A Phase II Study of Cabozantinib (XL184) Therapy in Castrate Resistant Prostate Cancer (CRPC) With Visceral Metastases

Cabozantinib (XL184), a multi-targeted tyrosine kinase inhibitor, has demonstrated a powerful clinical phenotype in men with metastatic castrate resistant prostate cancer (mCRPC) both before and after chemotherapy. This phenotype consists of rapid reduction in pain (when present) and improvement in bone scans that may or may not be accompanied by decrease in serum prostate specific antigen (PSA) concentrations. In previous studies of cabozantinib in advanced prostate cancer, patients with visceral disease have been excluded. Hence, this protocol creates a unique opportunity to define the activity of this disease in the population of men with visceral disease - a marker for poorer prognosis in mCRPC. Primary Objectives: - To assess the clinical benefit (complete response + partial response + stable disease) of cabozantinib in patients with mCRPC with visceral metastases. Secondary Objectives: To assess the impact of cabozantinib on numbers live circulating tumor cells (CTCs) using NanoVelcro Chips To test the feasibility of measuring variation in gene expression in circulating tumor cells (CTCs) in response to therapy. To determine if there is an impact of cabozantinib on live circulating tumor cell (CTC) number and patterns of gene expression. To measure the impact of cabozantinib on serum HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor) levels in men with metastatic, castration-resistant prostate cancer (mCRPC). To assess the safety and tolerability of lower doses (i.e. doses below 100 mg daily) of cabozantinib in mCRPC with visceral involvement. To collect blood, urine, tissue, and plasma which may be used determine if there are germline genetic variations that correlate with toxicity. To pilot correlations between molecular content between circulating tumor cells (CTCs), large oncosomes, and tumor tissue.