The application indicates the intellectual energy and resources at St. Jude Children's Research Hospital that will be committed to the Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC). The institutional Neurobiology and Brain Tumor Program represents a talented group of experienced clinical and laboratory investigators (including 22 MD's, PhD's, and PharmD's) with particular expertise in pediatric neuro-oncology, radiation oncology, neurosurgery, molecular pharmacology, pharmacokinetics, neuroimaging, neuropsychology, and biostatistics. The Program accrues an average of 75 newly diagnosed children with brain tumors annually, and is just now positioned to increase accession to phase I and II studies for children with previously treated disease. Amongst the 258 children entered on institutional brain tumor protocols since 1990, significant contributions have been made in medulloblastomas, infant brain tumors, low grade gliomas, and malignant gliomas. During the interval, 154 children have been entered on POG studies, many of which reflect administrative and scientific leadership from St. Jude. Recent protocols highlight collaborations with 2-4 additional institutions to study novel chemotherapeutic and radiotherapeutic interventions, largely derived from laboratory investigation at St. Jude, in medulloblastoma, infant brain tumors, and low grade gliomas/ependymomas. The linear development of protocols (based upon preclinical in vitro and xenograft models, detailed pharmacokinetic studies, and ongoing development of improved means of evaluating tumor response and toxicities) indicates the integration of scientific research and clinical trial design and management that offers considerable expertise as the Program fully commits its resources to the PBTCTC. The development of correlative laboratory studies, including genetic analyses and explorations using the new Patched medulloblastoma model, and translational research evaluating alterations in the Atm gene as potential targets to alter radiation sensitivity, offer enormous potential for the identification of novel therapeutic interventions. The institutional contributions to the PBTCTC combine laboratory and clinical science with a sizable patient base that will be dedicated to consortium trials.
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