Study of PTK787 in the Treatment of Patients With Non-Metastatic Androgen Independent Prostate Cancer

Phase II Evaluation of PTK787, an Oral Vascular Endothelial Growth Factor Inhibitor, in Patients With Non-Metastatic Androgen Independent Prostate Cancer

The purpose of this study is to evaluate PTK787/ZK 222584, a drug that blocks new blood vessel growth, in the treatment of patients with non-metastatic androgen independent prostate cancer. This study will assess the safety and tolerability of PTK787/ZK 222584, and evaluate serum vascular endothelial growth factor (VEGF) levels.

This is an open-label, phase II trial of PTK787/ZK 222584. Patients will receive 750 mg daily for one week, 1000 mg daily for the second week, and then 1250 mg per day thereafter.

Response Assessment: In the absence of toxicity or clinical progression, patients will remain in the study until their PSA (Prostate-specific Antigen) has doubled from pretreatment baseline.

Inclusion Criteria:

• Histologic or cytologic diagnosis of prostate cancer
• No evidence of metastatic disease
• PSA-only progression despite androgen depravation therapy and antiandrogen withdrawal
• Patients must maintain castrate levels of testosterone (<50ng/mL) or continue on LHRH ( Luteinizing Hormone-releasing Hormone) analog therapy.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-2 (A measure of quality of life where 0 represents asymptomatic and 5 represents death)
• No prior anti-VEGF therapy is allowed
• No investigational or commercial agents or therapies other than LHRH agonists/antagonists may be administered concurrently with intent to treat the patient's malignancy
• Age greater than or equal to 18 years
• Life expectancy greater than 6 months
• Normal organ and marrow function obtained within 14 days prior to registration
• Must use adequate contraception prior to study entry and for the duration of study participation.

Exclusion Criteria:

• Patients may continue on a daily multivitamin, but all other herbal or alternative food supplements must be discontinued before registration.
• Patients must be on stable doses of bisphosphonates which have been started no less than 6 weeks prior to protocol therapy.
• Uncontrolled incurrent illness
• Patients with a "currently active" second malignancy are not eligible.
• Major surgery less than or equal to 4 weeks prior to randomization
• Prior chemotherapy less than or equal to 3 weeks prior to registration
• Prior biologic or immunotherapy less than or equal to 2 weeks prior to registration
• Prior investigational drugs of any kind less than or equal to 4 weeks prior to registration
• Patients who have had full field radiotherapy less than or equal to 4 weeks or limited field radiotherapy equal or less than 2 weeks prior to registration.
• Patients must not be on nonsteroidal antiandrogen blockade.
• Patients must have no evidence of disease on bone scan or computed tomography (CT) scan of the abdomen/pelvis.