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.

KEY INCLUSION CRITERIA

- mCRPC that includes visceral disease. Visceral metastatic disease is defined as solid
organ infiltration that is not bone or lymph node metastases.

KEY EXCLUSION CRITERIA

- Recent history (<6 months) of gastrointestinal hemorrhage requiring blood transfusion.

- Tumor involvement in the intestinal lining which the treating physician deems at risk
for perforation with rapid tumor response.