The focus of this grant application is a proposal to conduct phase I and II investigational drug trials in adult patients with anaplastic gliomas in the context of a multi-institutional consortium. The ultimate purpose of these phase I and II trials is to identify agents with sufficient activity to justify definitive phase III testing in adults with anaplastic gliomas. In general, these phase III trials will be conducted by the consortium or a sub-group of the consortium. Patients at the University of Texas Southwestern Medical Center (UTSW) will be evaluated and treated by a multidisciplinary team composed of neuro-oncologists, medical oncologists, neurosurgeons, radiation oncologists, neuropathologists, neuroradiologists, and clinical research nurses. Clinical data on all CNS tumor patients are collected and stored locally and will be transmitted to the Central Operations Office and Data Coordinating Center of the consortium at the University of California at San Francisco. Agents to be tested in the Phase I and II trials will be selected in the context of semiannual recommendations and preferences, b) pre-clinical experimental data from participant consortium institutions (including particularly the athymic mouse screening system in place at UTSW and the stem cell assay used in the consortium pharmacology center at San Antonio), and c) knowledge of the current literature and frequent interchanges about prioritizing potential new agents. The first 2 phase II agents to be tested by this consortium will be taxol and temozolomide. In addition, tissue from all resected gliomas (and other CNS neoplasms) is banked in an existing system at UTSW and will be shared with other consortium members. Serum samples from protocols patients will be supplied to the consortium pharmacology center in San Antonio for pharmacokinetic studies of the agents to be tested. The consortium estimates accrual of a minimum of 140 patients per year on phase I and II studies (at least 20/year at each of 7 clinical centers), allowing us to evaluate at least 4 agents per year. Detailed pharmacokinetic studies will be performed on 2 of these agents each year.
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