Testing the Addition of Darolutamide to Hormonal Therapy (Androgen Deprivation Therapy [ADT]) after Surgery for Men with High-Risk Prostate Cancer, The ERADICATE Study

Inclusion Criteria

• PRE-REGISTRATION INCLUSION (STEP 0)
• Patient must be >= 18 years of age
• Patient must have undergone a radical prostatectomy (RP) completed at least 2 weeks prior to Step 0 pre-registration. Patient must also meet one of the following criteria: * For patients with a Decipher score obtained through standard of care testing outside the protocol prior to registration to Step 0: ** The Decipher score must be > 0.6. ** The patient must be registered to Step 0 no later than 24 weeks (168 days) after surgery. ** The Decipher Score assay results and report must be available for upload to Medidata Rave prior to proceeding to Step 1 Randomization * For patients without a previous Decipher score performed through standard of care testing outside the protocol prior to registration to Step 0 ** The patient must be registered to Step 0 no later than 19 weeks (133 days) after surgery to allow time to have tissue submitted and tested before proceeding to Step 1 randomization. ** The patient must have a Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score >= 3. The CAPRA-S score is calculated by assigning points for PSA in ng/mL, Gleason score, surgical margin status, seminal vesicle invasion, and extra-capsular extension. Lymph node involvement will serve as an exclusion criteria and will not count towards CAPRA-S inclusion score. ** Tumor tissue specimen from radical prostatectomy must be available and ready to be shipped within 20 weeks post-surgery. * NOTE: Every effort should be made to submit adequate tumor tissue specimen to Decipher Biosciences for testing immediately. Decipher Biosciences will notify submitting institution of Decipher score results within 21 days of receipt of adequate tumor tissue specimens. Failure to submit adequate tissue will result in request for additional tissue and delays in testing and reporting
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• INCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)
• Patient must be randomized to Step 1 a minimum of 6 weeks and a maximum of 24 weeks (168 days) from radical prostatectomy (RP)
• For patients who did not have a Decipher score obtained through standard of care testing outside of the protocol prior to registration to Step 0, the Decipher score is > 0.6 assessed from the prostatectomy specimen submitted
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0- 2
• Patients with a prior or concurrent malignancy within 5 years of Step 1 randomization, whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• 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
• Patient must be able to take oral medications
• Patient must have a PSA < 0.2 ng/mL obtained within 2 weeks prior to Step 1 randomization
• Patient must not have pre or post-operative radiographic evidence of cancer recurrence or metastasis by abdominal and pelvic imaging (computed tomography [CT] abdomen/pelvis, whole body magnetic resonance imaging [MRI], MRI abdomen/pelvis, or equivalent, AND bone scan) within 24 weeks (168 days) prior to Step 1 randomization. If pre-operative risk does not support a need for CT abdomen/pelvis and/or bone scan imaging, the lack of baseline imaging due to low risk disease should be documented. * NOTE: A post-operative Decipher Score of > 0.6 indicates an increased risk of metastatic disease and a bone scan or CT scan is required prior to Step 1 randomization
• Due to the potential harm through seminal transfer to an unborn fetus with the treatment regimens being used, sexually active patients must not expect to father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 28 days after the last dose of protocol treatment
• Leukocytes >= 3,000/mcL (obtained within 4 weeks prior to Step 1 randomization)
• Absolute neutrophil count (ANC) >= 1,000/mcL (obtained within 4 weeks prior to Step 1 randomization)
• Platelets >= 75,000/mcL (obtained within 4 weeks prior to Step 1 randomization)
• Hemoglobin (Hgb) > 8 g/dL (obtained within 4 weeks prior to Step 1 randomization)
• Total bilirubin =< institutional upper limit of normal (ULN) (or =< 3 x ULN for patients with known Gilbert’s disease) (obtained within 4 weeks prior to Step 1 randomization)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks prior to Step 1 randomization)
• Glomerular filtration rate (GFR) > 30 mL/min/1.73 m^2 estimated by Modification of Diet in Renal Disease (MDRD) formula (obtained within 4 weeks prior to Step 1 randomization)

Exclusion Criteria

• PRE-REGISTRATION EXCLUSION (STEP 0)
• Patient must not have any previous treatment with androgen deprivation therapy (ADT), chemotherapy, or other physician prescribed systemic therapy for treatment of their prostate cancer * NOTE: Prior treatment with bicalutamide is permitted
• EXCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)
• Patient must not have pathologic evidence of pelvic lymph node involvement
• Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements