VNP40101M in Treating Young Patients With Recurrent, Progressive, or Refractory Primary Brain Tumors

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.

Eligibility Criteria:
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