Phase I trial of CPI-613, a lipoic acid analog, and gemcitabine in patients with advanced solid tumors.

e13136 Background: Lipoic acid analogs are a novel class of anticancer agents that target the altered form of pyruvate dehydrogenase (PD) and possibly α-ketoglutarate dehydrogenase (KDH) causing a significant inhibition of mitochondrial energy metabolism selectively in tumor cells, leading to apoptosis. CPI-613 (C), a member of this novel class, has shown excellent toxicity and efficacy profiles in preclinical models. We initiated a phase I dose-escalation study utilizing the combination of (C) and gemcitabine (G) in patients with metastatic solid tumors. Methods: Patients were treated with (G) 1000 mg/m2 on days 1, 8, and 15 and (C) at escalating doses on days 1, 4, 8, 11, 15 and 18 of a 21-day cycle. Three cohorts of patients each with 3 patients received (C) at a dose of 21, 42, and 70 mg/m2 respectively. Intrapatient dose escalation was allowed and patients received from 1 to 5 cycles of treatment. Tumor types included breast, colon, and pancreas. Plasma concentrations of (C) were assayed using a vali...