Brain and Central Nervous System Tumors
Conditions
Keywords
untreated childhood brain stem glioma, childhood high-grade cerebral astrocytoma
Brief summary
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
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.
Interventions
DRUGarsenic trioxide
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | 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 | — |
Countries
United States
Outcome results
None listed