Cabozantinib-S-Malate in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer

Inclusion Criteria

• The subject has histologically confirmed prostate adenocarcinoma with radiologic evidence of metastases
• If patient are on anti-androgens, these should be discontinued, at least 4 weeks prior for flutamide and at least 6 weeks for bicalutamide or nilutamide
• At least 14 days should have elapsed from prior radiation therapy to bone metastases from prostate cancer
• The patient has received a maximum of one prior chemotherapy regimen for metastatic prostate cancer
• Patients must demonstrate disease progression on or after most recent systemic therapy, either by prostate-specific antigen (PSA), new bone metastases or by measurable disease criteria per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
• Patients should have received either luteinizing hormone-releasing hormone (LHRH) analogue, or LHRH analogue and anti- androgen for metastatic prostate cancer
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Bisphosphonate therapy can be continued if started prior to protocol enrollment
• Patients must have blood pressure (BP) readings = 1500/mm^3 without colony stimulating factor support
• Platelets >= 100,000/mm^3
• Hemoglobin >= 9 g/dL
• Bilirubin = = 2.8 g/dl
• Serum creatinine = = 50 mL/min; for creatinine clearance estimation, the Cockcroft and Gault equation should be used
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = = lower limit of normal (LLN)
• The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
• Patients participating in this trial must also be eligible and willing to sign consent for participation in [2'-18F]-1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine (FMAU) and 18F-flouride positron emission tomography (PET) scans done under separate protocols
• Sexually active subjects (men) must agree to use medically accepted barrier methods of contraception (eg, male condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used by the female partner; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control
• Projected life expectancy of at least 6 months
• No prior history of other malignancies in the last 3 years, except for squamous and basal cell skin cancer

Exclusion Criteria

• The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
• Prior treatment with cabozantinib
• The subject has received radiation therapy:
• To the thoracic cavity or gastrointestinal tract within 3 months of the first dose of study treatment
• To bone or brain metastasis within 14 days of the first dose of study treatment
• To any other site(s) within 28 days of the first dose of study treatment
• The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
• The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; patients receiving LHRH or gonadotropin-releasing hormone (GnRH) agonists to maintain castrate levels of testosterone or patients on bisphosphonate/denosumab, may be maintained on these agents
• The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
• The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) = = 1.3 x the laboratory ULN
• The subject requires concomitant treatment, in therapeutic doses, with