A phase I dose-escalation study of weekly multiple dose intravenously administered SR271425 in patients with refractory solid tumors

3095 Background: The thioxanthone analog, SR271425, is a novel cytotoxic DNA-interacting agent with a broad spectrum of antitumor activity in preclinical murine tumor models. This clinical trial aims to determine tolerability and toxicities of SR271425 as a 1-hour single intravenous dose repeated weekly for 2 weeks followed by 1 week rest, to determine the maximum tolerated dose (MTD), recommended phase II dose (RPIID), and to assess its pharmacokinetic profile. Methods: A modified Fibonacci dose escalation design is being used. A single intravenous dose of SR271425 is administered over 1-hour weekly for 2 weeks, followed by 1 week rest, in a variety of refractory solid tumors. Of note, in the rabbit model, QTc prolongation, related to Cmax, has been reported at doses >660mg/m2. Therefore, all patients are undergoing cardiology assessment with serial ECGs, which are assessed by a central reviewer. Results: To date, 17 patients have been treated at 5 dose levels (ranges, 64–675 mg/m2/week). The mean age is...