Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed brain tumors, including any of the following: - Brain stem glioma.

• - Primitive neuroectodermal tumor.

• - CNS germ cell tumor.

• - Malignant glioma.

• - Diagnosis based on any of the following: - CT-assisted or stereotactic biopsy.

• - Open biopsy.

• - Surgical resection.

• - Cerebrospinal fluid cytology.

• - Elevated tumor markers.

• - Unequivocal radiographic changes (for patients with brain stem glioma or optic glioma) - All tumor types, except brain stem glioma, must be recurrent.

• - No radiographic signs of intracranial herniation and/or spinal cord block.

PATIENT CHARACTERISTICS: Performance status.

• - ECOG 0-2.

Life expectancy.

• - At least 90 days.

Hematopoietic.

• - WBC ≥ 2,500/mm^3.

• - Absolute granulocyte count ≥ 1,200/mm^3.

• - Platelet count ≥ 100,000/mm^3.

Hepatic.

• - SGOT and SGPT < 2.5 times upper limit of normal.

• - Bilirubin < 2.0 mg/dL.

Renal.

• - Creatinine < 1.8 mg/dL.

Pulmonary.

• - No history of clinically significant reactive airway disease.

Other.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - No significant risk for general anesthesia.

• - No uncontrolled, clinically significant, confounding medical condition within the past 30 days.

• - No contraindication to study drugs.

PRIOR CONCURRENT THERAPY: Chemotherapy.

• - At least 28 days since prior systemic chemotherapy.

Radiotherapy.

• - At least 3 months since prior total spine radiotherapy.

• - At least 14 days since prior cranial radiotherapy.

• - Prior systemic radiotherapy allowed.

Surgery. - See Disease Characteristics

OBJECTIVES: Primary.

• - Determine the toxicity and maximum tolerated dose of acetylcysteine when given in combination with blood-brain barrier disruption treatment with mannitol, combination chemotherapy comprising cyclophosphamide, etoposide phosphate, and carboplatin, and delayed high-dose sodium thiosulfate in pediatric patients with malignant brain tumors.

Secondary.

• - Determine the blood/bone marrow toxicity of this regimen in these patients.

• - Determine tumor response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of acetylcysteine. Patients receive acetylcysteine IV over 30-60 minutes followed, at least 15 minutes later, by x-ray-guided femoral artery catheterization under general anesthesia on days 1 and 2. After placement of the catheter, patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes, mannitol intra-arterially (IA) over 30 seconds, and carboplatin IA over 10 minutes also on days 1 and 2. Patients then receive high-dose sodium thiosulfate IV over 15 minutes 4 hours after completion of carboplatin. Some patients may receive a second dose of sodium thiosulfate 8 hours after completion of carboplatin. Beginning 48 hours after the last dose of chemotherapy on day 2, patients receive filgrastim (G-CSF) subcutaneously once daily for 7-10 days or until blood counts recover. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of acetylcysteine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 3 patients are treated at the MTD. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.