Denosumab Plus Enzalutamide, Abiraterone and Prednisone Compared to Denosumab Plus Enzalutamide Alone for Men With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastases

Inclusion Criteria:

- Histologic proof of adenocarcinoma of the prostate with clinical evidence of
metastatic disease to the bone.

- Castrate resistant progression of prostate carcinoma, as shown by:

- Serum testosterone level <50 ng/dL or prior bilateral orchiectomy. Treatment to
maintain castrate levels of testosterone should continue, and

- Either symptomatic progression, or, if patient is asymptomatic then a rising
serum PSA in two occasions at least 1 week apart, with minimum pre-treatment
serum PSA of 5 ng/dL.

- Patients with nodal disease are eligible.

- Bi-dimensionally measurable disease within the bone.

- Life expectancy of at least 12 weeks.

- ECOG Performance status < 2

- Adequate:

- Bone marrow function; absolute neutrophil count > 1,500 mm3, platelet count of >
100,000 mm3 and hemoglobin > 9.0 gm/dl.

- Hepatic function; SGOT/SGPT and conjugated bilirubin less than twice the upper
limit of normal.

- Renal function; serum creatinine ≤ 2 mg/dL (or, if creatinine > 2 mg/dL, then a
creatinine clearance of at least 35 ml/min (measured or estimated by the Cockroft
formula:

CLcr = [(140-age) x wt (kg)]/[72 x serum creatinine (mg/dL)].

- No evidence of coagulopathy as indicated by PT < 1.5X upper limit of normal.

- Serum calcium (corrected) from 8 to11.5 mg/dL (2 to 2.9 mmol/L) - Patients must sign
an informed consent indicating that they are aware of the investigational nature of
the study.

Exclusion Criteria:

- Patients with variant histologies (e.g., ductal or small cell carcinoma).

- Patients with visceral disease are ineligible.

- Patients who have had prior Sipuleucel-T, docetaxel, cabazitaxel, abiraterone or
enzalutamide as a single agent, or in combination therapy.

- Concurrent cancer chemotherapy, radiotherapy or surgery.

- Concurrent serious infection.

- Life threatening illness (e.g., congestive heart failure, uncontrolled angina or
myocardial infarction in the prior six months).

- Hypertension uncontrolled by medication.

- Patients who are known to require invasive dental procedures.

- No known or suspected brain metastases (NOTE: patients with treated epidural disease
are allowed)

- Administration of any investigational drug within 28 days prior to receipt of
denosumab.

- Age ≤ 18 years of age