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 \< 50 ng/dL during screening; if the patient is medically castrated, continuous dosing with luteinizing hormone-releasing hormone (LHRH) analogue must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone including post-treatment follow up period
• •No prior systemic treatment initiated for the treatment of castration resistant prostate cancer, including abiraterone acetate, enzalutamide, apalutamide, darolutamide, other novel AR or CYP17 antagonist, or docetaxel.
• •Patients receiving bone loss prevention treatment with bone-modifying agents (e.g. denosumab, zoledronic acid) must be on stable doses for at least 4 weeks prior to randomization
• •Patients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) as most recent treatment must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after washout
• •At least 4 weeks or 5 half-lives, whichever is shorter, must have elapsed from the use of any anti-cancer therapy, other than Luteinizing hormone-releasing hormone (LHRH) analog or first generation antiandrogen, prior to randomization
• •At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
• •Age \> 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