Clinical Trial Finder

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

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.

Arms

Experimental: Radiation + temozolomide and arsenic trioxide

Radiation therapy followed by the combination of temozolomide and arsenic trioxide at the maximum tolerated dose determined in phase 1

Interventions

Drug: - arsenic trioxide

Arsenic trioxide administered intravenously at a dose of 0.20mg/kg Daily x 5 week then twice per week

Drug: - temozolomide

Temozolomide administered orally once per day 1 hour prior to radiation therapy at a dose of 75 mg/m2 x 42 days; at a dose of 200mg/m2 for 5 days every cycle (1 cycle = 28 days) after radiation therapy

Radiation: - radiation therapy

All patients will receive 5940-6120 cGy of radiation therapy as 28-33 treatments/fractions (180-200 cGy/treatment) depending on whether they receive standard 3-D conformal radiation therapy or intensity modulated radiation therapy.