RATIONALE: Drugs such as arsenic trioxide may stop the growth of malignant glioma by stopping blood flow to the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining arsenic trioxide with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide and radiation therapy in treating patients with newly diagnosed malignant glioma.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of 2 different dosing schedules of arsenic trioxide in combination with radiotherapy in patients with newly diagnosed malignant glioma.
• Determine the toxicity of these regimens in these patients.

Secondary

• Determine the survival of patients treated with these regimens.
• Evaluate the effect of arsenic trioxide on tumor vasculature in these patients.
• Determine the pharmacokinetics of arsenic trioxide in these patients.

OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of arsenic trioxide. Patients are assigned to 1 of 2 treatment groups.

• Group A: Patients receive arsenic trioxide IV over 2 hours once weekly for 6 weeks.
• Group B: Patients receive arsenic trioxide at a lower dose IV over 2 hours twice weekly for 6 weeks.

Patients in both groups also undergo radiotherapy once daily 5 days a week for 6 weeks.

In both groups, cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly for 4 weeks and then every 2 months thereafter.

PROJECTED ACCRUAL: Approximately 18-30 patients will be accrued for this study within 6-15 months.

• Drug: arsenic trioxide
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin less than 2 mg/dL
• AST/ALT less than 4 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No second-degree heart block

Other

• Potassium greater than 3.0 mEq/L and less than 5.5 mEq/L
• Magnesium greater than 1.2 mEq/L and less than 2.5 mEq/L
• Mini mental score at least 15
• Able to undergo MRI
• No concurrent serious infection
• No other medical illness that would preclude study participation
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy or biologic therapy for this disease (e.g., immunotoxins, immunoconjugates, antisense therapy, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cell therapy, or gene therapy)

Chemotherapy

• No prior chemotherapy for this disease

Endocrine therapy

• No prior hormonal therapy for this disease
• Prior glucocorticoid therapy allowed
• Must be on a stable corticosteroid regimen (i.e., no increase for 5 days)

Radiotherapy

• No prior radiotherapy for this disease

Surgery

• Recovered from prior surgery
• Prior surgery allowed

Other

• At least 5 days since prior drugs that are known to prolong QT interval

  • Patients who continue to experience QT prolongation 5 days after discontinuation of the drug are not eligible
• No other prior therapy for this disease
• No concurrent amphotericin B
• No drugs that are known to prolong QT interval during or for 2 weeks after study participation