Clinicians and clinical investigators, along with their scientist colleagues, are looking for more effective and safer ways to treat brain tumors. When laboratory research shows us that a new treatment has promise, clinical investigators and clinicians test the new treatment in well-controlled and closely scrutinized treatment protocols called clinical trials. These trials are designed to answer two basic questions: Is this treatment safe? (usually Phase I trials) Is this treatment effective? (usually Phase II trials) By taking part in a clinical trial, patients make an important contribution to medical research and science. They may also benefit from treatments that usually are not available outside a clinical trial. Many different types of clinical trials are available including those using: Radiation therapy New anticancer drugs New drug combinations Immunotherapy The NeuroOncology Branch (NOB) at the National Institutes of Health (NIH) is a team of dedicated medical professionals and scientists working to develop new therapies for patients with primary brain and spinal cord tumors. NOB is a joint program of the National Cancer Institute (NCI) and the National Institute of Neurological Disorders and Stroke (NINDS). In 1999, NCI saw approximately 10 primary brain tumor patients per year. We now see more than 200 new primary brain tumor patients per year and more than 2,000 follow up patients per year. This expansion in patient numbers was enabled by the rigorous and ambitious building of a primary neurooncology clinical care/research team, and establishing an NIH-wide multidisciplinary Brain Tumor Clinic with active participation from various NCI Branches, NIH Institutes, and Clinical Center Programs (neuroradiology, neurosurgery, radiation oncology, laboratory pathology, rehabilitation medicine, social work, tumor immunology). Through extensive collaborations established with the pharmaceutical and biotechnology industry, as well as through the translational science being generated in the NOB laboratory, we have been able to create and activate more than 40 clinical trials within NOB. This large clinical patient population and large number of available clinical trials allow us to accrue between 200 to 250 glioma patients per year to clinical trials. Our current portfolio of investigations include novel agents that are considered molecularly targeted treatments and/or antiangiogenic strategies to treat resistant malignant gliomas. Some compounds are in very early stages of development being tested in the phase I setting to identify toxicities and describe the pharmacokinetics of the drug. Other regimens are being tested in the phase II setting to evaluate whether there is any signal of efficacy and to further define treamtent related side effects. We also are exploring immunotherapy approaches to brain tumors using peptide vaccine and adoptive immunotherapy treatments. One of these efforts is through a collaboration with our partners in the Tumor Immunology group of the Surgical Oncology Branch. A number of studies also include correlative investigations of tissue and imaging biomarkers for drug activity in the brain and body.