RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving arsenic trioxide and temozolomide together with radiation therapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of arsenic trioxide and temozolomide when given together with radiation therapy and to see how well they work in treating patients with malignant glioma that has been removed by surgery.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of arsenic trioxide and temozolomide when combined with radiotherapy in patients with resected supratentorial malignant glioma. (Phase I)
• Determine the toxicity of this regimen in these patients. (Phase I)

Secondary

• Determine the 6- and 12-month progression-free survival of patients treated with this regimen once an MTD is reached. (Phase II)
• Determine the radiographic response for patients treated with the above regimen. (Phase II)
• Determine the safety of this regimen in these patients. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of arsenic trioxide and temozolomide followed by a phase II study.

• Phase I: Patients undergo radiotherapy once daily 5 days a week and receive oral temozolomide once daily for approximately 6½ weeks. Patients also receive arsenic trioxide IV over 1-4 hours once daily, 5 days a week in week 1 and then twice a week in weeks 2-7. Beginning within 3-5 weeks after completion of radiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 1 year in the absence of disease progression and unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of arsenic trioxide and temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients undergo radiotherapy and receive arsenic trioxide and temozolomide as in phase I at the MTD. Patients then receive temozolomide as in phase I for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for the phase I portion of this study. A total of 25 patients will be accrued for the phase II portion of this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial malignant glioma of 1 of the following types:

  • Glioblastoma multiforme
  • Gliosarcoma
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed gliomas
  • Anaplastic gliomas not otherwise specified

• Has undergone surgical resection of tumor

  • Patients with biopsy only are eligible
  • Evaluable or measurable disease following resection of recurrent tumor is not mandated for entry into the study

• No brain metastases

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy > 3 months
• WBC > 3,000/mm^3
• Absolute neutrophil count > 2,000/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 10 g/dL (eligibility level for hemoglobin may be reached by transfusion)
• Creatinine ≤ 1.5 mg/dL
• Bilirubin ≤ 2 mg/dL
• Transaminases ≤ 2 times the upper limit of normal
• Serum potassium* > 4.0 mEq/dL
• Serum magnesium* > 1.8 mg/dL NOTE: *If these serum electrolytes are below the specified limits on the baseline laboratory tests, supplemental electrolytes should be administered to bring the serum concentrations to these levels before administering arsenic trioxide
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No second-degree heart block
• QT interval ≤ 460 msec
• No other malignancy within the past 3 years except curatively treated carcinoma in situ or basal cell carcinoma of the skin
• Patients who cannot undergo MRI are not eligible for this study
• No other serious concurrent infection or other medical illness that would jeopardize the ability of the patient to receive the therapy in this protocol with reasonable safety

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Patients must have recovered from the effects of surgery prior to the start of treatment (10-14 days minimum) and be maintained on a stable corticosteroid regimen for 5 days
• Concurrent glucocorticoid therapy allowed at the smallest effective dose
• Patients must be on non-enzyme-inducing anti-convulsants to minimize any drug reaction
• No prior radiation therapy, chemotherapy, immunotherapy, therapy with biologic agents (including immunotoxins, immunoconjugates, antisense agents, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their brain tumor