2000 Background: Bevacizumab (BV) is a humanized monoclonal antibody directed against the vascular endothelial growth factor (VEGF). Based on the promising activity of BV in the treatment of recurrent glioblastoma, we are conducting a phase II trial to determine whether up-front treatment of newly diagnosed GBM with BV may be more advantageous than withholding BV until recurrence. In this trial, we evaluate the safety and efficacy of BV combined with standard of care radiation (RT) and temozolomide (TMZ) and radiation (RT) for newly-diagnosed GBM. Methods: This is a phase II trial with a 10-patient pilot and 60-patient expansion phases. Newly-diagnosed GBM patients with no prior treatments are eligible. Primary outcome measure is overall survival; the secondary outcome measure is TTP and 12-month survival. Therapy began between 3–5 weeks of surgery with BV (10 mg/kg every 2 weeks), TMZ (75 mg/m2 daily), and external beam RT (30 x 200 Gy) on the same day. After completion of radiation, patients are then placed on a maintenance phase of BV (10mg/kg every 2 weeks) and TMZ (150–200 mg/m2 5 out of every 28 days) until progression or 24 months in which patients are then maintained on BV only. Results: 70 of 70 projected GBM patients have been enrolled between August 2006 and November 2008 at UCLA and Kaiser Permanente (KP) (Northern and Southern California). All patients had resections to ensure that frozen tissue (>200mg) was collected. The median age was 57.4 years (range 31–75). MGMT methylation analysis has been performed on 52/70 patients with ∼40% showing methylation. Severe adverse events to date have included ischemic stroke, pulmonary embolus, wound breakdown, GI bleeding/perforation, and renal dysfunction. Isolated cases of retinal detachment and optic neuropathy have also been observed. As of now, 35/70 patients are off study (26 due to progression and 9 due to SAE). Preliminary TTP by Kaplan-Meier analysis is promising compared to that of a UCLA/KP control group of patients that received the conventional RT/TMZ regimen. Conclusions: Addition of BV to the standard regimen of TMZ and RT for newly-diagnosed GBM is well-tolerated and shows promising efficacy. More detailed analysis of safety and efficacy will presented. [Table: see text]

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