PLX3397, Radiation Therapy, and Antihormone Therapy in Treating Patients With Intermediate- or High-Risk Prostate Cancer

Inclusion Criteria: * Pathologically confirmed diagnosis of prostate adenocarcinoma * Must have confirmed viable archival prostate biopsy tissue available as per Section 8.1 (this will be collected for patients going on study after the MTD has been reached * Intermediate or high risk prostate cancer patients who are candidates for radiation therapy: * Gleason \>7 or * Clinical or pathological \> T2b disease or * PSA \> 10 ng/mL * No evidence of metastatic disease by clinical and radiological staging * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 * No standard contraindications to radiation therapy including prior significant radiation therapy, inflammatory bowel disease, irritable bowel syndrome or collagen vascular disease * Prior history of up to 8 weeks of androgen deprivation therapy defined as lutenizing-hormone releasing hormone (LHRH) or other medical castration therapy prior to registration is acceptable. This will be in addition to the 6 months of ADT on study. * Life expectancy of at least 3 months * Adequate hematologic, hepatic, and renal function as defined by: * Absolute neutrophil count ≥ 1.5 × 109/L * Hemoglobin \> 10 g/dL * Platelet count ≥ 100 × 109/L * AST and ALT ≤ upper limit of normal (ULN) * TBil and DBil ≤ ULN with an exception of patients with confirmed Gilbert's syndrome. For patients with confirmed Gilbert's syndrome, the TBil should be ≤ 1.5 × ULN * Serum creatinine ≤ 1.5 × ULN * Must have ability to take oral medication * W…