Inclusion Criteria:

1. Male age > 18 years

2. Histologically or cytologically confirmed adenocarcinoma of the prostate (excluding
neuroendocrine differentiation or small cell histology)

3. Ongoing androgen blockade (therapy with gonadotropin-releasing hormone (GnRH)
analogues, or orchiectomy) demonstrated by serum testosterone concentration of less
than 50 ng/dL.

4. Demonstration of progression while on androgen blockade (based upon PCWG2
guidelines).

5. Eastern Cooperative Oncology Group (ECOG) Performance Status <2

Exclusion Criteria:

1. Prior treatment with androgen directed hormonal therapies (prior abiraterone
treatment allowed for some study arms)

2. Prior chemotherapy (unless allowed for some study arms).

3. Treatment with non-steroidal oral antiandrogens within 4 weeks of enrollment

4. Prior use of any chronic systemic glucocorticoids .

5. Prior radiation therapy within 3 weeks and radionuclide therapy within 8 weeks of
enrollment

6. Prior treatment with Alpharadin® (radium-223 chloride)

7. Treatment with anti arrhythmia therapy for ventricular arrhythmia < 4 weeks prior to
enrollment

8. Treatment with Coumadin® (warfarin sodium) or other anti-coagulant therapy (except
aspirin) < 4 weeks prior to enrollment

9. Severe systemic diseases or active uncontrolled illnesses.

10. Abnormal heart function

11. Liver metastases

12. Brain metastases (unless stable disease >3 mos. by scan without additional
CNS-directed therapy)

13. The patient has known allergy to any of the treatment components

14. Any physical or mental condition or social situation that in the opinion of the
Investigator may interfere with the patient's ability to comply with the trial
procedures

15. History of excessive alcohol consumption

16. Use of any substance known to cause AME