RElugolix VErsus LeUprolide Cardiac Trial

NCT05320406 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 5 other identifiers: STUDY00003654NCI-2022-00117RAD5484-21P30CA13829222YOUN21
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 4

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.

Conditions

Localized Prostate Carcinoma; Stage IIB Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Biochemically Recurrent Prostate Carcinoma; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Total Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries)

  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.

  From baseline to 12 months post-treatment initiation

Secondary Outcomes (1)

• 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

Other Outcomes (5)

• Calcified and Low-attenuation 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

• Coronary Artery Calcium Score (CACS)

  From baseline to 12 months post-treatment initiation

• Number of Participants With <30%, 30-49%, 50-69%, and >70% Maximum Coronary Vessel Stenosis at Baseline and Month 12

  From baseline to 12 months post-treatment initiation

Study Arms (3)

Arm I (radiation therapy alone)

ACTIVE COMPARATOR

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

Radiation: Radiation therapy

Arm II (radiation therapy plus leuprolide)

EXPERIMENTAL

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.

Radiation: Radiation therapy; Drug: Leuprolide

Arm III (radiation therapy plus relugolix)

EXPERIMENTAL

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.

Radiation: Radiation therapy; Drug: Relugolix

Interventions

Radiation therapy RADIATION

Undergo radiation therapy

Also known as: External beam radiation therapy, Intensity modulated radiation therapy, Proton therapy, Brachytherapy, Stereotactic body radiotherapy

Arm I (radiation therapy alone); Arm II (radiation therapy plus leuprolide); Arm III (radiation therapy plus relugolix)

Leuprolide DRUG

Given IM or SC

Also known as: Leuprolide acetate, Lupron

Arm II (radiation therapy plus leuprolide)

Relugolix DRUG

Given PO

Also known as: Orgovyx, TAK-385

Arm III (radiation therapy plus relugolix)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator
• Prostate Cancer Foundation: collaborator

Study Sites (4)

Emory Proton Therapy Center

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Related Publications (1)

• Patel SA, Yadalam AK, van Assen M, Cantu SM, Onnis C, Zheng B, Koo A, Goyal S, Liu Y, Liu C, Sebastian NT, Dhere VR, Hershatter BW, Patel PR, Chaudagar K, Stillman AE, De Cecco CN, Sanda MG, Jani AB, Mandawat A. Coronary Plaque Progression After Androgen Deprivation Therapy in Men With Prostate Cancer: A Randomized Clinical Trial. JAMA Cardiol. 2026 Feb 18:e255586. doi: 10.1001/jamacardio.2025.5586. Online ahead of print.

  PMID: 41706486 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiotherapy; Radiotherapy, Intensity-Modulated; Proton Therapy; Brachytherapy; Radiosurgery; Leuprolide; relugolix

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Heavy Ion Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr. Sagar Patel
• Organization: Emory University

sagar.patel@emory.edu

404-778-1900

Study Officials

• Sagar A Patel, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 18, 2022
• First Posted: April 11, 2022
• Study Start: June 6, 2022
• Primary Completion: January 30, 2025
• Study Completion (Estimated): October 30, 2026
• Last Updated: February 12, 2026
• Results First Posted: September 22, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)