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