A 2 Part Phase 2 Trial of Galeterone in the Treatment of Castration Resistant Prostate Cancer (ARMOR2)

• Part 1 will confirm dose to be used in Part B of the study by assessing safety and efficacy by means PSA response. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  This study will monitor frequency and severity of adverse events and changes in laboratory values. This study will also assess changes in levels of prostate specific antigen as a measure of treatment response
• Part 2 of this study will further assess efficacy of the dose of galeterone chosen in Part 1 of the study in terms of changes from baseline in PSA concentration and tumor response rate by RECIST criteria (v.1.1) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  RECIST will be evaluated by tumor changes measurements as seen on CT/MRI.

This is a Phase 2, randomized, 2 part trial that will evaluate the safety and efficacy of galeterone in castration resistant prostate cancer (CRPC) patients. This trial will enroll patients who have not yet received androgen directed hormonal therapies (e.g. TAK-700, ARN-509, ketoconazole, enzalutamide, or galeterone) for the treatment of prostate cancer (treatment naïve) as well as CRPC patients who demonstrated disease progression while on the hormonal therapy Zytiga® (abiraterone acetate).

This trial will be split into two parts. The purpose of Part 1 will be to confirm dose and target patient population and Part 2 will be expansion of the dose and patient population selected in Part 1. For eligible patients, there will be an optional extension dosing following the completion of Part 1 or Part 2 of the trial.

Obtaining of informed consent and screening may be performed up to 28 days prior to enrollment. Each patient will be able to receive his specified regimen for 3 consecutive cycles. Each cycle consists of 28 days (approximately 1 mo.). End of Cycle 3 visit assessments will be used to determine outcome and dosing may continue up to an additional 2 weeks until the results of all assessments are obtained. Eligible patients may continue treatment in an optional extension period following the completion of the primary parts of this trial.

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