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

Last updated: February 20, 2025
Sponsor: Emory University
Overall Status: Active - Recruiting

Phase

3

Condition

Urologic Cancer

Prostate Disorders

Prostate Cancer, Early, Recurrent

Treatment

Biospecimen Collection

Prednisone

Abiraterone Acetate

Clinical Study ID

NCT06650579
STUDY00007557
P30CA138292
RAD6197-24
NCI-2024-07761
STUDY00007557
  • Ages > 18
  • Male

Study 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.

Eligibility Criteria

Inclusion

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) withor without brachytherapy

  • Plan to undergo up to 24 months of combination androgen deprivation therapy (ADT)plus AA and prednisone

Exclusion

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 Design

Total Participants: 72
Treatment Group(s): 8
Primary Treatment: Biospecimen Collection
Phase: 3
Study Start date:
January 31, 2025
Estimated Completion Date:
July 01, 2029

Study 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.

Connect with a study center

  • Emory Proton Therapy Center

    Atlanta, Georgia 30308
    United States

    Active - Recruiting

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia 30342
    United States

    Active - Recruiting

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

  • Winship at Emory Midtown

    Atlanta, Georgia 30308
    United States

    Active - Recruiting

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