Clinical Trial Finder

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)

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.

Arms

Experimental: radiation plus PPX(CT2103

Radiation therapy, Monday through Friday, for 6 weeks for a total of 30 treatments - intravenous PPX every week x 6 weeks for a total of 6 treatments

Active Comparator: radiation + Temozolomide

Radiation therapy, Monday through Friday, for 6 weeks for a total of 30 treatments - Daily oral temozolomide(TMZ) (7 days) x 6 wks for a total of 42 days

Interventions

Drug: - PPX (CT2103)

XRT: 60 Gy at 2 Gy/fraction x 30 fractions PPX: 50 mg/m2/week x 6 weeks during radiation Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum.

Drug: - Temozolomide

XRT: 60 Gy at 2 Gy/fraction x 30 fractions Temozolomide, 75 mg/m2/day, 7 days per week, from the first to the last day of radiotherapy Temozolomide maintenance: Beginning 4 weeks after completion of chemoradiation, temozolomide d1-5 of 28 day cycle for 12 cycle maximum