RecoverPC: Relugolix vs GnRH Agonist in Quality of Life

Inclusion Criteria:

• Participants must have a histologic diagnosis of prostate adenocarcinoma.

• Participants must be eligible for treatment with 6 months of ADT with leuprolidedepot or relugolix without additional systemic therapies other than first generationandrogen receptor antagonists (eg. bicalutamide, nilutamide, flutamide).

• Participants cannot have received prior GnRH agonist or antagonist therapy.

• Patients must have testosterone level > 200 ng/mL prior to initiation of ADT.

• Age ≥18 years.

• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).

• Life expectancy of greater than 12 months

• Participants must have adequate organ and marrow function as defined below:

• leukocytes ≥3,000/mcL

• absolute neutrophil count ≥1,500/mcL

• platelets ≥100,000/mcL

• total bilirubin ≤ institutional upper limit of normal (ULN) unless known orsuspected Gilbert syndrome

• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

• creatinine ≤ institutional ULN OR

• glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 unless data existssupporting safe use at lower kidney function values, no lower than 30mL/min/1.73 m2 (see Appendix B).

• Human immunodeficiency virus (HIV)-infected participants on effectiveanti-retroviral therapy with undetectable viral load within 6 months are eligiblefor this trial.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated.

• Participants with a history of hepatitis C virus (HCV) infection must have beentreated and cured. For participants with HCV infection who are currently ontreatment, they are eligible if they have an undetectable HCV viral load.

• Participants with a prior or concurrent malignancy whose natural history ortreatment does not have the potential to interfere with the safety or efficacyassessment of the investigational regimen are eligible for this trial.

• Participants with known history or current symptoms of cardiac disease, or historyof treatment with cardiotoxic agents, should have a clinical risk assessment ofcardiac function using the New York Heart Association Functional Classification. Tobe eligible for this trial, participants should be class 2B or better.

• The effects of relugolix and leuprolide on the developing human fetus are unknown.For this reason and because GnRH agents are known to be teratogenic, women ofchild-bearing potential and men must agree to use adequate contraception (hormonalor barrier method of birth control; abstinence) prior to study entry and for theduration of study participation. Should a woman become pregnant or suspect she ispregnant while she or her partner is participating in this study, she should informher treating physician immediately. Men treated or enrolled on this protocol mustalso agree to use adequate contraception prior to the study, for the duration ofstudy participation, and 4 months after completion of relugolix or leuprolide depotadministration.

• Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

• History of major adverse cardiac event, including myocardial infarction, newcongestive heart failure (CHF) or CHF exacerbation, or stroke, within the past 6months.

• Participants who have prior or planned concurrent treatment with second generationAR targeted therapies (such as abiraterone, enzalutamide, darolutamide,apalutamide).

• Participants who are receiving any other investigational agents.

• Patients with brain metastases will be excluded from the study as intermittenthormonal therapy is not standard of care treatment for this population.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to leuprolide depot or relugolix.

• Participants with uncontrolled intercurrent illness.

• Participant is unable to swallow pills.