Vandetanib Plus Mfolfox6 In Patients With Advanced Colorectal Cancer (Crc): A Randomized, Double-Blind, Placebo-Controlled Phase Ii Study

4084 Background: Vandetanib is a once-daily oral agent that selectively targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. Methods: Eligible patients with advanced CRC and who had previously progressed after an irinotecan- and fluoropyrimidine-containing regimen were randomized 1:1:1 to receive once-daily oral vandetanib (100 or 300 mg) + modified FOLFOX6 (mFOLFOX6) or placebo + mFOLFOX6; mFOLFOX6 was given as standard 14-day treatment cycles (oxaliplatin 85 mg/m2 2-hr and leucovorin 400 mg/m2 2-hr i.v. infusions, followed by 5- fluorouracil [5-FU] 400 mg/mg2 i.v. bolus and 5-FU 2400 mg/m2 46-hr i.v. infusion). The primary objective was to compare the number of patients with a progression event on or before a mandatory tumor assessment visit at data cut-off (∼4 months after last patient randomized). A progression event was defined as the earliest of objective and/or clinical disease progression, or death from any cause. Results: Between March and November 2007, 104 patients (aged 32–81 years) were randomized to receive study treatment ( Table ). At data cut-off on 8 March 2008, there was a greater % of progression events in the vandetanib 100 mg arm compared with placebo (72% [n=23] versus 65% [n=24]; HR=1.21, 2-sided 80% CI 0.82–1.80; 2-sided P=0.53), and also in the vandetanib 300 mg arm compared with placebo (77% [n=27] versus 65% [n=24]; HR=1.41, 2-sided 80% CI 0.96–2.07; 2-sided P=0.25). All except one patient in each group experienced an adverse event (AE) during the study with diarrhea, nausea, thrombocytopenia, and peripheral sensory neuropathy the most commonly reported AEs ( Table ). Neutropenia was the only CTC grade 4 AE to occur in >1 patient in any group (n=2, vandetanib 100 mg arm; n=0, vandetanib 300 mg arm; n=3, placebo arm). Conclusions: In this study of patients with advanced, previously treated CRC, there was no efficacy benefit for vandetanib (100 or 300 mg) + mFOLFOX6 versus placebo + mFOLFOX6. [Table: see text] [Table: see text]