• Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  

• Progression-free survival and radiologic response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Incidence and severity of CNS hemorrhage and systemic hemorrhage. Incidence of grade > 4 hematologic and > grade 3 non-hematologic toxicities [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  

Drug: Avastin, radiation, temozolomide, and irinotecan

Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other wk. begin minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury.

Follow completion of XRT, pts. will have MRI and if there is no evidence of disease progression will receive 6 cycles of Avastin, temozolomide, and irinotecan. Begin min. of 14 days after last XRT, Avastin at a dose of 10 mg/kg in comb. with irinotecan every other wk.; temozolomide will be given at 200 mg/m2/day 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is on an enzyme-inducing antiepileptic drug (EIAED). If the patient is on an EIAED, the patient will receive 340 mg/m2 every other wk. If the pt. is not on an EIAED, the dose of irinotecan will be 125 mg/m2. The treatment will continue for 6 cycles. After 6 cycles, if MRI or PET show residual enhancement, the pt. may continue.

The standard of care for grade IV gliomas is radiation therapy with daily temozolomide, followed by 6 months of temozolomide. The majority of patients progress and die of their tumor. Many glioma patients are resistant to temozolomide because the tumors have high MGMT, conferring resistance. Irinotecan is synergistic with temozolomide, and the combination may overcome high MGMT. Vascular endothelial growth factor (VEGF) is present on the cell surface and around malignant gliomas. It appears that the presence of vascular endothelial growth factor is a prognostic growth factor with more VEGF expression correlating with a poor prognosis. Monoclonal antibodies to VEGF have inhibited growth of malignant gliomas in a mouse xenograft. Avastin is a humanized monoclonal IGG 1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor. The combination of Avastin and irinotecan was safe and demonstrated high activity against recurrent malignant gliomas. The combination of Avastin, temozolomide, and irinotecan as the initial therapy may maximize the chance for long-term survival. There are other studies completed or ongoing for newly diagnosed GBM patients, including a RTOG study that added irinotecan to temozolomide following standard radiation therapy and temozolomide, and a UCLA study that added Avastin to standard radiation therapy and temozolomide followed by Avastin and temozolomide.