Relugolix and Enzalutamide in Combination With Radiation Therapy for the Treatment of Very High Risk Prostate Cancer, OPTIMAL Trial

Inclusion Criteria

• •Patients must have histologically confirmed prostate adenocarcinoma consistent with NCCN very-high-risk (VHR) prostate cancer defined with at least one of the following:
• •* cT3b-cT4 (American Joint Committee on Cancer \[AJCC\] 9.0)
• •* \> 4 cores with grade group 4 or 5 prostate cancer
• •* Primary gleason pattern 5
• •* 2 or 3 NCCN high-risk features.
• •Patients with involved pelvic lymph nodes below the common iliac bifurcation will be allowed as long as the criteria for VHR (very-high risk) are met
• •Patients must be age ≥ 18 years
• •Patients must have testosterone \> 50 ng/dL within 90 days prior to registration
• •* Note: Prior androgen deprivation (gonadotrophin releasing hormone \[GnRH\] analog and/or non-steroidal antiandrogen) therapy is allowed provided that it is less than 60 days of prior total duration and that serum testosterone concentration must be ≥ 50 ng/dL prior to enrollment; 5-alpha reductase inhibitors will not impact eligibility, but must be discontinued prior to starting protocol treatment
• •Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• •Leukocytes (white blood cells \[WBC\]) ≥ 2,500/mcL
• •Absolute neutrophil count (ANC) ≥ 1,500/mcL
• •Hemoglobin (Hgb) ≥ 8 g/dL
• •Platelets (PLT) ≥ 80,000/mcL
• •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) ≤ 3 x institutional upper limit of normal (ULN)
• •Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional ULN
• •Creatinine ≤ institutional ULN
• •Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m\^2
• •* Estimated GFR (eGFR) is estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation
• •For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 3 months prior to registration with a CD4 count of ≥ 200 cells/μL. Note also that HIV testing is not required for eligibility for this protocol as it is self-reported
• •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. To be eligible for this trial, patients should be better than class III
• •Patients must not have contraindications to magnetic resonance (MR) imaging and be able to lie flat and still for approximately 30-40 minutes and be able to tolerate PET/CT imaging and radiation therapy treatment planning and delivery
• •Patients with female partners of reproductive potential must agree to use effective contraception during treatment with and for 3 months after the last dose. Male patients must use a condom during sex with a pregnant woman
• •Patients must have the ability to understand and the willingness to sign a written informed consent document and comply with the study requirements