Arizona: CPI-613 trial (alpha lipoic analog)

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Phase 1 update: http://www.asco.org/ASCOv2/Meetings/...stractID=43689



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

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Sub-category:
Phase I Studies

Category:
Developmental Therapeutics - Clinical Pharmacology and Immunotherapy

Meeting:
2010 ASCO Annual Meeting

Session Type and Session Title:
This abstract will not be presented at the 2010 ASCO Annual Meeting but has been published in conjunction with the meeting.

Abstract No:
e13136

Citation:
J Clin Oncol 28, 2010 (suppl; abstr e13136)

Author(s):
A. S. Retter, R. Shorr, R. Rodriguez, K. Hoffman, F. Volterra, A. D. Hoffman, N. Huppert, K. Lee; Eastchester Center for Cancer Care, Bronx, NY; Cornerstone Pharmaceuticals, Cranbury, NJ
Abstract:
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 validated Liquid Chromatography-Mass Spectroscopy method. Results: 9 patients have been treated to date and accrual is ongoing. No DLT has been seen through the first 3 cohorts. The only AE grade 3 or higher were hematologic and attributable to (G). MTD has not yet been reached. PK studies show that plasma (C) levels are appropriately dose-related and plasma half-life was approx 2-6 hours. Response assessments for 8 patients in the first 3 cohorts show 4 pts (tumor types breast and colon) with stable disease that ranged from 4 to 16 weeks in duration. PET imaging showed a reduction from 4-42% as well in FDG avidity. Conclusions: CPI-613 in combination with (G) appears to be well-tolerated with promising efficacy in patients with solid tumors.