Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM)
Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM)
The purpose of this study is to determine the safety and effectiveness of Gliadel wafers at
 the time of surgery, followed by the combination of radiation, Temodar, and Avastin, and then
 the combination of Avastin and Temodar, after radiation is complete, on malignant brain
 tumors.

 About six weeks after surgery, subjects will begin standard radiation therapy, a fixed dose
 of Avastin every 2 weeks, and daily Temodar for the six and a half weeks of radiation.
 Beginning 2-3 weeks after the last radiation therapy, subjects will be given the same fixed
 dose of Avastin intravenously (through the vein) every 14 days. They will also be given a
 higher dose of oral Temodar to take daily the first 5 days of each 28-day study cycle.
Inclusion Criteria:

 -  Patients must have a MRI consistent with a WHO grade IV primary malignant glioma
 (glioblastoma multiforme or gliosarcoma), and be candidates for surgical resection
 with Gliadel wafer placement. Patients have to be within 6 weeks of the last major
 surgical procedure.

 -  Age ≥ 18 years

 -  Candidates for Gliadel

 -  If a prior procedure was done, an interval of at least 2 weeks and not > 8 weeks
 between prior major surgical procedure and study enrollment

 -  No prior radiotherapy or chemotherapy for a brain tumor

 -  Karnofsky > 60%

 -  Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/microliters, platelets ≥ 125,000
 cells/microliters

 -  Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of
 normal.

 -  Signed informed consent approved by the Institutional Review Board

 -  If sexually active, patients must agree to use appropriate contraceptive measures for
 the duration of the study and for 6 months afterwards as stated in the informed
 consent.

 Exclusion Criteria:

 -  Pregnancy or breast feeding.

 -  Co-medication that may interfere with study results; e.g. immuno-suppressive agents
 other than corticosteroids.

 -  Active infection requiring IV antibiotics.

 -  Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of
 the grade of the tumor.

 -  Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan.

 -  Prior treatment with Avastin for any condition

 -  Prior, unrelated malignancy requiring active treatment with the exception cervical
 carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the
 skin

 Avastin-Specific Exclusion Criteria:

 -  Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
 diastolic blood pressure > 100 mmHg)

 -  Prior history of hypertensive crisis or hypertensive encephalopathy

 -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

 -  History of myocardial infarction or unstable angina within 6 months prior to study
 enrollment

 -  History of stroke or transient ischemic attack within 6 months prior to study
 enrollment

 -  Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
 recent peripheral arterial thrombosis) within 6 months prior to study enrollment

 -  History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month
 prior to study enrollment

 -  Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic
 anticoagulation)

 -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
 prior to the first Avastin infusion or anticipation of need for major surgical
 procedure during the course of the study

 -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
 access device, within 7 days prior to study enrollment

 -  History of abdominal fistula, gastrointestinal perforation within 6 months prior to
 study enrollment

 -  Serious, non-healing wound, active ulcer, or untreated bone fracture

 -  Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+
 (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should
 undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to
 be eligible).

 -  Known hypersensitivity to any component of Avastin

 -  Pregnant (positive pregnancy test) or lactation. Use of effective means of
 contraception (men and women) in subjects of child-bearing potential