Abstract #3606: Azixa, a microtubule formation inhibitor in solid tumors: results of a phase 1 clinical trial

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO Purpose: Azixa\#8482; (MPC-6827) (4-arylaminoquinazolines) is a small molecule inhibitor of microtubule formation, which exerts its actions via binding to the same or nearby site as colchicine on \#946;-tubulin. We determined the dose-limiting toxicity (DLT) and maximum tolerated dose of Azixa\#8482; in patients with solid tumors. Experimental Design: Patients with advanced or metastatic cancer were treated with a 2-hour intravenous (IV) infusion once weekly for 3 consecutive weeks. Cycles were repeated every 28 days. The starting dose was escalated as follows: 0.3, 0.6, 1.0, 1.5, with subsequent increments of 0.6 mg/m² until the maximum tolerated dose 3.3 mg/m2 was reached. A conventional \#8220;3 + 3\#8221; design was used. Responses were assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). Results: Forty-eight patients (median age, 56; median number of prior therapies, 4) with advanced solid tumors received therapy; and 93 cycles were administered (median 1; range, 1-10). Toxicities reported to be study drug-related include Grade 3 allergic reaction (n=1) and Grade 3 confusion (n=1) at 1.5 mg/m2, Grade 3 arrhythmia (n=1) at 3.3 mg/m2, and Grade 3 myocardial infarction at 3.9 mg/m2 (n=1) and 4.5 mg/m2 (n=1). Thirty-five patients (73%) reported no greater than Grade 1 drug-related toxicities. No drug-related DLTs were reported with azixa dose levels ranging from 0.3 to 3.3 mg/m2. Five (10.4 %) of the 48 patients achieved stable disease by RECIST for \#8805; 4 months (median = 5, range = 4-10). These patients had received 2 to 11 prior therapies and they had the following diagnoses: breast cancer, parathyroid cancer, carcinoid of the rectum, thymoma, and endometrial cancer. Conclusions : The maximum tolerated dose of Azixa\#8482; was determined to be 3.3 mg/m2 IV administered over 2 hours once weekly for 3 consecutive weeks every 4 weeks. Axiza therapy resulted in disease stabilization for \#8805; 4 months in 5 patients with heavily pretreated advanced cancer. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3606.