Cabozantinib Plus Docetaxel and Prednisone for Advanced Prostate Cancer

• 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 National Cancer Institute (NCI) Pathology Department of the Walter Reed National Military Medical Center or YALE 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 to 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 computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam.
• 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 2.5 times upper limit of normal (ULN)
• ALT (SGPT) less than or equal to 2.5 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 ml/min/1.73 m^2 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 trial