RElugolix VErsus LeUprolide Cardiac Trial

Phase 2

Active, not recruiting

• Conditions: Biochemically Recurrent Prostate Carcinoma; Localized Prostate Carcinoma; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8
• Interventions: Radiation: Radiation therapy; Drug: Leuprolide; Drug: Relugolix

• Registration Number: NCT05320406
• Lead Sponsor: Emory University

Brief Summary

This clinical trial investigates the impact of prostate cancer treatment, specifically androgen deprivation therapy (ADT), on the heart and coronary vessels among men with localized, non-metastatic prostate cancer undergoing definitive radiation therapy and concomitant ADT. Recently, cardiovascular toxicity from hormone therapy that is routinely used for prostate cancer (e.g. leuprolide) has emerged as a concern, yet studies identifying who is at risk and the mechanism of cardiac damage are lacking. Additionally, a new hormone therapy drug, relugolix, has recently been Food and Drug Administration (FDA)-approved and may reduce toxicity to the heart. This trial intends to investigate the mechanism of cardiovascular toxicity from ADT, investigate the mechanism by which relugolix reduces cardiovascular toxicity, and identify predictive biomarkers to improve individualized risk-assessment for cardiovascular toxicity from ADT.

Detailed Description

PRIMARY OBJECTIVES:

I. Identify and compare the association of gonadotrophin releasing hormone (GNRH)-agonist leuprolide versus GNRH-antagonist relugolix with coronary atherosclerosis and progression in men with prostate cancer.

II. Determine the relationship between leuprolide versus relugolix with downstream immune effector response that is implicated in atherosclerosis.

II. Determine how pre-existing genomic alterations associated with proinflammatory immunity impact development of CV toxicity following GNRH-agonist (GNRHa) versus relugolix.

III. Identify imaging biomarkers associated with increased risk of CV toxicity from ADT

OUTLINE: Patients undergoing radiation therapy alone as part of their standard treatment are assigned to Arm I. Patients undergoing radiation therapy and ADT as part of their standard treatment are randomized to Arm II or Arm III.

ARM I: Patients undergo definitive radiation therapy in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo radiation therapy as in Arm I and receive leuprolide subcutaneously (SC) or intramuscularly (IM) every 3 or 6 months. Treatment continues for 6 to 24 months (depending on cancer risk) in the absence of disease progression or unacceptable toxicity.

ARM III: Patients undergo radiation therapy as in Arm I and receive relugolix orally (PO) once daily (QD) for 6 to 24 months (depending on risk) in the absence of disease progression or unacceptable toxicity.

Study Timeline

• Study First Submitted: 2022-03-18
• Study First Submitted QC: 2022-04-01
• Study First Posted: 2022-04-11
• Study Start: 2022-06-06
• Primary Completion: 2025-01-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-30
• Last Update Posted: 2025-06-03
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 94

Inclusion Criteria

• Men >= 18 years old
• Non-metastatic prostate cancer
• Non-metastatic, biochemically recurrent prostate cancer
• Plan to undergo curative-intent pelvic radiation therapy with or without ADT

Exclusion Criteria

• Metastatic prostate cancer requiring > 24 months of ADT
• Prior exposure to androgen deprivation therapy
• Prior exposure to chemotherapy or immunotherapy
• History of cardiac bypass surgery or percutaneous coronary intervention

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (radiation therapy alone)	Radiation therapy	Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity.
Arm III (radiation therapy plus relugolix)	Radiation therapy	Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.
Arm II (radiation therapy plus leuprolide)	Radiation therapy	Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.
Arm II (radiation therapy plus leuprolide)	Leuprolide	Patients undergo radiation therapy as in Arm I and receive leuprolide SC or IM every 3 or 6 months. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.
Arm III (radiation therapy plus relugolix)	Relugolix	Patients undergo radiation therapy as in Arm I and receive relugolix PO QD. Treatment continues for 6 to 12 months (depending on risk) in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Total coronary plaque volume in major coronary arteries (i.e. left anterior descending, left circumflex, right major coronary arteries)	From baseline to 12 months post-treatment initiation	Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments.

Secondary Outcome Measures

Name	Time	Method
Non-calcified coronary plaque volume in major coronary arteries (i.e. left anterior descending, left circumflex, right major coronary arteries)	From baseline to 12 months post-treatment initiation	Using cardiac computed tomography angiography (CCTA), total coronary plaque volume will be determined using an artificial intelligence-enabled quantitative coronary plaque analysis (AI-QCPA) through a commercially available and validated software service (HeartFlow, Inc). Each coronary artery (right coronary, left main, left anterior descending, and left circumflex) will be scored, and plaque volumes were summed over all segments.

Trial Locations

Locations (4)

Emory Proton Therapy Center; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States

Emory University/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Emory Saint Joseph's Hospital; 🇺🇸 Atlanta, Georgia, United States