C-1311, a novel inhibitor of FLT3 and topoisomerase II: A phase 1 trial of a once every three week schedule in patients with advanced solid tumors

2576 Background: C-1311 (Symadex) is a lead compound in the novel class of imidazoacridinones, inhibitors of both topoisomerase II and certain receptor tyrosine kinases (RTK) including FLT3, being tested for the treatment of cancer and autoimmune diseases. This phase 1 trial assessed safety, determined the maximum tolerated dose (MTD) and recommended dose (RD) of C-1311 in patients (pts) with advanced solid tumors. Methods: Pts with tumors refractory to conventional therapy were enrolled. The dosing schedule was a 1-hr infusion daily for 5 consecutive days every 3 weeks (dx5), subsequently amended to once every 3 weeks (q3w). The maximum tolerated dose (MTD) is where 2 or more of at least 3 pts experience dose-limiting toxicity (DLT). The recommended dose (RD) is the dose level below the MTD. An expanded RD cohort of 9 pts was also evaluated. Systemic pharmacokinetics were assessed. Results: 36 pts were treated. No DLTs were observed in the first 5 single patient cohorts on a dx5 schedule at 6, 12, 24, 48...