Clinical trial NCT06650579: REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial
Official title: Randomized Controlled Trial of Leuprolide Plus Abiraterone Acetate (AA) Versus Relugolix Plus AA for Advanced Prostate Cancer: The REVELUTION-2 Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Sumitomo Pharma America, Inc.
name: National Comprehensive Cancer Network
name: National Cancer Institute (NCI)
First posted: 2024-10-21
Enrollment: 72
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of ambulatory systolic blood pressure (BP) > 140 or diastolic > 90 (measurement on 2 separate days)
timeFrame: At baseline and up to 12 months
measure: Need for new or escalated anti-hypertensive medication
timeFrame: At baseline and up to 12 months
measure: Incidence of moderate-to-severe atherosclerosis of major coronary vessels
timeFrame: From month 0 to month 12
Secondary outcomes:
measure: Total plaque volume
timeFrame: From month 0 to month 12
measure: Pre-existing genomic alterations promoting inflammatory immunity and associated with cardiovascular disease
timeFrame: At baseline
measure: Castration rate
timeFrame: At study days 7, 30 and 90
measure: Sustained castration
timeFrame: At months 6 and 12
measure: Testosterone recovery
timeFrame: At day 30 and/or day 90 following completion of androgen deprivation therapy
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Proton Therapy Center
state: Georgia
city: Atlanta
country: United States
facility: Winship at Emory Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
Study officials:
affiliation: Emory University Hospital/Winship Cancer Institute
name: Sagar A Patel, MD
role: PRINCIPAL_INVESTIGATOR
References: