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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I Trial of Arsenic Trioxide in the Treatment of Infiltrating Gliomas of Childhood

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: arsenic trioxide
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: arsenic trioxide|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose as assessed by NCI CTCAE v. 3.0 following study completion |  |  | 
| Safety as assessed by NCI CTCAE v. 3.0 following study completion |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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untreated childhood brain stem glioma, childhood high-grade cerebral astrocytoma