Phase I Study Of Cloretazine (VNP40101M) In Children With Recurrent, Progressive Or Refractory Primary Brain Tumors

Inclusion 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