TRC105 for Recurrent Glioblastoma

Background: * TRC105 is an anti-angiogenic monoclonal antibody (mAb) that binds to CD105 (Endoglin), a transmembrane glycoprotein that is essential for angiogenesis, and expressed abundantly on activated vascular endothelial cells (ECs). CD105 is a member of the transforming growth factor-Beta (TGF-Beta) receptor superfamily, and modulates TGF-Beta signaling leading to EC proliferation and migration. * Immunohistochemistry studies reveal that CD105 is preferentially expressed in blood vessels of tumor tissues as compared with normal mucosa. For patients with glioblastoma multiforme (GBM), increased expression of CD105 may correspond to worse survival times. Furthermore, expression of CD105 is essential for neovascularization, and is upregulated in the setting of (vascular endothelial growth factor ) VEGF inhibition. * TRC105 binding to CD105 leads to inhibition of EC proliferation, neovascularization, and induces cell death via apoptosis. TRC105 may also mediate antibody-dependent cellular cytotoxicity (ADCC). Objectives: Primary * To determine the radiographic response rate for patients with recurrent GBM treated with TRC105. * To establish data regarding the anti-tumor activity of TRC105 in patients with GBM, as determined by progression free survival. Secondary * To obtain information regarding the safety of TRC105 in patients with recurrent GBM. * To evaluate the health-related quality of life (HRQL) in patients while on treatment with TRC105. * To examine the effect of TRC105 on vascular permeability as measured by percent change from baseline in the forward contrast transfer rate (Ktrans) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). * To examine the effect of TRC105 on vascular perfusion as measured by percent change from baseline in cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) of dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). * To examine the effect of TRC105 on water diffusion as measured by percent change from baseline in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of diffusion magnetic resonance imaging (MRI). * To examine the effect of TRC105 on tumor metabolism as measured by percent change from baseline in fludeoxyglucose F18 injection (FDG) uptake of positron emission tomography (PET) scan. * To obtain preliminary data regarding how changes in serial FDG-PET scans and physiological MRI correlate with radiographic response rates and with progression free survival in patients treated with TRC105. Eligibility: -This is a phase II trial in patients with recurrent GBM who are VEGF therapy naive. Design: -Prior to treatment start, patients will undergo a magnetic resonance imaging (MRI) including MRI perfusion and diffusion scans, as well as an FDG-PET scan. Patients will then receive TRC105 as a single agent (weekly dose of 10 mg/kg IV). A cycle will consist of 4 weeks of therapy. At the end of the first cycle, the magnetic resonance (MR) imaging and FDG-PET scans will be repeated before continuing treatment. Patients who are clinically and neurologically stable, and who have radiographic stable or responding disease at the end of each cycle will continue treatment with TRC105. MRI perfusion and diffusion will be repeated after the completion of each cycle of therapy.