Inclusion Criteria

- INCLUSION CRITERIA:

- Must have metastatic, progressive, castrate resistant prostate cancer (CRPC). There
must be radiographic evidence of disease after primary treatment with surgery or
radiotherapy that has continued to progress radiographically or biochemically (rising
PSA levels on successive measurements) despite adequate androgen-deprivation therapy,
which is defined as having undergone bilateral surgical castration or continued
treatment on GnRH agonists or antagonists.

Progression must be evidenced and documented by any of the following parameters:

- Two consecutively rising PSA values, above the baseline, at a minimum of 1- week
intervals

- Appearance of one or more new lesions on bone scan

- Progressive measurable disease by RECIST 1.1

The use of androgen receptor inhibitors is not required prior to study entry. For those
patients receiving an anti-androgen agent (flutamide, bicalutamide, or nilutamide), for at
least 6 consecutive months immediately prior to study entry, and are entering the trial
due to a rise in PSA, they must demonstrate a continued rise in PSA within 4 weeks after
stopping flutamide and within 6 weeks after stopping bicalutamide or nilutamide.
Flutamide, nilutamide and bicalutamide disease progression requirements only apply to
patients who have been on these drugs for at least the prior 6 months.

- Histopathological confirmation of prostate cancer by the Laboratory of Pathology of
the NCI or Pathology Department of the Walter Reed National Military Medical Center
is required prior to entering this study. Patients whose pathology specimens are no
longer available may be enrolled if the patient has a clinical course that is
consistent with prostate cancer and available documentation from an outside pathology
laboratory of the diagnosis. All efforts should be made to have the material
forwarded o the research team for use in correlative studies in cases where original
tissue blocks or archival biopsy material is available.

- Patients must have metastatic disease, defined as at least one lesion on bone scan or
at least one lesion that can be accurately measured in at least one dimension
(longest diameter to be recorded for non-nodal lesions and short axis for nodal
lesions) as greater than or equal to 20 mm with conventional techniques or as greater
than or equal to 10 mm with spiral CT scan, MRI, or calipers by clinical exam.

- Patients must have a life expectancy of greater than 3 months.

- Patients must have a performance status of 0 to 2 according to the ECOG criteria.

- Patients must have adequate bone marrow, hepatic, and renal function with:

- Hemoglobin greater than or equal to 9 grams per deciliter

- Leukocytes greater than or equal to 3000 per microliters

- ANC greater than or equal to 1500 per microliters, without CSF support

- Platelets greater than or equal to 100,000 per microliters

- AST(SGOT) less than or equal to 1.5 times upper limit of normal (ULN)

- ALT(SGPT) less than or equal to 2.0 times upper limit of normal (ULN)

- Total serum bilirubin less than or equal to the upper limit of normal (ULN)

- Serum albumin greater than or equal to 2.8 grams per deciliters

- Serum phosphorus, calcium, magnesium, and potassium greater than or equal to LLN

- Lipase less than 2.0 times the upper limit of normal and no radiologic or
clinical evidence of pancreatitis

- Creatinine less than or equal to 1.5 times institutional upper limits of normal

OR

- creatinine clearance of greater than or equal to 50 Glomerular Filtration Rate for
patients with creatinine levels above institutional normal by 24 hour urine.

- urine protein/urine creatinine ratio (UPCR) less than or equal to 1

- Patients must be at least 18 years of age. Because no dosing or adverse event
data are currently available on the use of cabozantinib in combination with
docetaxel and prednisone in patients less than 18 years of age, children are
excluded from this study, but may be eligible for future pediatric trials

- Patient must be capable of understanding and complying with protocol
requirements and is willing to give informed consent

- Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and 4
months after completion of XL184 administration. Sexually active fertile
patients and their partners must agree to use medically accepted barrier methods
of contraception (e.g., male or female condom) for the duration of study
participation, and for 4 months after the last dose of the study drug(s). Should
a woman become pregnant or suspect she is pregnant while her partner is
participating in this study, she should inform her treating physician
immediately.

- Technetium 99 bone scintigraphy scan

EXCLUSION CRITERIA:

- The subject has had evidence within 2 years of the start of study treatment of
another malignancy which required systemic treatment

- The subject is unable to swallow tablets

- Patient with radiographic evidence of cavitating pulmonary lesion(s)

- The subject has tumor in contact with or encasing a major blood vessel

- The subject has a primary brain tumor

- The subject has active brain metastases or epidural disease Subjects with brain
metastases previously treated with whole brain radiation or radiosurgery or subjects
with epidural disease previously treated with radiation or surgery who are
asymptomatic and do not require steroid treatment for at least 2 weeks before
starting study treatment are eligible. Neurosurgical resection of brain metastases or
brain biopsy is permitted if completed at least 3 months before starting study
treatment. Baseline brain scans are not required to confirm eligibility.

- 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 (e.g., clopidogrel). Low dose aspirin (less than
or equal to 81 milligrams per day), low-dose warfarin (less than or equalt to1
milligrams per day), and prophylactic low molecular weight heparin (LMWH) are
permitted.

