NCT05320406

RElugolix VErsus LeUprolide Cardiac Trial

Mechanism and Predictors of Cardiotoxicity After Prostate Cancer Treatment: A Parallel Cohort and Randomized Trial Comparing Radiation Alone, Radiation Plus Leuprolide, and Radiation Plus Relugolix

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 94 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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
• Stage IIIC Prostate Cancer AJCC v8

Interventions

Type	Name	Description
RADIATION	Radiation therapy	Undergo radiation therapy
DRUG	Leuprolide	Given IM or SC
DRUG	Relugolix	Given PO

Timeline

• Start date: 2022-06-06
• Primary completion: 2025-01-30
• Completion: 2026-10-30
• First posted: 2022-04-11
• Last updated: 2026-02-12
• Results posted: 2025-09-22

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study