Inclusion Criteria:

Chemotherapy- and immunotherapy-naïve patients with progressive metastatic CRPC are
eligible.

- Age 18 or older, and be willing and able to provide informed consent.

- Histologically or cytologically confirmed adenocarcinoma of the prostate at either
MSKCC or at the participating site.

- Castrate serum testosterone level, ≤ 1.73 nmol/L (50 ng/dL), at the Screening visit.

- Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy
(ie, surgical or medical castration).

- Metastatic disease on imaging (e.g., bone scan, CT, MRI). Patients whose disease
spread is limited to regional pelvic lymph nodes are not eligible. If lymph node
metastasis is the only evidence of metastasis, it must be ≥ 2 cm in diameter.

- Progressive disease at study entry defined by PSA and/or radiographic criteria
according to the PCWG2.

- Karnofsky performance status of ≥80-100, and estimated life expectancy of ≥ 6 months.

- Toxicities related to prior therapy must either have returned to ≤ Grade 1 or
baseline or been deemed irreversible and in the opinion of the Investigator not
worsened.

- Able to swallow the study drug and comply with study requirements.

Exclusion Criteria:

- History of another malignancy within the previous 5 years other than nonmelanomatous
skin cancer.

- Absolute neutrophil count < 1,500/μL, or platelet count < 75,000/μL, or hemoglobin <
5.6 mmol/L (9 g/dL) at the Screening visit. (NOTE: patients may not have received any
growth factors within 7 days or blood transfusions within 28 days of the hematologic
laboratory values obtained at the Screening visit).

- Serum bilirubin ≥ 1.5 x ULN or for patients with Gilbert's disease, ≥3 mg/dL at the
Screening visit; AST or ALT ≥ 2.5 x ULN, (for patients with known liver metastasis,
AST or ALT ≤ 5 x ULN is allowed) at the Screening visit.

- Creatinine > 177 μmol/L (2 mg/dL), albumin < 30 g/L (3.0 g/dL), potassium ≤ 3.5 mEq/L
at the Screening visit.

- Clinically significant cardiovascular disease including myocardial infarction within
6 months, uncontrolled angina within 3 months, congestive heart failure New York
Heart Association (NYHA) class 3 or 4, uncontrolled hypertension as indicated by
systolic blood pressure > 160 mmHg or diastolic blood pressure > 95 mmHg at the
Screening visit.

- Major surgery or radiation therapy within 4 weeks of enrollment (Day 1 Visit).

- Treatment with antiandrogens (eg, bicalutamide, flutamide, or nilutamide) within 4
weeks of enrollment (Day 1 visit). Concomitant therapy with any of the agents listed
in Section 4.3.2 is prohibited.

- History of progression of prostate cancer disease while receiving ketoconazole. Prior
use or participation in a clinical trial of an investigational agent that blocks
androgen synthesis (eg, abiraterone acetate, TAK-700, TAK-683, TAK-448),
chemotherapy, or immunological agents (eg, immune modulators, cytokines, vaccines, or
antibody-delivered chemotherapy). The use of denosumab for bone metastasis is
permitted.

- Known allergy to any of the compounds under investigation.

- The patient has uncontrolled or significant medical condition other than cancer, that
would prevent the participation in the study or make this protocol unreasonably
hazardous, in the opinion of the investigator, including but not limited to:

- Autoimmune disease: Patients with a history of inflammatory bowel disease, including
ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients
with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive
sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg,
Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (eg,
Guillain-Barre syndrome and myasthenia gravis).

- Known or suspected brain metastasis, or untreated leptomeningeal disease.

- Active infection or other medical condition that would make prednisone use
contraindicated.

- Active or symptomatic viral hepatitis or chronic liver disease.