A Study to Determine the Safety and Efficacy of Cabozantinib (XL184) in Patients with Metastatic Castration-resistant Prostate Cancer who have Received Prior Docetaxel and Prior Abiraterone or MDV3100

INTERVENTION: Product Name: Cabozantinib 20mg Product Code: XL184 Pharmaceutical Form: Tablet INN or Proposed INN: Cabozantinib CAS Number: 1140909‐48‐3 Current Sponsor code: XL184 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: APO‐PREDNISONE Product Name: Prednisone Pharmaceutical Form: Capsule, hard INN or Proposed INN: PREDNISONE CAS Number: 53‐03‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: Cabozantinib 60mg Product Code: XL184 Pharmaceutical Form: Tablet INN or Proposed INN: Cabozantinib CAS Number: 1140909‐48‐3 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 60‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Metastatic Castration‐resistant Prostate Cancer (CRPC) ; MedDRA version: 17.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: The objective of this study is to evaluate the effect of cabozantinib compared to prednisone on overall survival in men with previously treated metastatic castration‐resistant prostate cancer with bone‐dominant disease who have experienced disease progression on docetaxel‐containing chemotherapy and abiraterone or MDV3100. ; Primary end point(s): Overall survival Secondary Objective: None. Timepoint(s) of evaluation of this end point: Overall survival is defined as the time from the date of randomization to the date of death (due to any cause). Subjects not known to have expired at the time of analysis will generally be censored at the date last known alive. Detailed censoring rules for overall survival will be described in the SAP. SECONDARY OUTCOME: Secondary end point(s): Bone scan response at the end of Week 12 by IRF. The stratified CMH test will be used as the primary analysis of this endpoint. Timepoint(s) of evaluation of this end point: Week 12 INCLUSION CRITERIA: 1. Documented histological or cytological diagnosis of prostate cancer. 2. Serum testosterone levels less than 50 ng/dL (< 1.75 nmol/L) within 28 days before randomization. 3. Evidence of bone metastasis related to prostate cancer on bone scans from a protocol‐credentialed scanner within 28 days before randomization. 4. The subject must have received prior docetaxel (minimum cumulative dose of 225 mg/m2) and either abiraterone or MDV3100 treatment and have evidence of investigator‐assessed prostate cancer progression on each agent independently. For docetaxel: subjects must have progressed during or after docetaxel‐containing therapy. For abiraterone or MDV3100: subjects must have experienced disease progression during abiraterone or MDV3100 therapy. Prostate cancer progression is defined as: a. PSA progression according to modified PCWG2 (Prostate Cancer Working Group 2) criteria: PSA level of at least 2 ng/mL (2 µg/L) which has su