A Phase II Study of Gliadel, Concomitant Temozolomide and Radiation, Followed by Metronomic Therapy With Temozolomide for Newly Diagnosed Malignant High Grade Glioma

Inclusion Criteria:

- Men and women, must be between ages 18-72

- Patients must have radiographic evidence on cranial magnetic resonance imaging (MRI)
of a single, contrast-enhancing unilateral supratentorial cerebral tumor suggestive
of high-grade glioma

- Surgical treatment within 4 weeks of the baseline MRI is indicated

- Karnofsky Performance Score of 60 or higher

- Patients must have a pathological diagnosis of high-grade (IV) malignant glioma

- Patients must be willing to use a barrier method of contraception if fertile or if of
childbearing potential for up to 2 years after wafer implantation and be counseled
regarding the unknown, and potentially harmful, risks to the embryo or fetus while
treated on this study

Exclusion Criteria:

- Patients who have had prior cytoreductive surgery for high-grade glioma (patients who
have had a diagnostic stereotactic biopsy are eligible)

- Patients 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 patient could
reasonably be expected to die within the first 12 months of the study

- Known hypersensitivity reactions to temozolomide, nitrosoureas or any components of
the Gliadel wafer

- Prior CNS radiotherapy

- Patients who have received any prior chemotherapy for malignant glioma prior to the
baseline evaluation or patients who are currently being treated with chemotherapeutic
agents

- Patients 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 employing
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