Arsenic Trioxide and Radiation Therapy in Treating Young Patients With Newly Diagnosed Gliomas

OBJECTIVES:

• Determine the maximum tolerated dose of arsenic trioxide when administered with radiotherapy in pediatric patients with newly diagnosed anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or intrinsic pontine glioma.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of arsenic trioxide (ATO).

Patients undergo radiotherapy once daily, 5 days a week, for approximately 6 weeks. Patients concurrently receive ATO IV over 1 hour, 1-5 times weekly, for approximately 6 weeks in the absence of disease progression or unacceptable toxicity.

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

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 3-36 months.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Clinical and neuroradiographic findings consistent with intrinsic pontine glioma
• Histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, or gliosarcoma

• Multifocal high-grade gliomas allowed
• No exophytic tumors
• No focal lesions
• No underlying diagnosis of neurofibromatosis
• No tumors originating in anatomic structures adjacent to the cerebellar peduncle or cervical medullary junction

PATIENT CHARACTERISTICS:

Age

• 3 to 21

Performance status

• Karnofsky 60-100% OR
• Lansky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Hemoglobin > 10 g/dL
• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin < 2.0 mg/dL
• Alkaline phosphatase < 2.5 times upper limit of normal (ULN)
• Transaminases < 2.5 times ULN

Renal

• Creatinine < 2.0 times ULN

Cardiovascular

• No second-degree heart block
• No absolute QTc interval > 500 msec with normal potassium and magnesium levels

Other

• Not pregnant or nursing
• Negative pregnancy test
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ
• No other serious medical illness
• Able to undergo MRI

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 28 days since prior biologic therapy
• No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy

• No prior arsenic trioxide

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Prior surgery for the brain tumor allowed

Other

• No other prior therapy for the brain tumor
• More than 28 days since prior investigational drugs or devices
• No concurrent amphotericin B