Phase I clinical trial of MPC-6827 (Azixa), a microtubule destabilizing agent, in patients with advanced cancer

Apostolia Maria Tsimberidou, Wallace Akerley, Matthias C. Schabel, David S. Hong, Cynthia Uehara, Anil Chhabra, Terri Warren, Gary G. Mather, Brent A. Evans, Deane P. Woodland, Edward A. Swabb, Razelle Kurzrock

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

MPC-6827 (Azixa) is a small-molecule microtubule-destabilizing agent that binds to the same(or nearby) sites on β-tubulin as colchicine. This phase I study was designed to determine the dose-limiting toxicities (DLT), maximumtolerated dose(MTD), and pharmacokinetics (PK) ofMPC-6827 in patients with solid tumors. Patients with advanced/metastatic cancer were treated with once-weekly, 1- to 2-hour intravenous administration of MPC-6827 for 3 consecutive weeks every 28 days (1 cycle). Dose escalation began with 0.3, 0.6, 1, and 1.5mg/m2, with subsequent increments of 0.6 mg/m2 until the MTD was determined. A 3 + 3 design was used. Pharmacokinetics ofMPC-6827 and itsmetaboliteMPI-0440627 were evaluated. Forty-eight patients received therapy; 79 cycleswere completed(median, 1; range, 1-10). Themost common adverse eventswere nausea, fatigue, flushing, and hyperglycemia. The DLT was nonfatal grade 3 myocardial infarction at 3.9 mg/m2 (1/6 patients) and at 4.5mg/m2 (1/7 patients).TheMTDwas determined to be 3.3mg/m2 (0/13 patients had aDLT). Five (10.4%) of the 48 patients achieved stable disease (Response Evaluation Criteria in Solid Tumors) for 4 months or greater. MPC-6827 has a high volume of distribution and clearance. Half-life ranged from 3.8 to 7.5 hours. In conclusion, MPC-6827 administered intravenously over 2 hours at a dose of 3.3mg/m2 onceweekly for 3weeks every 28days was safe in patients with heavily pretreatedcancer. Clinical trials withMPC-6827 and chemotherapy are ongoing.

Original languageEnglish (US)
Pages (from-to)3410-3419
Number of pages10
JournalMolecular cancer therapeutics
Volume9
Issue number12
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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