A Dose Per Fraction Escalation Trial of Hypofractionated IMRT With Temozolomide for Newly Diagnosed Glioblastoma

Inclusion Criteria:

* Histopathologically confirmed WHO grade IV astrocytoma (GBM), tumor can be supra- or infra-tentorial in location but not located in the brain stem.
* Solitary or multifocal tumor.
* Tumor can be biopsied or resected, either totally or sub-totally.
* A pre-radiation therapy brain MRI is mandatory.
* Surgical cavity or surgical cavity + T1 enhancing residual tumor ≤ 6 cm in the largest diameter on the pre-radiation therapy MRI. In the case of multifocal tumor, the combined largest diameter of T1 enhancing tumor + surgical cavity ≤ 6 cm.
* Placement of bis-chloronitrosourea (BCNU) wafers at the time of surgery is allowed.
* Age \> 18 years at time of registration.
* Estimated survival of at least 3 months.
* Zubrod Performance Scale of 0-2 (Karnofsky performance scale ≥ 60).
* Hgb \> 9 gm; absolute neutrophil count (ANC) \> 1500/ul; platelets \> 100,000; Creatinine \< 1.5 times the upper limit of laboratory normal value; Bilirubin \< 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) \< 3 times the upper limit of laboratory normal value.
* Patients must sign study-specific informed consent form prior to registration.
* Men and women and members of all ethnic groups are eligible for this trial.
* Radiation therapy and chemotherapy must start within 8 weeks of tumor resection or biopsy

Exclusion Criteria:

* Patients with contraindications for MRI scanning.
* Prior temozolomide chemotherapy.
* Prior brain irradiation.
* Evidence of severe or uncontrolled psychiatric or systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) that would interfere with study protocol as judged by the investigator.
* Acquired Immune Deficiency (HIV (+)/AIDS)
* Patients being treated on any other clinical protocols within 30 days prior to study entry or during participation in the study.
* Pregnant women or breast feeding women. Women of childbearing potential must practice medically approved contraceptive precautions. Men should be counseled and agreeable to follow acceptable birth control methods.
* Active connective tissue disorders, such as active lupus or scleroderma.
* Concurrent active malignancy at other sites.
* Frequent vomiting of medical condition which could interfere with oral medication intake (e.g. partial bowel obstruction).