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Recurrent Prostate CarcinomaPhase 3NCT06650579

REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial

A Phase 3 study testing Abiraterone Acetate, Bicalutamide and Biospecimen Collection in people with Recurrent Prostate Carcinoma and Stage III Prostate Cancer AJCC v8, run by Emory University at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Abiraterone Acetate, Bicalutamide and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
4 sitesUnited States
Study dates
31 Jan 2025to 1 Jul 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Bill Zheng, BS contact

404-686-6856

bill.zheng@emory.edu

United States4 sites, 4 recruiting

  • Emory Proton Therapy Center

    Atlanta, Georgia, 30308

    Bill Zheng, 404-686-6856, bill.zheng@emory.edu

    Recruiting

  • Winship at Emory Midtown

    Atlanta, Georgia, 30308

    Bill Zheng, 404-686-6856, bill.zheng@emory.edu

    Recruiting

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

    Sagar A. Patel, MD, 404-686-4835, Sagar.patel@emory.edu

    Sagar A. Patel

    Recruiting

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

    Bill Zheng, 404-686-6856, bill.zheng@emory.edu

    Recruiting

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

Being tested
Abiraterone Acetate, Bicalutamide, Biospecimen Collection, Computed Tomography Angiography, Leuprolide
Keywords
node-positive prostate cancer, advanced prostate cancer, very-high-risk prostate cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Abiraterone AcetateDrug

    Also called BR9004, BR9004-1, CB 7630, CB-7630

    Given abiraterone acetate

  • BicalutamideDrug

    Also called Casodex, Cassotide, Cosudex, ICI 176,334

    Given PO

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Computed Tomography AngiographyProcedure or surgery

    Also called CT ANGIOGRAPHY, CT Scan Angiography, CTA

    Undergo CCTA

  • LeuprolideDrug

    Also called Leuprorelin

    Given IM or SC

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given prednisone

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo standard of care radiation therapy

  • RelugolixDrug

    Also called N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea, Orgovyx, Relumina, TAK 385

    Given PO

Study groups in NCT06650579
Study groupRoleWhat they receive
Arm I (leuprolide plus abiraterone acetate/prednisone)ExperimentalPatients 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.
Receives: Drug: Abiraterone Acetate; Drug: Bicalutamide; Procedure: Biospecimen Collection; Procedure: Computed Tomography Angiography; Drug: Leuprolide; Drug: Prednisone; Radiation: Radiation Therapy
Arm II (relugolix + abiraterone acetate/prednisone)ExperimentalPatients 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.
Receives: Drug: Abiraterone Acetate; Procedure: Biospecimen Collection; Procedure: Computed Tomography Angiography; Drug: Prednisone; Radiation: Radiation Therapy; Drug: Relugolix

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of ambulatory systolic blood pressure (BP) > 140 or diastolic > 90 (measurement on 2 separate days)

    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.

    Measured: At baseline and up to 12 months

  2. Need for new or escalated anti-hypertensive medication

    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.

    Measured: At baseline and up to 12 months

  3. Incidence of moderate-to-severe atherosclerosis of major coronary vessels

    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.

    Measured: From month 0 to month 12

Secondary outcomes (5)

  1. Total plaque volume

    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.

    Measured: From month 0 to month 12

  2. Pre-existing genomic alterations promoting inflammatory immunity and associated with cardiovascular disease

    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.

    Measured: At baseline

  3. Castration rate

    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

    Measured: At study days 7, 30 and 90

  4. Sustained castration

    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

    Measured: At months 6 and 12

  5. Testosterone recovery

    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

    Measured: At day 30 and/or day 90 following completion of androgen deprivation therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2024
  2. Study start31 Jan 2025
  3. Primary completion1 Jul 2029 (estimated)
  4. Study completion1 Jul 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
72 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06650579
Sponsor's protocol ID
STUDY00007557
Other IDs
P30CA138292, NCI-2024-07761, STUDY00007557, RAD6197-24
Status last verified
Feb 2026
First submitted
18 Oct 2024
Last updated
24 Feb 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Abiraterone Acetate, Bicalutamide and Biospecimen Collection in people with Recurrent Prostate Carcinoma and Stage III Prostate Cancer AJCC v8, run by Emory University at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Bill Zheng, BS (404-686-6856, bill.zheng@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06650579.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.

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