RATIONALE: Drugs used in chemotherapy, such as VNP40101M, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of VNP40101M in treating young patients with recurrent, progressive, or refractory primary brain tumors.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of VNP40101M in pediatric patients with recurrent, progressive, or refractory primary brain tumors.

Secondary

• Determine the pharmacokinetics of this drug and its active metabolite VNP4090CE in these patients.
• Determine the efficacy of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to receiving ≥ 1 of the following prior therapies: craniospinal irradiation (yes vs no), autologous bone marrow transplant (yes vs no), and > 2 myelosuppressive chemotherapy or myelosuppressive biologic therapy regimens (yes vs no).

Patients receive VNP40101M IV over 30 minutes on days 1-5. Treatment repeats every 42 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 2-6 patients per stratum receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.

Patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 4-60 patients (2-30 per stratum) will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed* primary brain tumor, including benign brain tumors (e.g., low-grade glioma)

  • Recurrent or progressive disease OR refractory to standard therapy NOTE: *Patients with intrinsic brain stem or diffuse optic pathway tumors do not require histological confirmation, but must have clinical and/or radiographic evidence of disease progression

• No bone marrow disease

PATIENT CHARACTERISTICS:

Age

• 21 and under

Performance status

• Karnofsky 50-100% (for patients > 16 years of age) OR
• Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3*
• Platelet count ≥ 100,000/mm^3*
• Hemoglobin ≥ 8 g/dL* NOTE: *Unsupported

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN
• No overt hepatic disease

Renal

• BUN < 25 mg/dL
• Creatinine ≤ 1.5 times ULN for age OR
• Glomerular filtration rate > 70 mL/min
• No overt renal disease

Cardiovascular

• Shortening fraction ≥ 30% by echocardiogram OR
• Ejection fraction ≥ 50% by gated radionucleotide study
• No clinically significant cardiac arrhythmia by EKG
• No overt cardiac disease

Pulmonary

• DLCO ≥ 60% of predicted
• Chest X-ray normal (defined as absence of pulmonary infiltrates, pneumonitis, pleural effusion, pulmonary hemorrhage, or fibrosis) AND a resting pulse oximetry reading of > 94% in room air (for patients who cannot perform the DLCO)
• No overt pulmonary disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Neurologic deficits allowed provided there has been no deficit progression for ≥ 1 week before study entry
• No uncontrolled infection
• No known hypersensitivity to polyethylene glycol

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 6 months since prior allogeneic bone marrow or stem cell transplantation
• At least 3 months since prior autologous bone marrow or stem cell transplantation
• More than 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
• At least 3 weeks since prior myelosuppressive anticancer biologic therapy
• No concurrent routine colony-stimulating factors

Chemotherapy

• At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week before study entry

Radiotherapy

• At least 3 months since prior craniospinal irradiation ≥ 18 Gy
• At least 2 weeks since prior focal irradiation to the primary tumor and/or symptomatic metastatic sites

Surgery

• Not specified

Other

• At least 7 days since prior nonmyelosuppressive anticancer therapy
• At least 7 days since prior investigational agents
• Concurrent enzyme-inducing anticonvulsant drugs allowed
• No other concurrent anticancer or experimental agents or therapies