Effects of Relugolix vs Leuprolide on Cardiac Function in Patients With Prostate Cancer

NCT06330805 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-23069NCI-2024-00705
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial compares the effect of relugolix to leuprolide on cardiac function and performance in patients with prostate cancer. Androgen deprivation therapy (ADT) has been a key component for the treatment of advanced prostate cancer for decades. The term androgen deprivation therapy means lowering a man's testosterone. Long-term studies show that ADT may contribute to a detriment to cardiac health and predisposes men to developing cardiac diseases. Recent studies suggest that men taking relugolix for treatment of prostate cancer may have a lower risk of developing cardiovascular problems, but more studies are needed to understand this observation, and there are currently no studies reporting the direct impact of ADT (relugolix, versus the more-commonly used leuprolide) on cardiac function and outcomes. Participants will receive definitive radiotherapy for unfavorable intermediate risk prostate cancer and 6-month ADT (either relugolix or leuprolide). In addition, participants will undergo the following:

1. 1.Comprehensive cardiac and exercise testing before and after starting ADT
2. 2.Completion of quality-of-life questionnaires at specific intervals during the study period
3. 3.Provide blood samples at specific intervals during the study period to test for changes in steroid levels and certain biomarkers

Conditions

Prostate Adenocarcinoma; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Physiologic alterations in cardiopulmonary function - Myocardial perfusion

  We will measure the difference in myocardial perfusion with exercise stress-rest cardiac MRI before and after ADT (leuprolide vs. relugolix).

  Up to 6 months

• Physiologic alterations in cardiopulmonary function - Maximal rate of oxygen consumption

  We will measure the difference in VO2 Max before and after ADT (leuprolide vs. relugolix).

  Up to 6 months

Secondary Outcomes (8)

• Quality of life using EPIC-26

  Up to 6 months

• Quality of life using EORTC QLQ-C30

  Up to 6 months

• Quality of life using European (Euro) Qol-5-Dimension 5-level (EQ-5D-5L)

  Up to 6 months

• Quality of life using PROMIS

  Up to 6 months

• Functional tests of strength and balance using Timed Up-and-Go

  Up to 6 months

Study Arms (2)

Arm 1 (leuprolide)

EXPERIMENTAL

Patients receive definitive therapy for prostate cancer with ADT (leuprolide via injection once every 3 months, for a total of 6 months) in the absence of disease progression or unacceptable toxicity and definitive radiotherapy within 90 days of starting ADT. Patients receive gadolinium-based contrast intravenously (IV) and undergo exercise-stress cardiac MRI perfusion and comprehensive exercise physiology testing before starting ADT and at 6 months after starting ADT. Patients also undergo blood and urine sample collection throughout the study, as well as completion of quality-of-life questionnaires.

Procedure: Biospecimen Collection; Other: Contrast Agent; Drug: Leuprolide; Procedure: Magnetic Resonance Imaging; Other: Physical Performance Testing

Arm 2 (relugolix)

EXPERIMENTAL

Patients receive definitive therapy for prostate cancer with ADT (relugolix orally once daily for a total of 6 months) in the absence of disease progression or unacceptable toxicity and definitive radiotherapy within 90 days of starting ADT. Patients receive gadolinium-based contrast intravenously (IV) and undergo exercise-stress cardiac MRI perfusion and comprehensive exercise physiology testing before starting ADT and at 6 months after starting ADT. Patients also undergo blood and urine sample collection throughout the study, as well as completion of quality-of-life questionnaires.

