RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

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

Quick Facts

Study Start:2024-08-12

Study Completion:2027-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06330805

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * Clinically negative lymph nodes (N0) as established by conventional imaging (pelvic +/- abdominal CT or MRI), within 120 days prior to registration (lymph nodes equivocal or questionable by imaging are eligible if the nodes are ≤ 1.0 cm in short axis and/or if biopsy is negative) * Prostate specific membrane antigen (PSMA) or fluciclovine PET negative for nodal or distant metastatic disease is an acceptable substitute for the above bone and pelvic imaging * Age ≥ 18 * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 120 days prior to registration. * Non-castrate testosterone level (\> 50 ng/dL) within 120 days prior to registration. * Absolute neutrophil ≥ 1,000 cells/mm\^3 (within 120 days prior to registration) * Hemoglobin ≥ 10 g/dL (within 120 days prior to registration) * Platelet count ≥ 100,000 cells/mm\^3 (within 120 days prior to registration) * Creatinine clearance (CrCl) ≥ 30 mL/min estimated by Cockcroft-Gault Equation (within 120 days prior to registration) * For African American patients, CrCl ≥ 30 mL/min is estimated by the alternative formula that takes race into account * Total bilirubin: 1.5 ≤ institutional upper limit of normal (ULN) (within 120 days prior to registration) * Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 2.5 × institutional ULN (within 120 days prior to registration) * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: HIV testing is not required for eligibility for this protocol. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. * For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information.	* 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. * Significant uncontrolled gastrointestinal (e.g. Crohn's disease, ulcerative colitis) or metabolic disease (e.g. diabetes, hyperlipidemia). * Active inflammatory or immune-related disease treated with steroids or immunosuppressive agents. * Inability to swallow oral pills. * High risk features, which includes any of the following: * Gleason 8-10 \[ISUP grade group 4-5\] * PSA\>20 * cT3-4 by digital exam OR gross extra-prostatic extension on imaging \[indeterminate MRI evidence will not count and the patient will be eligible\]

Inclusion Criteria

Exclusion Criteria

* 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
* Clinically negative lymph nodes (N0) as established by conventional imaging (pelvic +/- abdominal CT or MRI), within 120 days prior to registration (lymph nodes equivocal or questionable by imaging are eligible if the nodes are ≤ 1.0 cm in short axis and/or if biopsy is negative)
* Prostate specific membrane antigen (PSMA) or fluciclovine PET negative for nodal or distant metastatic disease is an acceptable substitute for the above bone and pelvic imaging
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 120 days prior to registration.
* Non-castrate testosterone level (\> 50 ng/dL) within 120 days prior to registration.
* Absolute neutrophil ≥ 1,000 cells/mm\^3 (within 120 days prior to registration)
* Hemoglobin ≥ 10 g/dL (within 120 days prior to registration)
* Platelet count ≥ 100,000 cells/mm\^3 (within 120 days prior to registration)
* Creatinine clearance (CrCl) ≥ 30 mL/min estimated by Cockcroft-Gault Equation (within 120 days prior to registration)
* For African American patients, CrCl ≥ 30 mL/min is estimated by the alternative formula that takes race into account
* Total bilirubin: 1.5 ≤ institutional upper limit of normal (ULN) (within 120 days prior to registration)
* Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 2.5 × institutional ULN (within 120 days prior to registration)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: HIV testing is not required for eligibility for this protocol.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy.
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information.

* 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.
* Significant uncontrolled gastrointestinal (e.g. Crohn's disease, ulcerative colitis) or metabolic disease (e.g. diabetes, hyperlipidemia).
* Active inflammatory or immune-related disease treated with steroids or immunosuppressive agents.
* Inability to swallow oral pills.
* High risk features, which includes any of the following:
* Gleason 8-10 \[ISUP grade group 4-5\]
* PSA\>20
* cT3-4 by digital exam OR gross extra-prostatic extension on imaging \[indeterminate MRI evidence will not count and the patient will be eligible\]

Contacts and Locations

Study Contact

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066

OSUCCCClinicaltrials@osumc.edu

Principal Investigator

Shang-Jui Wang, MD, PhD

PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Study Locations (Sites)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

Collaborators and Investigators

Sponsor: Ohio State University Comprehensive Cancer Center

Shang-Jui Wang, MD, PhD, PRINCIPAL_INVESTIGATOR, Ohio State University Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-08-12

Study Completion Date2027-12-31

Study Record Updates

Study Start Date2024-08-12

Study Completion Date2027-12-31

Terms related to this study

Additional Relevant MeSH Terms

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