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

NCT06650579 | Recruiting Phase 3 FDA Drug

• 4 other identifiers: STUDY00007557P30CA138292NCI-2024-07761RAD6197-24
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 4

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 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.

Conditions

Recurrent Prostate Carcinoma; Stage III Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8

Keywords

node-positive prostate cancer; advanced prostate cancer; very-high-risk prostate cancer

Outcome Measures

Primary Outcomes (3)

• 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.

  At baseline and up to 12 months

• 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.

  At baseline and up to 12 months

• 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.

  From month 0 to month 12

Secondary Outcomes (5)

• Total plaque volume

  From month 0 to month 12

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

  At baseline

• Castration rate

  At study days 7, 30 and 90

• Sustained castration

  At months 6 and 12

• Testosterone recovery

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

Study Arms (2)

Arm I (leuprolide plus abiraterone acetate/prednisone)

EXPERIMENTAL

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.

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)

EXPERIMENTAL

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.

Drug: Abiraterone Acetate; Procedure: Biospecimen Collection; Procedure: Computed Tomography Angiography; Drug: Prednisone; Radiation: Radiation Therapy; Drug: Relugolix

Interventions

Computed Tomography Angiography PROCEDURE

Undergo CCTA

Also known as: CT ANGIOGRAPHY, CT Scan Angiography, CTA

Arm I (leuprolide plus abiraterone acetate/prednisone); Arm II (relugolix + abiraterone acetate/prednisone)

Bicalutamide DRUG

Given PO

Also known as: Casodex, Cassotide, Cosudex, ICI 176,334, ICI 176334, Utamide

Arm I (leuprolide plus abiraterone acetate/prednisone)

Abiraterone Acetate DRUG

Given abiraterone acetate

Also known as: BR9004, BR9004-1, CB 7630, CB-7630, CB7630, JNJ-212082, Yonsa, Zytiga

Arm I (leuprolide plus abiraterone acetate/prednisone); Arm II (relugolix + abiraterone acetate/prednisone)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (leuprolide plus abiraterone acetate/prednisone); Arm II (relugolix + abiraterone acetate/prednisone)

Leuprolide DRUG

Given IM or SC

Also known as: Leuprorelin

Arm I (leuprolide plus abiraterone acetate/prednisone)

Prednisone DRUG

Given prednisone

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Arm I (leuprolide plus abiraterone acetate/prednisone); Arm II (relugolix + abiraterone acetate/prednisone)

Radiation Therapy RADIATION

Undergo standard of care radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm I (leuprolide plus abiraterone acetate/prednisone); Arm II (relugolix + abiraterone acetate/prednisone)

Relugolix DRUG

Given PO

Also known as: 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, TAK-385, TAK385

Arm II (relugolix + abiraterone acetate/prednisone)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: collaborator
• Emory University: lead
• Pfizer: collaborator
• National Comprehensive Cancer Network: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Emory Proton Therapy Center

Atlanta, Georgia, 30308, United States

RECRUITING

Winship at Emory Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; bicalutamide; Specimen Handling; Leuprolide; Prednisone; deltacortene; prednylidene; Radiotherapy; Radiation; relugolix

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Therapeutics; Physical Phenomena

Study Officials

• Sagar A Patel, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bill Zheng, BS

CONTACT

404-686-6856; bill.zheng@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All principal investigators and co-investigators will be blinded to randomization block. All cardiac computed tomography images will be analyzed by a blinded level 3 boarded cardiac imaging expert.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 21, 2024
• Study Start: January 31, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: February 24, 2026

Record last verified: 2026-02

Locations

US (4)