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 they have not undergone orchiectomy
• •White blood cells \>= 1.5 x 10\^9/L (obtained within 14 days prior to treatment start)
• •Platelets (UNVPLT) \>= 100 x 10\^9/L (obtained within 14 days prior to treatment start)
• •Hemoglobin (HGB) \>= 9 g/dL (obtained within 14 days prior to treatment start)
• •Potassium (K), total calcium (CA) (corrected for serum albumin), magnesium, sodium (NA) and phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication (obtained within 14 days prior to treatment start)
• •International normalized ratio (INR) =\< 1.5 (obtained within 14 days prior to treatment start)
• •Serum creatinine (CREAT) =\< 1.5 mg/dL or creatinine clearance \> 50 mL/min (obtained within 14 days prior to treatment start)
• •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN. If the patient has liver metastases, ALT and AST must still be =\< 2.5 x ULN. Patients with liver metastases and AST/ALT above this limit will not be enrolled (obtained within 14 days prior to treatment start)
• •Total serum bilirubin =\< 1.5 x ULN; or total bilirubin (TBILI) =\< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert?s syndrome (obtained within 14 days prior to treatment start)
• •Ability to swallow and retain oral medication (without crushing, dissolving or chewing tablets)
• •Phase Ib only: Prior enzalutamide treatment and/or other approved treatments for CRPC are acceptable
• •Phase II only: Participants MUST be treatment na?ve in the CRPC setting: i.e., no prior exposure to abiraterone acetate other specific CYP-17 inhibitors; no prior exposure to enzalutamide or investigational androgen receptor (AR) targeted agents; and no prior exposure to chemotherapy and or RAD-223
• •Sexually active males must agree to use a condom during intercourse while taking the study drug and for at least 3 months after stopping study treatment. Sexually active males should not father a child during this period. A condom is required to be used by vasectomized men in order to prevent delivery of the drug via seminal fluid. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately
• •Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure