Brief Summary: Background: In order to survive, brain tumors must have a network of blood vessels to supply it with oxygen and nutrients. The tumors produce substances that enable new blood vessels to form. Tandutinib and Bevacizumab are experimental drugs that may prevent new blood vessel formation and thereby slow or stop tumor growth in the brain. Objectives: To determine the safety and side effects of Tandutinib in combination with Bevacizumab in patients with brain tumors. To evaluate the response of brain tumors to treatment with Tandutinib and Bevacizumab. Eligibility: Patients 18 years of age and older with a malignant brain tumor for whom standard treatments (surgery, radiation and chemotherapy) are no longer effective. Design: Patients receive treatment in 4-week cycles as follows: Tandutinib by mouth twice a day every day and intravenous (through a vein) infusions of Bevacizumab over 90 minutes (or less if well tolerated) every 2 weeks. Treatment may continue for up to 1 year, and possibly longer, as long as there are no signs of tumor growth or serious treatment side effects. Patients are evaluated with magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) scans before starting treatment and then periodically to determine the response to treatment. Patients have physical and neurological examinations every 4 weeks and blood tests every 2 weeks. They complete quality of life questionnaires every 4 weeks.

Detailed Description: Background Bevacizumab is a monoclonal antibody directed against vascular- endothelial growth factor (VEGF), the major angiogenesis factor involved in high-grade glioma-mediated angiogenesis. Preclinical studies in our laboratory and others have shown potent antiglioma activity in vivo and early clinical trials of bevacizumab in combination with irinotecan and alone (National Institutes of Health (NIH) study) have demonstrated significant anti-vascular permeability and anti-glioma effects in patients with recurrent gliomas. Tandutinib (MLN518) along with bevacizumab represents an attempt to further capitalize on the concept of targeting the tumor vasculature. Tandutinib is a small molecule inhibitor of fms-like tyrosine kinase receptor-3 (FLT3), platelet derived growth factor receptor (PDGFR), and cKIT (type III receptor tyrosine kinases). It has demonstrated anti-leukemic activity in patients with relapsed and refractory acute myeloid leukemia (AML) whose blasts contain an activating internal tandem duplication mutation of FLT3. However, in this study tandutinib is being added to bevacizumab primarily for its activity against the PDGFR and cKIT. Hannahan and colleagues have demonstrated the additional anti-tumor activity that results in vivo with combined inhibition of the vascular endothelial growth factor receptor (VEGFR) and PDGFR. The activity of PDGFR inhibition is hypothesized to result from its effect on pericytes, the cells that surround and support endothelial cells. These cells have abundant expression of PDGFR and require platelet-derived growth factor (PDGF)-PDGFR interaction for their normal function. Objectives To establish data regarding the anti-tumor activity of the combination of bevacizumab and tandutinib in patients with recurrent high-grade gliomas, as determined by progression-free-survival. Eligibility Patients with histologically proven recurrent malignant glioma are eligible for this study. Design Patients will receive tandutinib as a single agent at a daily dose of 500 mg PO bid for the first 14 days of treatment. Radiology: Prior to the first dose of tandutinib patients will undergo an MRI-perfusion scan and an FDG-PET scan. An MRI-perfusion scan will then be repeated between days 12-14 of the first 14 days of tandutinib monotherapy. On day 15, treatment with bevacizumab will be added to the ongoing treatment with tandutinib. Bevacizumab will be given intravenously in a dose of 10 mg/kg, repeated once every 2 weeks. After completion of the first 4 weeks of combined tandutinib and bevacizumab therapy (6 weeks after initiating treatment with tandutinib) considered the first cycle of therapy) the MRI-perfusion and fludeoxyglucose 18F-positron emission tomography (FDG-PET) scans will be repeated before the next dose of bevacizumab is given. Patients who are clinically/neurologically stable, and who have radiographically stable or responding disease at the end of that first cycle and every cycle thereafter (every 4 weeks), will continue treatment with tandutinib and bevacizumab. Magnetic resonance imaging (MRI)-perfusion scans will be repeated after the completion of every 4 weeks of therapy. A total of 80 patients will be enrolled to this study (GBM (glioblastoma multiforme)=40, AG=40)