Inclusion Criteria

Key Inclusion Criteria

- The subject has a proven histologic diagnosis of prostate adenocarcinoma, but may
have undergone prior surgery and/or radiation

- The subject must currently have castration resistant prostate cancer defined as 2
serial rising prostate-specific antigens (PSAs) with a castrate level of testosterone
(< 50 ng/dL)

- A subject with non-metastatic castration-resistant prostate cancer (CRPC) may not
have received prior chemotherapy unless in the neoadjuvant or adjuvant setting > 24
months ago and may not have received prior zoledronic acid or denosumab

- A subject with metastatic CRPC must have bone metastases accessible for biopsy by
computed tomography (CT) guidance

- The subject must be willing to undergo sequential biopsy of bone or bone metastases

- Adequate organ and bone marrow function.

- The subject is capable of understanding and complying with the protocol requirements
and has signed the informed consent document

Key Exclusion Criteria

- Prior treatment with cabozantinib and other met inhibitors

- Cytotoxic chemotherapy or biologic agents within 3 weeks of study treatment

- Recent radiation therapy (3 months for thoracic cavity, 14 days for bone or brain
metastasis, 28 days for other sites) or radionuclide treatment within 6 weeks of
starting study drug.

- 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 from toxicities due to all prior therapies except
alopecia and other non-clinically significant adverse events (AEs)

- The subject has primary brain tumor or active brain metastases or epidural

- Coagulation tests need to be adequate for the study

- The subject requires concomitant treatment, in therapeutic doses, with anticoagulants
such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa
inhibitors, or antiplatelet agents (eg, clopidogrel); low dose aspirin (=< 81
mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight
heparin (LMWH) are permitted

- The subject requires chronic concomitant treatment of strong cytochrome P450, family
3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin,
carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort)

- History of clinically significant gastrointestinal bleeding

- The subject has uncontrolled, significant intercurrent or recent illness

- The subject is unable to swallow tablets

- The subject has a corrected QT interval (QTcF) > 500 ms within 28 days before day 1
of cycle 1

- The subject has a previously identified allergy or hypersensitivity to components of
the study treatment formulation or to tetracycline