ATNT-17: EVALUATION OF THE SAFETY AND BENEFIT OF PHASE I ONCOLOGY TRIALS FOR PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM TUMORS

BACKGROUND: Patients with high-grade gliomas (HGG) are frequently excluded from first-in-human solid tumor trials (STS) due to perceived poor prognosis, excessive toxicities, concomitant drug interactions, and poor efficacy. We conducted an analysis of outcomes from select, single agent phase I studies in HGG patients. We compared outcomes to pooled analysis of published studies in STS with various molecular and cytotoxic drugs evaluated as single agents or as combinations. METHODS: Individual records of patients with recurrent HGG enrolled to Adult Brain Tumor Consortium (ABTC) trials of single agent, cytotoxic or molecular agents from 2000-2008 were analyzed for baseline characteristics, toxicities, responses and survival. RESULTS: Our analysis included 327 patients with advanced, refractory HGG who were enrolled in 8 trials involving targeted molecular (5) and cytotoxic (3) therapies. At enrollment, patients had a median Karnofsky Performance Status of 90; median age of 52 years; 62% were male, 63% had glioblastoma, and median number of prior systemic chemotherapies was 1. Baseline laboratory values were in an acceptable range to meet eligibility criteria. Patients were on study for a median of 2 cycles (<1 to 56) and 96% were evaluable for primary endpoints. During cycle 1, grade ≥ 3 non-hematologic and grade ≥ 4 hematologic toxicities were 5 % (28/565) and 0.9% (5/565), respectively and 66% of these occurred at the highest dose level. There was one death attributed to drug. Overall response rate (CR + PR) was 5.5%. Median progression-free and overall survival were 1.8 and 6 months, respectively. CONCLUSION: HGG patients who meet standard eligibility criteria may be good candidates for solid tumor phase I studies with single agent molecular or cytotoxic drugs with favorable pre-clinical rationale and pharmacokinetic properties in this population.