To determine the safety and efficacy of surgical resection with Gliadel® 3.85% wafer implantation, followed by concomitant limited field radiation therapy and temozolomide, followed by dose dense temozolomide and bevacizumab in subjects undergoing initial surgery for newly-diagnosed high grade glioma.

Inclusion Criteria:

• Subjects, men and women, must be between ages 18 and 75 years.
• Subjects must have radiographic evidence on cranial magnetic resonance imaging (MRI) of a single, contrast-enhancing unilateral supratentorial cerebral tumor.
• Surgery is recommended within 4 weeks of the baseline MRI scan.
• Subjects must have a Karnofsky Performance Score of 60 or higher.
• Subjects must have signed an Institutional Review Board (IRB)-approved informed consent prior to any non-standard of care study procedure or no later than the start of dose dense temozolomide and bevacizumab..
• Subjects must have a pathological diagnosis of a high grade (IV) malignant glioma.
• Subjects, both men and women, must be willing to avoid pregnancy for up to 2 years after wafer implantation surgery and be counseled regarding the unknown, and potentially harmful, risks to the embryo or fetus from participation in this study.

Exclusion Criteria:

• Subjects who have had prior cytoreductive surgery for high-grade glioma. Subjects who have had a diagnostic stereotactic biopsy are eligible.
• Subjects with more than one focus of tumor or tumor crossing the midline as assessed by coronal cranial MRI scan.
• Concomitant significant life-threatening disease from which the subject could reasonably be expected to die within the first 12 months of the study.
• Known hypersensitivity reactions to temozolomide, nitrosoureas or any other components of the Gliadel® wafer.
• Prior CNS radiotherapy.
• Subjects who have received any prior chemotherapy for this malignant glioma prior to the baseline evaluation or subjects who are currently being treated with chemotherapeutic agents.
• Subjects with fewer than 100,000 platelets per mm3 or fewer than 3.500 leukocytes per mm3.
• Liver function tests greater than or equal to 2.5 times the upper limit of normal (transaminases (SGOT, SGPT), total bilirubin, alkaline phosphatase).
• Serum creatinine equal to or greater than 1.5 times the upper limit of normal, blood urea nitrogen (BUN) equal to or greater than 2.5 times the upper limit of normal.
• Pregnancy, or lactating females or females of childbearing potential not using adequate contraception.
• Participation in any other investigational protocol in the prior twelve months for any type of malignancy.
• Psychological, familial, sociological or geographical conditions which do not permit adequate medical follow-up and compliance with the study protocol.
• Inadequately controlled hypertension (blood pressure systolic > 150 mmHg or diastolic > 100 mmHg).
• Unstable angina or history of myocardial infarction within six months prior to enrollment.
• Evidence of bleeding, diathesis, or coagulopathy. Chronic full-dose anticoagulation with warfarin is not permitted though subjects may be on low molecular weight heparin or fondaparinux.
• Serious non-healing wound, ulcer, or bone fracture.