Protocol Title:

Sunitinib Malate, Hormone Ablation, and External Beam Radiation for High-Risk and Locally Advanced Prostate Cancer

Protocol Status:

Pending

Protocol Number:

TBD

Type of Cancer:

High- Risk and Locally Advanced Adenocarcinoma of the Prostate Cancer

Principal Investigator:

Theodore DeWeese, M.D.

Research Nurse:

Shirl DiPasquale, R.N.

Phase Number:

I

General Eligibility:

Subjects must be male and 18 years of age or older with Advanced Adenocarcinoma of the Prostate (specific features listed in eligibility). Subjects can not have metastatic disease. ECOG performance status of 0-1. Patients must have a calculated creatinine clearance > than 35cc/min., an absolute neutrophil count > 1,500/mm2, platelets > or = to 100,000mm3, AST/ALT < 2.5 X UNL, and total bilirubin WNL. Subjects must not have had any prior VEGFR/PDGFR inhibitor or any other investigational therapy. Subject must have any uncontrolled cardiac condition, HIV, alcoholism, hepatitis, or liver disease.

Purpose:

Primary:
To define the tolerability of three different dose-levels of the antiogenesis inhibitor, sunitinib malate, in combination with hormone ablation and external beam radiation for advanced prostate cancer.

Secondary:
Describe the qualitative and quantitative toxicities. Evaluate putative biomarkers of outcome at baseline, after sunitinib lead-in and at 12 and 24 months after completion of radiation therapy. Explore the effects of sunitinib monotherapy during 4-week lead-in period prior to initiation of hormone ablation and radiation therapy on tumor hypoxia.

Treatment:

Once registered, treatment should be started preferably immediately but not later than 7 days. Patients will be treated with three different dos-levels of daily oral sunitinib for 4 weeks prior to initiation of external beam radiation therapy with combined androgen blockade. Following the lead-in period, external beam radiation (see section 4.3 of the protocol) will be initiated along with combined hormone ablation. Hormone ablation will be accomplished by leuprolide acetate or goserelin injections, every 3 months, in combination with oral bicalutamide (Casodex) for the first 2 weeks. Leprolide or goserelin therapy will continue for a period of 2 years. Sunitinib therapy will continue through the period external beam radiation to a total of 20 weeks (8weeks beyond completetion of radiation therapy).