Phase I trial of TPI 287 as a single agent and in combination with temozolomide (TMZ) in patients with refractory or recurrent neuroblastoma (NB) or medulloblastoma (MB).

Abstract

9554 Background: Survival for children diagnosed with NB after age 18 months is <40% despite aggressive multimodal therapy. Similarly, <15% survive relapse of MB, with often severe long-term toxicity. A novel anti-microtubule agent, TPI 287, has very high potency against several NB and MB cell lines and xenograft models, prompting a phase I study to determine the safety, tolerability and maximum tolerated dose (MTD) of TPI 287 in patients with refractory or recurrent NB or MB. Secondary objectives were to evaluate the pharmacokinetics (PK) and anti-tumor activity of TPI 287 in these patient populations, both as a single agent and in combination with temozolomide. Methods: Patients with relapsed or refractory NB or MB were enrolled in a multicenter, dose escalation 3+3 design study and received intravenous TPI 287 on days 1, 8 and 15 of each 28-day cycle. After 2 cycles, TMZ 100 mg/m2 was added on days 1-5 of each cycle. The MTD of single agent TPI 287 was the dose below which DLTs were seen in ≥ 2 of 6 pa...