- The subject has a corrected QT interval calculated by the Fridericia formula (QTcF)
greater than 500 milliseconds within 28 days before initiation of protocol therapy.
Note: if initial QTcF is found to be greater than 500 milliseconds, two additional
EKGs separated by at least 3 minutes should be performed. If the average of these
three consecutive results for QTcF is less than or equal to 500 milliseconds, the
subject meets eligibility in this regard.

- Patients with contraindication to steroid use

- Prior treatment with cabozantinib

- Patient has been treated with docetaxel for metastatic disease

- The patient has received cytotoxic chemotherapy (including investigational cytotoxic
chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or
nitrosoureas or mitomycin within 6 weeks before 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 with the exception of patients receiving
prior abiraterone or ketoconazole. For patients receiving prior abiraterone or
ketoconazole, they must discontinue the medication within 5 half lives of the
compound before the first dose of study treatment in order to participate in this
study. Note: Subjects with prostate cancer currently receiving LHRH or GnRH agonists
must 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 received radiation therapy:

- to the thoracic cavity or gastrointestinal tract within 3 months before the
first dose of study treatment

- to bone or brain metastasis within 14 days before the first dose of study
treatment

- to any other site(s) within 28 days before the first dose of study treatment

- The subject has received radionuclide treatment within 6 weeks prior to the first
dose of the study treatment

- The subject has not recovered to baseline or CTCAE less than or equal to Grade 1 from
toxicity due to all prior therapies, including surgery, except alopecia and other
non-clinically significant AEs

- The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or
partial thromboplastin time (PTT) test results at screening greater than or equal 1.3
times the laboratory ULN within 7 days before the first dose of study treatment

- The subject has experienced any of the following:

- clinically-significant hematemesis or gastrointestinal bleeding within 6 months
before the first dose of study treatment

- hemoptysis of greater than or equal to 0.5 teaspoon (2.5 mL) of red blood within
3 months before the first dose of study treatment

- any other signs indicative of pulmonary hemorrhage within 3 months before the
first dose of study treatment

- The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or
large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor
within 28 days before the first dose of cabozantinib

- The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:

- Cardiovascular disorders including

- Congestive heart failure (CHF): New York Heart Association (NYHA) Class III
(moderate) or Class IV (severe) at the time of screening

- Concurrent uncontrolled hypertension defined as sustained BP greater than
140 millimeters of mercury systolic, or greater than 90 millimeters of
mercury diastolic despite optimal antihypertensive treatment (BP must be
controlled at screening)

- Any history of congenital long QT syndrome

- Any of the following within 6 months before the first dose of study
treatment:

- unstable angina pectoris

- clinically-significant cardiac arrhythmias

- stroke (including TIA, or other ischemic event)

- myocardial infarction

- thromboembolic event requiring therapeutic anticoagulation (Note:
subjects with a venous filter (e.g. vena cava filter) are not
eligible for this study)

- Gastrointestinal disorders particularly those associated with a high risk of
perforation or fistula formation including:

- Any of the following within 28 days before the first dose of study
treatment

- intra-abdominal tumor/metastases invading GI mucosa (Bullet) active
peptic ulcer disease

- inflammatory bowel disease (including ulcerative colitis and Crohn's
disease), diverticulitis, cholecystitis, symptomatic cholangitis or
appendicitis

- Any of the following within 6 months before the first dose of study
treatment:

- history of abdominal fistula

- gastrointestinal perforation

- bowel obstruction or gastric outlet obstruction

- intra-abdominal abscess. Note: Complete resolution of an
intra-abdominal abscess must be confirmed prior to initiating
treatment with cabozantinibeven if the abscess occurred more than 6
months ago.

- Other disorders associated with a high risk of fistula formation including PEG
tube placement within 3 months before the first dose of study therapy or
concurrent evidence of intraluminal tumor involving the trachea and esophagus.

- Other clinically significant disorders such as:

- active infection requiring systemic treatment within 28 days before
the firstdose of study treatment

- serious non-healing wound/ulcer/bone fracture within 28 days before
the first dose of study treatment

- history of organ transplant

- concurrent uncompensated hypothyroidism or thyroid dysfunction within
7 days before the first dose of study treatment

- history of major surgery as follows:

- Major surgery within 3 months of the first dose of cabozantinib
if there were no wound healing complications or within 6 months
of the first dose of cabozantinib if there were wound
complications

- Minor surgery within 1 months of the first dose of cabozantinib
if therewere no wound healing complications or within 3 months of
the first dose of cabozantinib if there were wound complications.

In addition, complete wound healing from prior surgery must be confirmed at least 28 days
before the first dose of cabozantinib irrespective of the time from surgery

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with the study agents. In addition,
these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

- Patients who require taking drugs that are strong inhibitors/inducers of CYP3A4 and
cannot be switched to an alternative medication.

Because the lists of these agents are constantly changing, it is important to regularly
consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/;
medical reference texts such as the Physicians' Desk Reference may also provide this
information. As part of the enrollment/informed consent procedures, the patient will be
counseled on the risk of interactions with other agents, and what to do if new medications
need to be prescribed or if the patient is considering a new over-thecounter medicine or
herbal product.

-Patients with greater than or equal to grade 2 peripheral neuropathy at baseline.