REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial
February 22, 2026 updated by: Sagar Patel, Emory University
Randomized Controlled Trial of Leuprolide Plus Abiraterone Acetate (AA) Versus Relugolix Plus AA for Advanced Prostate Cancer: The REVELUTION-2 Trial
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 hormone-releasing hormone (LHRH) and luteinizing hormone (LH).
This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate tumor cells that need testosterone to grow.
Abiraterone acetate, an androgen biosynthesis inhibitor, works by decreasing the amount of certain hormones in the body.
Relugolix, a GNRH antagonist, works by decreasing the amount of testosterone produced by the body.
This may slow or stop the spread of prostate tumor cells that need testosterone to grow.
The use of hormone therapy with radiation therapy has been shown to improve survival, however, studies have suggested that the addition of hormone therapy may worsen heart (cardiac) disease and high blood pressure.
In fact, studies have shown that the most common cause of death in prostate cancer patients is due to heart disease or heart attacks.
Computed tomography (CT) scans create a series of detailed pictures of areas inside the body; the pictures are created by a computer linked to an x-ray machine.
In this study, sophisticated cardiac CT images are used to take pictures of patients' heart and coronary arteries to help assess damage to the heart.
Using cardiac CT and blood tests, this trial may help doctors determine which patients are at risk of cardiac disease when treated with combination hormone therapy, as well as the differential risk of leuprolide versus relugolix in combination with abiraterone acetate.
Study Overview
Status
Recruiting
Conditions
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:
I. Identify genomic alterations that predispose an individual to enhanced cardiovascular (CV) toxicity following hormone therapy with leuprolide or relugolix in combination with abiraterone acetate.
II. Evaluate serum testosterone kinetics during and after treatment with combination leuprolide+AA versus relugolix+AA.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive leuprolide intramuscularly (IM) or subcutaneously (SC) injection every 3 to 6 months plus oral 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. Patients may also receive bicalutamide orally (PO) once daily (QD) on days 21-30 with first injection of leuprolide at the discretion of the treating provider. All patients undergo pre-treatment and 12-month coronary computed tomography angiography (CCTA) and blood sample collection.
ARM II: Patients receive oral relugolix PO daily plus oral 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. All patients undergo pre-treatment and 12-month CCTA and blood sample collection.
After completion of study treatment, patients are followed up at 30 and 60 days for serum testosterone measurement.
Study Type
Interventional
Enrollment (Estimated)
72
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Bill Zheng, BS
- Phone Number: 404-686-6856
- Email: bill.zheng@emory.edu
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Recruiting
- Emory University Hospital/Winship Cancer Institute
-
Principal Investigator:
- Sagar A. Patel
-
Contact:
- Sagar A. Patel, MD
- Phone Number: 404-686-4835
- Email: Sagar.patel@emory.edu
-
Atlanta, Georgia, United States, 30342
- Recruiting
- Emory Saint Joseph's Hospital
-
Contact:
- Bill Zheng
- Phone Number: 404-686-6856
- Email: bill.zheng@emory.edu
-
Atlanta, Georgia, United States, 30308
- Recruiting
- Emory Proton Therapy Center
-
Contact:
- Bill Zheng
- Phone Number: 404-686-6856
- Email: bill.zheng@emory.edu
-
Atlanta, Georgia, United States, 30308
- Recruiting
- Winship at Emory Midtown
-
Contact:
- Bill Zheng
- Phone Number: 404-686-6856
- Email: bill.zheng@emory.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Arm I (leuprolide plus abiraterone acetate/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.
|
Undergo blood sample collection
Other Names:
Undergo standard of care radiation therapy
Other Names:
Given PO
Other Names:
Given IM or SC
Other Names:
Given prednisone
Other Names:
Given abiraterone acetate
Other Names:
Undergo CCTA
Other Names:
|
|
Experimental: Arm II (relugolix + abiraterone acetate/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.
|
Undergo blood sample collection
Other Names:
Undergo standard of care radiation therapy
Other Names:
Given PO
Other Names:
Given prednisone
Other Names:
Given abiraterone acetate
Other Names:
Undergo CCTA
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of ambulatory systolic blood pressure (BP) > 140 or diastolic > 90 (measurement on 2 separate days)
Time Frame: 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 control for potential confounders will be implemented using general linear and logistic regression.
|
At baseline and up to 12 months
|
|
Need for new or escalated anti-hypertensive medication
Time Frame: 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 control for potential confounders will be implemented using general linear and logistic regression.
|
At baseline and up to 12 months
|
|
Incidence of moderate-to-severe atherosclerosis of major coronary vessels
Time Frame: 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 exact test.
The percent change of maximal stenosis between the two arms will be tested using Wilcoxon signed rank test.
|
From month 0 to month 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Total plaque volume
Time Frame: 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.
|
From month 0 to month 12
|
|
Pre-existing genomic alterations promoting inflammatory immunity and associated with cardiovascular disease
Time Frame: 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.
|
At baseline
|
|
Castration rate
Time Frame: 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
|
At study days 7, 30 and 90
|
|
Sustained castration
Time Frame: 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
|
At months 6 and 12
|
|
Testosterone recovery
Time Frame: 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
|
At day 30 and/or day 90 following completion of androgen deprivation therapy
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Sagar A Patel, MD, Emory University Hospital/Winship Cancer Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 31, 2025
Primary Completion (Estimated)
July 1, 2029
Study Completion (Estimated)
July 1, 2029
Study Registration Dates
First Submitted
October 18, 2024
First Submitted That Met QC Criteria
October 18, 2024
First Posted (Actual)
October 21, 2024
Study Record Updates
Last Update Posted (Actual)
February 24, 2026
Last Update Submitted That Met QC Criteria
February 22, 2026
Last Verified
February 1, 2026
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Urogenital Diseases
- Genital Diseases
- Genital Neoplasms, Male
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms
- Genital Diseases, Male
- Prostatic Diseases
- Male Urogenital Diseases
- Prostatic Neoplasms
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Pituitary Hormone-Releasing Hormones
- Hypothalamic Hormones
- Peptide Hormones
- Neuropeptides
- Peptides
- Amino Acids, Peptides, and Proteins
- Oligopeptides
- Nerve Tissue Proteins
- Proteins
- Investigative Techniques
- Therapeutics
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Physical Phenomena
- Polycyclic Compounds
- Pregnadienes
- Pregnanes
- Steroids
- Fused-Ring Compounds
- Pregnadienediols
- Androstenes
- Androstanes
- Gonadotropin-Releasing Hormone
- Abiraterone Acetate
- Prednisone
- Leuprolide
- relugolix
- Radiotherapy
- Radiation
- Specimen Handling
- deltacortene
- prednylidene
- bicalutamide
Other Study ID Numbers
- STUDY00007557 (Other Identifier: Emory University Hospital)
- P30CA138292 (U.S. NIH Grant/Contract)
- NCI-2024-07761 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- RAD6197-24 (Other Identifier: Emory University Hospital)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.