To obtain preliminary data in a randomized phase II study whether PPX/RT improves progression-free survival as compared to temozolomide/RT for patients with GBM without MGMT methylation.

To evaluate the toxicities of PPX/RT To evaluate neuro-cognitive functional assessments of patients with GBM receiving PPX/RT To obtain preliminary data in a randomized phase II study whether PPX/RT improves overall survival as compared to temozolomide /RT for patients with GBM without MGMT methylation to facilitate planning a phase III study.

Inclusion Criteria:

• Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV)

• GBM must have unmethylated MGMT as determined by central laboratory

• Diagnosis of GBM must be made by biopsy or surgical excision, either partial or complete; as long as there is sufficient tissue to determine MGMT status

• No prior chemotherapy or radiation for brain tumor

• Must be able to tolerate brain MRIs.

  *A diagnostic contrast-enhanced MRI must be performed postoperatively within 42 days prior to study registration.

• KPS >60.

• Age > 18

• Life expectancy of at least 3 months.

• Absolute neutrophil count > 1500/mm3, Platelets > 100,000/mm,

• Creatinine < 2 x ULN

• ALT or AST < 3 x upper limit of normal (ULN) and total bilirubin < 1.5x ULN.

• Patients with a prior history of low grade glioma who did not receive prior radiation or chemotherapy with transformation to grade IV brain tumor are eligible.

• Women must be non-lactating, and surgically sterile, post-menopausal or have a negative serum pregnancy test and agree to use adequate birth control. Males must agree to use adequate birth control.

• Voluntary, signed informed consent.

Exclusion Criteria:

• Acute infection or other medical condition that would impair study treatment
• No other active invasive malignancy unless disease free for at least 3 years.
• Prior temozolomide or PPX.
• Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
• Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
• No diffuse leptomeningeal disease, or gliomatosis cerebri.
• Use of any other experimental chemotherapy drug within the 60 days prior to randomization and during the trial. (Use of a non-chemotherapy investigational agent must be approved by the Brown University Oncology Group)