Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer

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. * Documented pain from bone metastases that requires opioid narcotic intervention. * Adopted a narcotic regimen that consists of one sustained release opioid agent taken daily for chronic pain and one immediate release opioid agent for breakthrough pain. * Received prior docetaxel and either abiraterone or MDV3100 treatment and has evidence of investigator assessed 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. * A left-ventricular ejection fraction (LVEF) of \>/= 50% assessed by echocardiogram or MUGA (multigated acquisition scan). * Capable of understanding and complying with the protocol requirements (including having the ability to access an interactive voice recognition system and self-report pain and narcotic use) 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 or mitoxantrone. * 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 therapy in the last 4 weeks (includes radiation targeting bone metastases), radionuclide treatment in the last 6 weeks, or radiation therapy to the thoracic cavity (unless radiation targets bone metastases) in the past 3 months. * Treatment with serotonergic psychiatric medication(s) in the last 2 weeks (5 weeks for fluoxetine). * Known brain metastases or uncontrolled epidural disease. * Requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or FXa (coagulation factor X) inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (above low dose levels for cardioprotection per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight heparin are permitted. * 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 of \> 0.5 teaspoon of red blood, 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. * Corrected QT interval (QTc) \> 500 ms in the last 4 weeks. * Unable to swallow capsules or tablets or tolerate infusions. * Previously-identified allergy or hypersensitivity to components of the study treatment formulations investigator or designee. * History of another malignancy (except non-melanoma skin cancer, adequately treated stage I colon cancer, superficial transitional carcinoma of the bladder) in the past 2 years.