sNDA#20-637GLIADELWAFER(Polifeprosan20with分析.pptVIP

sNDA # 20-637GLIADEL? WAFER(Polifeprosan 20 with Carmustine Implant)APPLICANT: GUILFORD PHARMACEUTICALS ODAC: December 6, 2001 Medical Reviewer: Alla Shapiro, M.D., Ph.D. Statistical Reviewer: Ning Li, M.D., Ph.D. FDA Presentation Regulatory history Dr. Alison Martin Study T-301 Dr. Alla Shapiro Dr. Ning Li Review Issues Dr. Alison Martin Regulatory History  Approved June 14, 1996 Indication: Adjunct to surgery to prolong survival in patients with recurrent GBM for whom surgical resection is indicated Regulatory History Primary Basis of Approval North American trial, #8802 multicenter, randomized, placebo-controlled 22 pts with recurrent malignant glioma subgroup analysis in GBM: ? OS and 6 mo. survival Supportive: Scandinavian trial, #CL-0190 early closure (32/100); randomization imbalance not sufficient to support a new indication New Indication Meeting with FDA 1/30/97 Single trial can support a new indication if... multicenter results are robust Population of interest: GBM Placebo wafer accepted Standardization of subsequent treatments Prospective definition and collection of AEs New Indication Sample size (90% power): based on 12 month survival rate for Gliadel of 70% vs. 50% FDA 8/22/97: overly optimistic if 62.5% vs. 50%, 53% power Amendment 3/18/99: IDMC review of blinded data: overly optimistic accrual ? from 200 to 240 preserve ability to distinguish 68% vs. 50% Clinical ReviewStudy T-301 GLIADEL Wafer Proposed Indication “GLIADEL Wafer is indicated for use as a treatment to significantly prolong survival and maintain overall function (as measured by preservation of Karnofsky Performance Status) and neurological function in patients with malignant glioma undergoing primary and/or recurrent surgical resection”. Study Objectives Primary - survival (ITT) Secondary - survival in the GBM subgroup -adjusted analyses for KPS, age and tumor type -1-year survival (ITT and GBM) - progre