Trial of Cabozantinib (XL184) in Castrate-Resistant Prostate Cancer Metastatic to Bone

Inclusion Criteria:

Pathologically and radiologically confirmed castrate-resistant prostate cancer metastatic to bone
Bone metastases which are accessible for biopsy under CT guidance.
Willingness to undergo sequential biopsy of bone lesions.
No prior standard chemotherapy for metastatic disease (neoadjuvant, adjuvant and hormonal treatments are excluded).
Participant must have discontinued antiandrogen therapy at least 4 weeks (for flutamide and megestrol acetate) or 6 weeks (for bicalutamide or nilutamide) prior to the first dose of XL184. Participants currently on LHRH or GnRH agonists can be maintained on these agents.
Greater than or equal to 18 years old on day of consent
Participants must be able to care for themselves
Adequate organ and bone marrow function
Participants must be capable of understanding and complying with the protocol requirements and has signed the informed consent document.
Men capable of sexual activity will be required to agree to use a condom during sexual contact with women having the potential to bear children during their participation in the study and for six months after participation.

Exclusion Criteria:

Prior therapy with cabozantinib
Any other type of investigational agent within 28 days before the first dose of study treatment or 5 half-lives of the compound or active metabolite, whichever is longer
No radiation therapy within 14 days of study treatment. No radionuclide treatment within two months.
No known brain metastases.
Test results that measure how quickly blood clots need to be adequate for the study
Participants who require concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted.
Participants must not have uncontrolled significant illness including but not limited to: ongoing or active infection requiring systemic treatment, symptomatic congestive heart failure, uncontrolled hypertension , history of hypertensive emergency (e.g.encephalopathy) or hypertensive urgency within 6 months of study treatment, clinically significant wounds including osteonecrosis, history of organ transplant, unstable angina pectoris, stroke within 3 months of study drug, heart attack within 3 months of study drug, development of clots within blood vessels within 6 months of study drug, bleeding from distended veins within 3 months of study drug, any other severe or life threatening hemorrhage/bleeding, major surgery within 4 weeks of study treatment, clinically significant cardiac arrhythmias, history of bowel obstruction within 6 months of study drug or unresolved malabsorption syndrome, untreated bone fracture including tumor-related pathologic fracture, anticipated need for major surgery during the period of the study.
Corrected QT interval, as measured by an ECG, must be within acceptable protocol limits within 28 days of entering the study
Unable to swallow capsules
Unable to undergo MRI
History of another malignant disease within two years with the exception of superficial skin or bladder cancer which has been completely resected or carcinoma in situ without evidence of invasion.