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
PURPOSE: Phase I trial to study the effectiveness of combining arsenic trioxide with
radiation therapy in treating patients who have newly diagnosed gliomas.
- 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
- Diagnosis of 1 of the following:
- Clinical and neuroradiographic findings consistent with intrinsic pontine glioma
- Histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, or
- 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
- 3 to 21
- Karnofsky 60-100% OR
- Lansky 60-100%
- Not specified
- Absolute neutrophil count > 1,500/mm^3
- Hemoglobin > 10 g/dL
- Platelet count > 100,000/mm^3
- Bilirubin < 2.0 mg/dL
- Alkaline phosphatase < 2.5 times upper limit of normal (ULN)
- Transaminases < 2.5 times ULN
- Creatinine < 2.0 times ULN
- No second-degree heart block
- No absolute QTc interval > 500 msec with normal potassium and magnesium levels
- 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:
- More than 28 days since prior biologic therapy
- No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim
- No prior arsenic trioxide
- Not specified
- Not specified
- Prior surgery for the brain tumor allowed
- No other prior therapy for the brain tumor
- More than 28 days since prior investigational drugs or devices
- No concurrent amphotericin B