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

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells and may be an effective treatment for patients with glioma. Drugs such as arsenic trioxide may also make the tumor cells more sensitive to radiation therapy. Combining arsenic trioxide with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining arsenic trioxide with radiation therapy in treating patients who have 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.

Eligibility Criteria:
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