The current standard of care for patients with GBM, regardless of MGMT methylation, is temozolomide and concurrent radiation. PPX is a powerful radiation enhancer. GBM without MGMT methylation represents the ideal disease site to evaluate a new radiation sensitizer. This subset of patients have inferior survival as compared to patients with MGMT methylation and this variable is being used as a stratification variable and/or eligibility criteria in the phase iii RToG and eMD Serono trials, respectively. Since temozolomide does not statistically improve outcome in patients without MGMT methylation, it does not need to be administered in the investigational PPX arm so there will be no concern about drug interaction. However, temozolomide will be used in both arms following initial chemoradiation.
This will be a randomized phase ii study. Patients with GBM without MGMT methylation undergo 2:1 randomization to the investigational arm, PPX/RT, versus the standard arm temozolomide/RT, respectively. The primary endpoint point of the randomized phase ii study will be PFS. The information from this study will be utilized to plan a phase iii trial.
1. Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV) without MGMT methylation.
2. 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
3. Must be able to tolerate brain MRIs.
4. MGMT methylation will be determined by a central laboratory
5. A diagnostic contrast-enhanced MRI must be performed postoperatively within 42 days prior to study registration.
6. No prior chemotherapy or radiation for brain tumors.
7. Patients with a prior history of low-grade glioma, who did not receive prior radiation of chemotherapy for low grade glioma, but develop a transformation to grade IV brain tumor are eligible.
8. Absolute neutrophil count >= 1,500/uL, and platelet >= 100,000/uL.
Total bilirubin <= 1.5 x upper institutional limit of normal (ULN), and
AST or ALT <= 3x ULN;
9. Peripheral neuropathy must be <= Grade 1
10. Creatinine < 2 x ULN
11. KPS > 60
12. Minimum life expectancy of 12 weeks.
13. Age >18 years.
14. Voluntary, signed informed consent.
15. If the patient is a female of childbearing potential (not surgically sterile or 1 year postmenopausal): must use a medically accepted method of contraception (including abstinence) and must agree to continue use of this method for the duration of the study and for 3 months after participation in the study.
16. If the patient is a male: if sexually active, is currently using an effective barrier method of contraception, and agrees to continue use of this method for the duration of the study and for 3 months after the last administration of study drug.