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

Johns Hopkins Medicine

Status and phase

Completed

Phase 1

Conditions

Brain and Central Nervous System Tumors

Treatments

Drug: arsenic trioxide

Radiation: radiation therapy

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00095771

CDR0000393829

P30CA006973 (U.S. NIH Grant/Contract)

JHOC-J0423

JHOC-04041906

Details and patient eligibility

About

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.

Full 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.

Enrollment

36 estimated patients

Sex

All

Ages

3 to 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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