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
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
• 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.
‣ Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).
• 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.