RElugolix VErsus LeUprolide Cardiac Trial

NCT ID: NCT05320406

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-06
• Study Completion Date: 2025-12-30

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.

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

Study Design

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

Study Groups

Arm I (radiation therapy alone)

Patients undergo definitive radiation therapy alone (IMRT, SBRT, proton therapy, brachytherapy) in the absence of disease progression or unacceptable toxicity.

Group Type: ACTIVE_COMPARATOR

Radiation therapy

Intervention Type: RADIATION

Undergo radiation therapy

Arm II (radiation therapy plus 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.

Group Type: EXPERIMENTAL

Radiation therapy

Intervention Type: RADIATION

Undergo radiation therapy

Leuprolide

Intervention Type: DRUG

Given IM or SC

Arm III (radiation therapy plus 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.

Group Type: EXPERIMENTAL

Radiation therapy

Intervention Type: RADIATION

Undergo radiation therapy

Relugolix

Intervention Type: DRUG

Given PO

Interventions

Radiation therapy

Undergo radiation therapy

Intervention Type: RADIATION

Leuprolide

Given IM or SC

Intervention Type: DRUG

Relugolix

Given PO

Intervention Type: DRUG

Other Intervention Names

External beam radiation therapy; Intensity modulated radiation therapy; Proton therapy; Brachytherapy; Stereotactic body radiotherapy; Leuprolide acetate; Lupron; Orgovyx; TAK-385

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 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

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Prostate Cancer Foundation

OTHER

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

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

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2022-00117

Identifier Type: REGISTRY

Identifier Source: secondary_id

STUDY00003654

Identifier Type: -

Identifier Source: secondary_id

RAD5484-21

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA138292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22YOUN21

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

STUDY00003654

Identifier Type: -

Identifier Source: org_study_id