PHASE I, PHARMACOKINETIC, PHARMACODYNAMIC TRIAL OF PTK787 AND PACLITAXEL IN C

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. " This will be a single center Phase I study which will enter patients who meet the inclusion criteria and exhibit none of the exclusion criteria listed below. We plan on studying PTK787 plus paclitaxel in patients with advanced solid tumors. The primary objectives of this study are as follows: " To evaluate the safety and tolerability of escalating doses of paclitaxel in combination with PTK787. " To evaluate the pharmacokinetics of PTK787 and paclitaxel alone and in combination from patients with cancer accrued to this study " To evaluate the pharmacodynamic activity of PTK787 and paclitaxel via radiographic changes caused by the combination utilizing C11 Carbon Monoxide PET scanning to evaluate tumor blood flow changes with therapy Patients will be enrolled sequentially into 1 of 6 cohorts and each cohort will consist of 3 to 6 patients. Six dose levels will be assessed. The dose levels of PTK787 will be 250, 500, 750, 1000, and 1250 mg administered orally every day starting on D-11. The dose levels of Paclitaxel will be 75, 85,100mg/m2 IV given on days 1, 8, and 15 every 28 days. All patients in a cohort will be evaluated for safety throughout the 28-day treatment cycle prior to enrollment of the next cohort. The study will consist of a Screening and Baseline Period, Run-in Period, Treatment Period consisting of 28 days of study drug administration. PTK787 will continue until the appearance of significant treatment-related toxicities or disease progression. Paclitaxel will be continued until progression as toxicity permits with a maximum of 6 cycles. The assessments for this study are as follows: " Treatment emergent adverse events including laboratory assessments and directed neurological " Examinations " Tumor measurements and measurements of tumor markers (if appropriate) " Pharmacokinetic assessments from whole blood sample