This is an open-label phase 2 multi-center study of abiraterone and enzalutamide in men with castration-resistant prostate cancer. Sixteen patients will be enrolled over 18 months.

Inclusion Criteria:

• Patients with histologically or cytologically confirmed prostate cancer

• Able to read and understand the consent form, either alone or with the aid of a translator

• Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nmol/L). If the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patients who have not undergone orchiectomy), they must remain on continuous androgen suppression therapy throughout the study

• Patients receiving bone-targeted therapies must be on stable doses for at least 4 weeks prior to enrollment

• Historical frozen/paraffin-embedded diagnostic tissue specimens are available for analysis (i.e. radical prostatectomy or biopsy tissue)

• Documented metastatic disease by positive bone scan or metastatic lesions (on CT or MRI) that can be biopsied with an anticipated minimum of 4 cores, as assessed by the local radiologist

• prostate cancer progression at study entry defined as one or more of the following criteria: i. Rising PSA: minimum of two rising PSA levels with an interval of ≥ 1 week between each determination ii. Soft tissue disease progression, as defined by RECIST 1.1 iii. Bone disease progression, as defined by PCWG2 with two or more new lesions on bone scan

• PSA value at screening visit ≥ 2 µg/L (2 ng/mL)

• ECOG performance status 0-2

• Adequate organ and BM function, as defined by the following criteria:

  i. absolute neutrophil count ≥1,500/µL ii. platelets ≥100,000/µL iii. total bilirubin ≤1.5 × institutional upper limit of normal (ULN) iv. AST(SGOT) or ALT(SGPT) ≤2.5 × institutional ULN v. creatinine ≤1.5 × institutional ULN or below

• Serum albumin ≥ 3.0 g/dL

• Serum potassium ≥ 3.5 mmol/L

• Haemoglobin ≥ 10.0 g/dL, independent of transfusion

• Asymptomatic or mildly symptomatic from prostate cancer

• Life expectancy of > 6 months

• Able to swallow study drugs

• Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 13 weeks after last study drug administration

Exclusion Criteria:

• Patients with known hypersensitivity or allergy to abiraterone acetate, enzalutamide or any of their excipients.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (NYHA Class 3 or greater), cirrhosis with a Child-Pugh level of B or greater or evidence of cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, myocardial infarction within 6 months, hypotension (defined by systolic blood pressure < 86 mmHg at Screening visit), hypertension (defined by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at Screening visit), bradycardia (defined by < 50 beats per minute on ECG performed at screening), active peptic ulcer disease, clinically significant gastrointestinal conditions (e.g. Crohns disease, ulcerative colitis), any seizure disorder or psychiatric illness, and social situations that would limit compliance with study requirements
• Active invasive malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin
• Known or suspected brain metastasis or leptomeningeal disease
• Radiotherapy within the past 4 weeks, except for low dose palliative radiation to bone of ≤5 fractions
• Treatment with 5-α reductase inhibitors (finasteride, dutasteride), androgen receptor antagonists (bicalutamide, nilutamide, flutamide), estrogens, cyproterone within 4 weeks of Day 1 visit