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.
ASJC Scopus subject areas
- Cancer Research