Phase II Study of Verubulin (Azixa, MPC-6827) with Radiation Therapy and Temozolomide in Newly Diagnosed Glioblastoma Multiforme Patients: Incomplete Report on Safety, Tolerability and Responses (P3.125)

OBJECTIVE: To establish safety, tolerability and efficacy of Azixa when combined with standard of care therapy (SOC) (RT/TMZ) in newly diagnosed GBM patients. Such combination may improve survival of patients with newly diagnosed GBM. BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumors with a median overall survival of 14.6 months despite surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Anti-angiogenesis therapy, bevacizumab (BV), has emerged as a treatment option for progressive GBM. Azixa is a novel microtubule destabilizer and functions as a potent cytotoxin and a vascular disrupting agent. It evades multidrug resistance pumps and achieves high CNS concentrations. It is potently active in multiple xenograft models. Phase I data had determined MTD at 3.3 mg/m 2 and showed no significant toxicity. A phase II study of Azixa for recurrent GBM with or without BV had demonstrated no significant adverse effect either. DESIGN/METHODS: Part A is an open-label standard 3+3 dose finding design to establish the MTD of Azixa (doses 2.2, 3.3 or 2.8 mg/m 2 ) with SOC. Part B was planned as an open-label, randomized, 2-arm, comparative trial. Part A consists of SOC with Azixa (weekly for 5 weeks out of 6 weeks period) followed by a 28-day break, then six cycles of TMZ (5 days on/23 days off/cycle) with Azixa (weekly for 3 weeks/cycle) for a total of 6 cycles. Primary endpoints are safety, tolerability and 9-month progression-free survival (PFS-9). RESULTS: The trial was terminated in March, 2012 by the sponsor for financial reason. Incomplete data demonstrated that Azixa is well tolerated and it is safe to use with SOC. Three patients are long term survivors over 3 years. One of them is still alive without evidence of disease. CONCLUSIONS: Azixa is well tolerated and it warrants further investigaiton. Study Supported by: Myrexis, Inc. Disclosure: Dr. Zhu has received personal compensation for activities with Novocure and Prime Oncology. Dr. Kesari has received personal compensation for activities with Enzon Pharmaceuticals, Bristol-Myers Squibb Company and Genentech, Inc. as a speaker and/or advisory board member. Dr. Recht has received personal compensation for activities with Pharmacyclics, Inc.