ABT-888, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme)

  • Newly diagnosed disease

• Patients enrolled in the phase I initial safety portion of the study must meet the following additional criteria:

  • Received 90% of planned radiotherapy and ≥ 80% of planned concurrent temozolomide within the past 28-49 days

    • No grade 3-4 toxicity attributed to temozolomide
  • Has undergone gadolinium MRI or contrast CT scan within the past 28 days

• Patients enrolled in the phase I dose-escalation/phase II portion of the study must meet the following additional criteria:

  • Recovered from immediate post-operative period and maintained on a stable corticosteroid regimen (no increase in 5 days) prior to starting study treatment
  • Has undergone gadolinium MRI or contrast CT scan within the past 14 days

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy ≥ 3 months
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min
• Total bilirubin ≤ 1.5 mg/dL
• Transaminases ≤ 2.5 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for 3 months after completion of study therapy
• Mini Mental State Exam score ≥ 15
• Able to swallow and retain oral medications
• No concurrent serious infection or medical illness that would jeopardize the ability of the patient to receive study treatment with reasonable safety
• No other malignancy within the past 5 years except for curatively treated carcinoma in situ or basal cell carcinoma of the skin
• No known uncontrolled seizure disorder (i.e., status epilepticus) or seizures occurring ≥ 3 times per week over the past month

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 10 days since prior cytochrome P450-inducing anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, primidone, or oxcarbazepine)
• At least 1 week since prior biopsy or resection of tumor (for patients enrolled in the phase I dose-escalation/phase II portion of the study)

• No prior radiotherapy, chemotherapy, immunotherapy, hormonal therapy, or biological therapy (including immunotoxins, immunoconjugates, antisense therapy, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy) for treatment of brain tumor (for patients enrolled in the phase I dose-escalation/phase II portion of the study)

  • Prior glucocorticoid therapy allowed
• No other prior chemotherapy or investigational agents (for patients enrolled in the phase I initial safety portion of the study)
• Prior Gliadel wafers allowed (for patients enrolled in the phase I portion of the study)
• No prior Gliadel wafers (for patients enrolled in the phase II portion of the study)