A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK 222584 or placebo (CONFIRM-1)

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Abstract
LBA3 Background: PTK787/ZK 222584 (PTK/ZK) is a novel, oral, small molecule, anti-angiogenesis compound that blocks tyrosine kinase signaling from all known vascular endothelial growth factor (VEGF) receptors. Phase I/II studies of PTK/ZK as a single agent showed that it is safe and well tolerated. Dose response was observed by DCE-MRI. An expanded phase I/II study evaluating escalating doses of PTK/ZK in combination with oxaliplatin/5-FU/LV as first-line therapy of metastatic colorectal cancer (CRC) demonstrated that chemotherapy and PTK/ZK could be safely administered as combination therapy. An overall response rate of 49% was observed; an additional 44% of Pts achieved stable disease. Methods: A multinational, randomized double-blind, placebo controlled phase III study has recently been completed to evaluate PTK/ZK in combination with the FOLFOX-4 regimen (oxaliplatin/5-FU/LV) in Pts with metastatic adenocarcinoma of the colon or rectum. Pts were included if they had histologically documented metastatic CRC, the presence of measurable disease, WHO Performance Status of 0–2 and adequate organ and bone marrow function. Pts were stratified in a 1:1 randomization scheme to receive oxaliplatin/5-FU/LV every 2 weeks according to the FOLFOX-4 regimen (de Gramont 2000) with either placebo or PTK/ZK given at a dose of 1250 mg, administered on a once-daily continuous schedule. Adjuvant therapy for primary CRC was acceptable providing that at least 6 months had elapsed from the conclusion of therapy to the time disease recurrence was documented. The primary endpoint was progression free survival (PFS). The study was designed to have at least 90% power to detect an increase in median PFS from approximately 9 months to 12 months at 5% significance level (two-sided). PFS data for the two treatment arms will be compared using a stratified log-rank test. Results: A total of 1168 Pts were randomized. Data for the primary endpoint (PFS) and secondary endpoints (overall response rate, time to progression, safety) will be presented for both treatment groups.

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