• Maximum tolerated dose of arsenic trioxide and temozolomide in combination with radiotherapy [ Designated as safety issue: Yes ]
  
• Toxicity [ Designated as safety issue: Yes ]
  

• Progression free and overall survival at 6 and 12 months [ Designated as safety issue: No ]
  
• Radiographic response at 6 and 12 months [ Designated as safety issue: No ]
  

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