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

NCT ID: NCT06650579

Last Updated: 2025-02-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-31
• Study Completion Date: 2029-07-01

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: DRUG

Given abiraterone acetate

Bicalutamide

Intervention Type: DRUG

Given PO

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Computed Tomography Angiography

Intervention Type: PROCEDURE

Undergo CCTA

Leuprolide

Intervention Type: DRUG

Given IM or SC

Prednisone

Intervention Type: DRUG

Given prednisone

Radiation Therapy

Intervention Type: RADIATION

Undergo standard of care radiation therapy

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.

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: DRUG

Given abiraterone acetate

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Computed Tomography Angiography

Intervention Type: PROCEDURE

Undergo CCTA

Prednisone

Intervention Type: DRUG

Given prednisone

Radiation Therapy

Intervention Type: RADIATION

Undergo standard of care radiation therapy

Relugolix

Intervention Type: DRUG

Given PO

Interventions

Abiraterone Acetate

Given abiraterone acetate

Intervention Type: DRUG

Bicalutamide

Given PO

Intervention Type: DRUG

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Computed Tomography Angiography

Undergo CCTA

Intervention Type: PROCEDURE

Leuprolide

Given IM or SC

Intervention Type: DRUG

Prednisone

Given prednisone

Intervention Type: DRUG

Radiation Therapy

Undergo standard of care radiation therapy

Intervention Type: RADIATION

Relugolix

Given PO

Intervention Type: DRUG

Other Intervention Names

BR9004; BR9004-1; CB 7630; CB-7630; CB7630; JNJ-212082; Yonsa; Zytiga; Casodex; Cassotide; Cosudex; ICI 176,334; ICI 176334; Utamide; Biological Sample Collection; Biospecimen Collected; Specimen Collection; CT ANGIOGRAPHY; CT Scan Angiography; CTA; Leuprorelin; .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; Cancer Radiotherapy; Energy Type; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; 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

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: collaborator

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Sagar Patel

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sagar A Patel, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University Hospital/Winship Cancer Institute

Locations

Emory Proton Therapy Center

Atlanta, Georgia, United States

Site Status: RECRUITING

Winship at Emory Midtown

Atlanta, Georgia, United States

Site Status: RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status: RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Bill Zheng, BS

Role: CONTACT

bill.zheng@emory.edu

404-686-6856

Facility Contacts

Bill Zheng

Role: primary

bill.zheng@emory.edu

404-686-6856

Bill Zheng

Role: primary

bill.zheng@emory.edu

404-686-6856

Sagar A. Patel, MD

Role: primary

Sagar.patel@emory.edu

404-686-4835

Bill Zheng

Role: primary

bill.zheng@emory.edu

404-686-6856

Other Identifiers

P30CA138292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-07761

Identifier Type: REGISTRY

Identifier Source: secondary_id

STUDY00007557

Identifier Type: OTHER

Identifier Source: secondary_id

RAD6197-24

Identifier Type: OTHER

Identifier Source: secondary_id

STUDY00007557

Identifier Type: -

Identifier Source: org_study_id