) This proposal is being submitted as part of a cooperative agreement with other members of the New Approaches to Brain Tumor Therapy (NABTT) Consortium (Project Leaders: Henry Brem, M.D. and Stewart Grossman, M.D.; Coordinating Center, Johns Hopkins University), in order to design and conduct Phase I and Phase II treatment protocols for patients with anaplastic gliomas. The primary objective of this proposal is to improve the outcome for adult patients with primary brain tumors. We propose to address this goal by combining our clinical investigative strengths with those of the other members of the NABTT Consortium (Brown University, Columbia University, Emory University, H. Lee Moffitt Cancer Center, Henry Ford Hospital, Johns Hopkins University, Massachusetts General Hospital, Northwestern University, Wake Forest University, Washington University, University of Alabama at Birmingham, University of Pennsylvania, and University of Texas at San Antonio). The particular strengths that our institution brings to the NABTT Consortium include: 1) a large number of patients with primary brain tumors and a well-developed referral network, 2) a brain tumor-dedicated multidisciplinary clinical team that has been in place for over ten years, 3) extensive clinical and laboratory resources, 4) a significant number of NIH-supported brain tumor laboratory research programs, including a recently-awarded Brain Tumor Program P r oject Grant (P01 NS34856, Steven Rosenfeld, M.D., Ph.D., Principal Investigator), as well as a number of industrial-academia contacts for support of neuro-oncology research on campus, and 5) nationally-recognized expertise in cancer research, including biostatistics and data management, in the clinical pharmacology of cancer therapeutics, in functional neuroimaging, and in the conducting of institutional and cooperative Phase I and II clinical trials. This proposal thus builds on our extensive clinical investigative expertise within the context of a well established multi-institutional brain tumor treatment consortium.