The overall goals of this grant application are to develop innovative phase I and phase II trials of new and promising agents or therapeutic approaches for primary malignant CNS tumors, and to provide a carefully maintained database of clinical trials results. MDACC will be part of the National Central Nervous System Consortium (NCNSC) of five clinical centers with the Central Operation Office/Coordinating Center located at MDACC. Some of the hypotheses, based on our own research interest, that we will test, with respect to specific clinical therapies, are: a) Combination of some biological and cytotoxic chemotherapeutic agents that show synergistic activity in cell culture may be active in patients with primary malignant brain tumors. b) New polyamine inhibitors will decrease tumor growth by interfering with polyamine synthetic pathways. c) Growth factors/cytokines and their receptors that are associated with brain tumors can be potential therapeutic targets for antisense approaches. d) Antiangiogenesis agents will inhibit tumor growth and/or invasion by suppression of new tumor vessel formation. Based on these hypotheses, our specific aims are to 1) Treat malignant cerebral gliomas at progression or recurrence with new phase II agents and innovative combinations of biological and chemotherapeutic agents. This forms the basis for our first consortium protocol studying the efficacy of a new recombinant interferon-beta molecule alone and in combination with cis-retinoic acid in patients with recurrent malignant gliomas; 2) Develop phase I or II trials with newly synthesized cytotoxic agents, polyamine inhibitors and antiangiogenesis agents as they become available; 3) Collaborate with other member clinical centers within the consortium to develop clinical trials of retroviral vectors or antisense approaches transferring knowledge learned in the laboratory to the clinic. 4) Continue laboratory modeling of antisense approaches against oncogene encoded growth factors/cytokines and their receptors with the aim of bring these approaches to clinical trials by the consortium. 5) Maintain a patient data base on all patients with brain tumors including relevant clinical and laboratory data using the Protocol Data Management System (PDMS) software available at the MDACC.
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