-sum test for continuous. Data transformation to fit statistical assumptions will be done as needed. Multivariable models that ...
Incidence of moderate-to-severe atherosclerosis of major coronary vessels From month 0 to month 12 Defined as \> 50% luminal stenosis per the Society of Cardiac Computed Tomography. Change will be tested using paired tests (Wilcoxon signed rank test or McNemar test). Luminal stenosis will be measured on a per-vessel basis. Proportion of patients achieving \> 50% luminal stenosis of a major coronary vessel between each arm will be compared using Fisher's e...
- Secondary Outcome Measures
Name Time Method Total plaque volume From month 0 to month 12 Total plaque volume (per-patient and per-vessel basis, respectively) will be measured. Adjusted mean difference will be calculated from baseline to month 12 between arms. Multivariable adjustment will be utilized that control age and statin using logistic regression.
Pre-existing genomic alterations promoting inflammatory immunity and associated with cardiovascular disease At baseline Pre-treatment samples will be subjected to whole exome sequencing to determine alterations to the protein-coding regions of the genome, specifically those associated with clonal hematopoiesis of indeterminate potential (CHIP). The association of CHIP mutations with development of cardiovascular toxicity following therapy will be measured.
Castration rate At study days 7, 30 and 90 The cumulative probability of testosterone suppression to ≤ 50 ng/dL will be summarized using the Kaplan-Meier method. Confidence intervals will be calculated using the exponential Greenwood formulation via log-log transformation of the survival function
Sustained castration At months 6 and 12 The probability of testosterone suppression ≤ 50 ng/mL will be summarized using Kaplan-Meier. Confidence intervals will be calculated using the exponential Greenwood formulation via log-log transformation of the survival function
Testosterone recovery At day 30 and/or day 90 following completion of androgen deprivation therapy The probability of testosterone recovery \> 50 ng/mL and 200 ng/mL will be summarized using the Kaplan-Meier method. Confidence intervals will be calculated using the exponential Greenwood formulation via log-log transformation of the survival function
Trial Locations
- Locations (4)
Emory Proton Therapy Center
🇺🇸Atlanta, Georgia, United States
Winship at Emory Midtown
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States