Apalutamide With or Without Stereotactic Body Radiation in Treating Castration-Resistant Prostate Cancer

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Progressive, castration-resistant prostate cancer demonstrated during continuous antiandrogen therapy (ADT), defined as 3 PSA rises at least 1 week apart, with a minimum PSA > .05 ng/mL obtained during screening.
• At least one but no more than 5 discrete PSMA-avid radiation fields on baseline PSMA-PET scan; all PSMA-avid lesions in radiation fields must be amenable to SBRT in judgment of treating radiation oncologist; there are no restrictions on site of lesion/radiation fields (e.g. bone, lymph node, prostate, visceral). Equivocal lesions/radiation fields on PSMA PET scan that are not definitive for metastasis will not count towards the limit of 5 radiation fields and will not undergo SBRT
• Surgically or medically castrated, with testosterone levels of 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
• Resolution of all acute toxic effects of prior therapy or surgical procedure to grade 1 or baseline prior to randomization
• Serum aspartate transaminase (AST) ((serum glutamic oxaloacetic transaminase (SGOT])) and serum alanine transaminase (ALT) (( serum glutamic pyruvic transaminase (SGPT)) ≤ 2.5 x upper limit of normal (ULN)
• Total serum bilirubin ≤ 1.5 x ULN; in subjects with known or suspected Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, direct bilirubin is ≤ 1.5 x ULN
• Glomerular filtration rate ≥ 45 ml/min based on Cockcroft-Gault equation
• Absolute neutrophil count (ANC) ≥ 1500/microliter
• Platelets ≥ 75, 000/microliter without transfusion and/or growth factors in the 3 months prior to randomization
• Hemoglobin ≥ 9.0 g/dL without transfusion and/or growth factors in the 3 months prior to randomization
• Serum albumin ≥ 3.0 g/dL
• Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to randomization
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory and radiographic assessments, and other study procedures, including ability to swallow study drug tablets and long-term follow-up
• Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria

• Presence of visceral lesions (e.g. lung, liver) detectable on baseline imaging or bone lesions requiring focal radiation treatment at the time of study entry
• History of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system (CNS) or meningeal disease which may require treatment with surgery or radiation therapy
• Concurrent therapy with any of the following (all must have been discontinued or substituted for at least 1 week prior to randomization, except for medications known to lower seizure threshold which must be discontinued or substituted at least 4 weeks prior to randomization)
• Medications known to lower the seizure threshold
• Herbal (e.g., saw palmetto) and non-herbal (e.g., pomegranate) products that may decrease PSA levels
• Systemic (oral/intravenous (IV)/intramuscular (IM)) corticosteroids; patients on chronic stable dose of steroids at an equivalent dose of prednisone ≤ 10 mg daily may be permitted to enroll at the discretion of principal investigator
• Any other experimental treatment on another clinical trial
• Any of the following within 6 months prior to randomization: Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromb