PRE-IRRADIATION 9-AMINO-20(S)-CAMPTOTHECIN IN GLIOBLASTO

University Of Pennsylvania, Philadelphia PA

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Linked publications & trials

Abstract

9-AC, an analogue of the topoisomerase I inhibitor, camptothecin (CPT), has demonstrated activity in vitro and in vivo. Topoisomerase I relaxes supercoiled DNA by nicking a strand in order to prepare the DNA template for further synthesis. The primary objective of this study is to estimate the response rate of recurrent malignant glioma treated with 9-AC administered as a 72-hour infusion every 2 weeks for 6 courses. The objective for the initial Phase II component is to determine if the initial dose/schedule is optimal for this patient population with patients stratified between two groups according to anticonvulsant usage. The Phase I component of this study aims to determine the maximum tolerated dose (MTD) for patients in Group A (anticonvulsants) and Group B (non-anticonvulsants). Once the MTD is determined the subsequent Phase II component will examine the efficacy and effectiveness of that dosage by estimating the response rate to 9-AC administered as a 72-hour infusion; determining the time to progression, seeking correlations between steady state 9-AC levels and 9-AC clearance with toxicity and/or drug activities; and determining the toxicity of chemotherapy with 9-AC in adults with recurrent or progressive malignant glioma.