A Study of BAY 43-9006 in Combination With Bicalutamide in Patients With Chemo-Naïve Hormone Refractory Prostate Cancer

Justification: The biologic and clinical activity and tolerability of BAY 43-9006, the therapeutic needs of the proposed patient population, and the experimental evidence in support of targeting the VEGF/VEGFR and MAPK pathways in combination with androgen receptor blockade in prostate cancer, provides a strong rationale for the proposed phase II trial to evaluate the tolerability and anti-cancer activity of combined treatment with the non-steroidal anti-androgen bicalutamide with the multi-targeted kinase inhibitor BAY 43-9006 in patients with prostate cancer that is progressing after castration therapy. Objectives: The primary study objective is to define the efficacy (i.e. post treatment decrement in PSA (PSA response)) of BAY 43-9006 in combination with bicalutamide in patients with chemo-naïve hormone-refractory prostate cancer. Secondary Objectives: * To determine the safety and tolerability of BAY 43-9006 given in combination with bicalutamide in patients with HRPC. * To determine the time to treatment failure, PSA progression and disease progression in HRPC patients treated with BAY 43-9006 in combination with bicalutamide. * To determine objective response rates in HRPC patients with measurable disease treated with BAY 43-9006 in combination with bicalutamide. Research Method: This is a phase II clinical trial in patients with androgen independent prostate cancer which will evaluate the therapeutic activity and safety profile of BAY 43-9006 given orally at the recommended phase II dose of 400 mg PO BID continuously in combination with bicalutamide 50 mg PO daily continuously. Each 4 week period will be considered 1 cycle. Doses will be adjusted for toxicity. Statistical Analysis: Primary Endpoint The primary endpoint for this study will be the rate of PSA-response of the combination for patients with rising PSA post castration therapy. Secondary Endpoints: Secondary endpoints will include time to treatment failure, time to PSA progression, duration of PSA response, median survival time, 1 year survival rate, objective tumor response rate and stable disease rate as defined by the RECIST criteria, response duration, and incidence of toxicities by NCI CTCAE.