RATIONALE: Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, and etoposide phosphate, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways may kill more tumor cells. Chemoprotective drugs, such as sodium thiosulfate, may protect blood platelets from the side effects of chemotherapy.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining carboplatin, cyclophosphamide, and etoposide or etoposide phosphate with or without sodium thiosulfate in treating patients who have high-grade glioma.

Condition	Treatment or Intervention	Phase
adult anaplastic astrocytoma adult anaplastic ependymoma adult anaplastic oligodendroglioma adult brain tumor adult glioblastoma Thrombocytopenia	Drug: carboplatin  Drug: cyclophosphamide  Drug: etoposide  Drug: etoposide phosphate  Drug: filgrastim  Drug: sodium thiosulfate  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: hematologic toxicity attenuation  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the effect of delayed administration of high-dose sodium thiosulfate on platelet counts in patients with high-grade glioma undergoing treatment with intra-arterial carboplatin, cyclophosphamide, and etoposide or etoposide phosphate.

Secondary

• Determine the effect of delayed administration of high-dose sodium thiosulfate on granulocyte and erythrocyte counts in patients treated with this chemotherapy regimen.
• Determine the tumor response in patients treated with this chemotherapy regimen with or without delayed high-dose sodium thiosulfate.
• Determine hearing changes at higher frequencies in the standard testing range (i.e., 4,000 and 8,000 Hz) and at higher frequencies above standard testing range (i.e., 9,000 and 16,000 Hz) in patients treated with these regimens.
• Determine the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology type (glioblastoma multiforme vs anaplastic astrocytoma). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cyclophosphamide IV over 10 minutes, etoposide phosphate IV over 10 minutes (or etoposide IV), and carboplatin intra-arterially over 10 minutes on day 1. Beginning on day 3, patients receive filgrastim (G-CSF) subcutaneously once daily for 7-10 days until blood counts recover.
• Arm II: Patients receive cyclophosphamide, etoposide phosphate or etoposide, carboplatin, and G-CSF as in arm I. At 4 and 8 hours after carboplatin administration, patients receive high-dose sodium thiosulfate IV over 15 minutes. In both arms, treatment repeats every 4 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 6 months during study treatment, and then within 30 days after the final study treatment.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed high-grade glioma by needle biopsy, open biopsy, or surgical resection
• No rapidly progressing CNS disease with associated neurological deterioration

PATIENT CHARACTERISTICS: Age

• 18 to 75

Performance status

• ECOG 0-2 OR
• Karnofsky 50-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,500/mm^3
• Absolute granulocyte count at least 1,200/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin less than 2.0 mg/dL
• SGOT/SGPT less than 2.5 times upper limit of normal

Renal

• Creatinine less than 1.8 mg/dL

Cardiovascular

• Adequate cardiovascular function to tolerate monitored anesthesia

Pulmonay

• Adequate pulmonary function to tolerate monitored anesthesia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for at least 2 months before and during study participation
• No uncontrolled clinically significant confounding medical condition within the past 30 days
• No contraindication to the study medications

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 2 weeks since prior focal or systemic radiotherapy

Surgery

• Prior surgery or biopsy allowed

Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting

Study chairs or principal investigators

Edward A. Neuwelt, MD,  Principal Investigator,  Oregon Health and Science University   

Study ID Numbers:  CDR0000346101; OHSU-7328; OHSU-ONC-02059-L; NCT00075387
Record last reviewed:  January 2004
Last Updated:  March 3, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075387
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08