PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation

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)