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

Prostate Adenocarcinoma Clinical Trial

Official title: A Comparison of Orgovyx (Relugolix) vs Eligard (Leuprolide) on Cardiovascular Function and Biomarkers During Standard of Care Combined ADT (Androgen Deprivation Therapy)-Radiation for Prostate Cancer

Status Not yet recruiting

Clinical Trial 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. Comprehensive cardiac and exercise testing before and after starting ADT

2. Completion of quality-of-life questionnaires at specific intervals during the study period

3. Provide blood samples at specific intervals during the study period to test for changes in steroid levels and certain biomarkers

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To quantify the physiologic alterations in cardiopulmonary function in men receiving 6-month relugolix verse (vs.) 6-month leuprolide with definitive radiation therapy (RT) for unfavorable intermediate risk (UIR) clinically localized prostate cancer (PCa).

II. Cardiopulmonary and cardiac measures obtained from: 1) exercise stress cardiac magnetic resonance imaging (MRI) perfusion, and 2) maximal rate of oxygen consumption (VO2), include myocardial perfusion reserve index (MPRI), contractile reserve, myocardial longitudinal relaxation time (T1) signal, longitudinal strain, circumferential strain, VO2 maximum (max), and metabolic equivalents of exercise capacity (METs).

SECONDARY OBJECTIVES:

I. To quantify the impact of 6-month relugolix vs. leuprolide with definitive RT for UIR PCa on quality of life (QoL) using Expanded Cancer Index Composite (EPIC)-26, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), European (Euro) Qol-5-Dimension 5-level (EQ-5D-5L), and Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (Short Form 8a) patient-reported outcome surveys, or similar tests.

II. To quantify the impact of 6-month relugolix vs. leuprolide on composite functional tests of strength and balance using three tests: 1) Timed Up-and-Go, 2) 10-meter walk time, and 3) grip strength.

III. To analyze body composition changes in response to 6-month relugolix vs. leuprolide by using abdominal computed tomography (CT) or magnetic resonance imaging (MRI) to quantitate abdominal/visceral fat and lean muscle mass with utilization of SliceOmatic software.

EXPLORATORY OBJECTIVES:

I. To compare changes in serum steroid profiles (panel of 17 steroid hormone metabolites, Ohio State University Comprehensive Cancer Center [OSUCCC Pharmacoanalytic Shared Resource [PhASR]) before, during and after 6-month relugolix vs. 6-month leuprolide with definitive RT for UIR PCa.

II. To compare changes in cardiometabolic biomarkers in the following three categories: 1) glycemic control parameters (fasting glucose, fasting insulin, and connecting [C]-peptide), 2) lipid profiles (total cholesterol, triglyceride, low-density lipoprotein [LDL], high-density lipoprotein [HDL], and leptin/adiponectin ratio), 3) markers of the obesity-associated low-grade chronic inflammatory state (CRP, TGF-beta, and IL-6, and novel related immunoregulators), and targeted or non- targeted metabolomics or proteomics (by OSUCCC NPASR and PSR) depending on procurement of additional funds.

III. To compare the time course of recovery for hormonal and cardiometabolic markers after completion of 6-month relugolix vs. 6-month leuprolide with definitive RT for UIR PCa.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: 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.

ARM 2: 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.

After completion of study treatment, patients are followed up at 1, 3, and 6 months. ;

Related Conditions & MeSH terms

• Prostate Adenocarcinoma
• Prostatic Neoplasms
• Stage IIB Prostate Cancer AJCC v8
• Stage IIC Prostate Cancer AJCC v8

• NCT number: NCT06330805
• Study type: Interventional
• Source: Ohio State University Comprehensive Cancer Center
• Contact: The Ohio State University Comprehensive Cancer Center
• Phone: 800-293-5066
• Email: OSUCCCClinicaltrials@osumc.edu
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2024
• Completion date: December 31, 2027