A Phase I/II Trial of Arsenic Trioxide and Temozolomide in Combination With Radiation Therapy for Patients With Malignant Gliomas

Inclusion Criteria

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