A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) Versus Prednisone in Metastatic Castration-resistant Prostate Cancer Patients Who Have Received Prior Docetaxel and Prior 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 3
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.

- Liver or brain metastases or cranial epidural disease.

- Requires concomitant treatment, in therapeutic doses, with anticoagulants
antiplatelet agents.

- 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 in the last 5 years.