This study will 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.

Inclusion Criteria:

• Histological or cytological diagnosis of castration resistant prostate cancer (serum testosterone less than 50 ng/dL).
• Evidence of bone metastasis related to prostate cancer on bone scans.
• Received prior docetaxel (minimum cumulative dose of 225 mg/m2) and either abiraterone or MDV3100 treatment and has evidence of prostate cancer progression on each agent independently.
• Maintenance of LHRH agonist or antagonist unless treated with orchiectomy.
• Recovered from toxicities related to any prior treatments, unless the toxicities are clinically non significant or easily manageable.
• Adequate organ and marrow function.
• Capable of understanding and complying with the protocol requirements and signed the informed consent form.
• Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.

Exclusion Criteria:

• Prior treatment with cabozantinib.
• Treatment with docetaxel, abiraterone, or MDV3100 in the last 2 weeks; or with any other type of cytotoxic or investigational anticancer agent in the last 2 weeks.
• Radiation within 4 weeks (excluded if to mediastinum) or radionuclide treatment within 6 weeks of randomization.
• Known brain metastases or cranial epidural disease.
• Requires concomitant treatment, in therapeutic doses, with anticoagulants.
• Requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort).
• Uncontrolled, significant intercurrent illness including, but not limited to, cardiovascular disorders, gastrointestinal disorders, active infections, non-healing wounds, recent surgery.
• Clinically significant hematemesis or hemoptysis, or other signs indicative of pulmonary hemorrhage in the last 3 months, or history of other significant bleeding in the past 6 months.
• Cavitating pulmonary lesion(s) or a lesion invading or encasing a major blood vessel.
• QTcF > 500 ms within 7 days of randomization.
• Unable to swallow capsules or tablets.
• Previously-identified allergy or hypersensitivity to components of the study treatment formulations.
• Another diagnosis of malignancy requiring systemic treatment within 2 years of randomization.