A Phase I Trial of Arsenic Trioxide in the Treatment of Infiltrating Gliomas of Childhood
3 Years
21 Years
Both
Brain and Central Nervous System Tumors
Trial Information
A Phase I Trial of Arsenic Trioxide in the Treatment of Infiltrating Gliomas of Childhood
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.
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose as assessed by NCI CTCAE v. 3.0 following study completion
Safety Issue:
Yes
Principal Investigator
Kenneth J. Cohen, MD, MBA
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
CDR0000393829
NCT ID:
NCT00095771
Start Date:
November 2004
Completion Date:
January 2011
Related Keywords:
- Brain and Central Nervous System Tumors
- untreated childhood brain stem glioma
- childhood high-grade cerebral astrocytoma
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
