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

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult glioblastoma, adult gliosarcoma, adult giant cell glioblastoma Read More

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)