Procedure: Biospecimen Collection; Other: Contrast Agent; Procedure: Magnetic Resonance Imaging; Other: Physical Performance Testing; Drug: Relugolix

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 1 (leuprolide); Arm 2 (relugolix)

Contrast Agent OTHER

Given IV

Also known as: Contrast, Contrast Drugs, contrast material, Contrast Medium

Arm 1 (leuprolide); Arm 2 (relugolix)

Leuprolide DRUG

Given injection

Also known as: Leuprorelin

Arm 1 (leuprolide)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm 1 (leuprolide); Arm 2 (relugolix)

Physical Performance Testing OTHER

Undergo functional fitness tests

Also known as: Physical Fitness Testing, Physical Function Testing

Arm 1 (leuprolide); Arm 2 (relugolix)

Relugolix DRUG

Given PO

Also known as: N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea, Orgovyx, Relumina, TAK 385, TAK-385

Arm 2 (relugolix)

Eligibility Criteria

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

You may qualify if:

• Pathologically proven diagnosis of adenocarcinoma of the prostate within 270 days prior to registration.
• Unfavorable intermediate risk prostate cancer, defined as having ALL the following bulleted criteria:
• Has at least one intermediate risk factor (IRF):
• Prostate-specific antigen (PSA) 10-20 ng/mL
• Clinical stage tumor (T)2b-c (digital rectal exam \[DRE\] and/or imaging) by American Joint Committee on Cancer (AJCC) 8th edition
• Gleason Score 7 (Gleason 3+4 or 4+3 \[International Society of Urological Pathology \[ISUP\] grade group 2-3\])
• Has one or more of the following "unfavorable" intermediate-risk designators:
• \> 1 IRF
• Gleason 4+3=7 (ISUP grade group 3)
• ≥ 50% of biopsy cores positive
• Biopsies may include "sextant" sampling of right/left regions of the prostate, often labeled base, mid-gland and apex. All such "sextant" biopsy cores should be counted. Men may also undergo "targeted" sampling of prostate lesions (guided by MRI, ultrasound or other approaches). A targeted lesion that is biopsied more than once and demonstrates cancer (regardless of number of targeted cores involved) should count as a single additional positive core sampled and positive. In cases of uncertainty, count the biopsy sampling as sextant core(s).
• Absence of high-risk features
• Appropriate stage based on the following diagnostic workup:
• History/physical examination within 120 days prior to registration
• Negative bone imaging (M0) with Tc-99m bone scan or fluciclovine (18F) sodium fluoride (NaF) positron emission tomography (PET) within 120 days prior to registration

You may not qualify if:

• Previous radical surgery (prostatectomy) or any form of curative-intent ablation whether focal or whole-gland (e.g., cryosurgery, High-intensity focused ultrasound (HIFU), laser thermal ablation, etc.) for prostate cancer.
• Definitive clinical or radiologic evidence of metastatic disease (M1).
• Prior invasive malignancy (except non-melanomatous skin cancer) or hematologic malignancy unless disease free for a minimum of 3 years.
• Prior radiotherapy to the prostate/pelvis region that would result in overlap of radiation therapy fields.
• Previous bilateral orchiectomy.
• Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate). ADT started prior to study registration is not allowed.
• Prior use of 5-alpha-reductase inhibitors is allowed; however, it must be stopped ≥ 30 days prior to the pre-registration PSA measure for determining enrollment eligibility.
• Prior testosterone replacement therapy is allowed; however, any replacement therapy must be stopped for at least 1 year prior to registration.
• Severe, active co-morbidity defined as follows:
• Current/uncontrolled angina or arrhythmias
• New York Heart Association Functional Classification II-IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
• History of any condition that in the opinion of the investigator, would preclude participation in this study
• Patients with significant obstructive urinary symptoms that are suspected to be secondary to prostate cancer and/or benign prostatic hypertrophy.
• Disabilities that prevent performing moderate intensity exercise test with exercise (treadmill) stress test and muscle function tests (walking/gait assessments and grip strength).
• Patients unable to tolerate MRI (e.g. claustrophobia), has contraindications to MRI (e.g. metals and implants incompatible with MRI), body habitus preventing MRI scanning, or allergy to gadolinium-based contrast.

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Pfizer: collaborator
• Sumitomo Pharma America, Inc.: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Specimen Handling; Contrast Media; Leuprolide; Magnetic Resonance Spectroscopy; Exercise Test; 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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; 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; Spectrum Analysis; Chemistry Techniques, Analytical; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry

Study Officials

• Shang-Jui Wang, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 2, 2024
• First Posted: March 26, 2024
• Study Start: August 12, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)