Optimizing Treatment and Advanced Multi-Imaging Response Evaluation for Very-High-Risk Prostate Cancer (OPTIMAL) - a Phase II Single Arm Study
This phase II trial tests how well relugolix and enzalutamide, in combination with radiation therapy, works in treating patients with very high risk prostate cancer. Relugolix is a form of androgen deprivation therapy. It prevents the release of testosterone, a hormone required to sustain prostate growth. Reducing testosterone levels may inhibit the proliferation of prostate tumor cells that need testosterone to grow. Enzalutamide is an androgen receptor signaling inhibitor. It inhibits the activity of prostate tumor cell receptors, which may reduce proliferation of prostate tumor cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Adding relugolix and enzalutamide to radiation therapy may be more effective at treating patients with very high risk prostate cancer than giving any of these treatments alone.
• 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