Enzalutamide and Decitabine in Treating Patients With Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria: * Histological or cytological documentation of diagnosis of prostate cancer, all histological sub-types included. * Documented progressive metastatic castrate resistant prostate cancer (mCRPC) based on at least one of the following criteria: * PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1week interval and a minimum PSA of 2 ng/mL * Soft-tissue progression defined as an increase \>= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions * Progression of bone disease (evaluable disease) or (new bone lesion\[s\]) by bone scan * If on an anti-androgen, must have documented progression 6 weeks after stopping anti-androgen therapy * Willing to undergo a biopsy, if readily available biopsy site present, i.e., nodal or visceral metastasis (if adequate formalin-fixed, paraffin-embedded (FFPE) archival mCRPC samples are not available (or biopsy was taken longer than 6 months from start of study treatment), a fresh pre-treatment mCRPC biopsy needs to be obtained) * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Have testosterone \< 50 ng/dL. Note: Patients must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if th…