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Active, Not Recruiting

NCT Number: NCT05320406

RElugolix VErsus LeUprolide Cardiac Trial

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Biochemically Recurrent Prostate Carcinoma Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Localized Prostate Carcinoma Male Urogenital Diseases Neoplasms Neoplasms by Site Prostatic Diseases Prostatic Neoplasms 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 Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Emory Proton Therapy Center, Atlanta, Georgia, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

radiation therapy

Radiation

Undergo radiation therapy

Other names: External beam radiation therapy, Intensity modulated radiation therapy, Proton therapy, Brachytherapy, Stereotactic body radiotherapy

Leuprolide

Drug

Given IM or SC

Other names: Leuprolide acetate, Lupron

Relugolix

Drug

Given PO

Other names: Orgovyx, TAK-385

Primary outcomes

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

    Time frame: 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 outcomes

  1. Non-calcified Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries)

    Time frame: 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.

Other outcomes

  1. Calcified and Low-attenuation Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries)

    Time frame: 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.

  2. Coronary Artery Calcium Score (CACS)

    Time frame: From baseline to 12 months post-treatment initiation

    The CACS will be measured by the Agatston score (range 0-400, with higher scores indicating more coronary artery calcium) on precontrast cardiac computed tomography anigiography (CCTA) scans by two blinded, board-certified cardiologists.

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

    Time frame: From baseline to 12 months post-treatment initiation

    Coronary computed tomographic angiography post-contrast images were used for vessel stenosis, using an artificial intelligence-informed coronary stenosis quantification tool (AI-CSQ, Roadmap Analysis, Heart flow, Mountain View CA). Stenoses regions are defined in ranges of 0-29%, 30-49%, 50-69%, and >70%. The number of participants within each treatment meeting these stenosis thresholds were quantified at baseline and month 12.

  4. Major Adverse Cardiovascular Events

    Time frame: From baseline to at least 2 years post-treatment initiation

    Incidence of myocardial infarction, need for coronary revascularization, and/or sudden cardiac death will be measured for up to 2 years following enrollment.

  5. Testosterone Kinetics

    Time frame: Baseline and month 0, 3, 6, 12

    Change in total testosterone levels (ng/dL) will be measured at baseline and month 0, 3, 6, and 12 between treatment arms. Testosterone change over time will be summarized and plotted over time for each treatment arm.

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • National Cancer Institute (NCI)
  • Prostate Cancer Foundation

Registry information

Official study title

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

Acronym: REVELUTION

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Apr 11, 2022
Registry last updated
Feb 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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