Clinical Trial Finder

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

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.#46;no), autologous bone marrow transplant (yes vs.#46;no), and > 2 myelosuppressive chemotherapy or myelosuppressive biologic therapy regimens (yes vs.#46;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.