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)