A Phase II Trial of Cabozantinib (XL184) in Patients With 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
or 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

- Allergy to doxycycline or other tetracyclines

- 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.