Acetylcysteine, Mannitol, Combination Chemotherapy, and Sodium Thiosulfate in Treating Children With Malignant Brain Tumors

Summary

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, etoposide phosphate, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Mannitol may help chemotherapy work better by making it easier for these drugs to get to the tumor. Chemoprotective drugs, such as acetylcysteine and sodium thiosulfate, may protect normal cells from the side effects of chemotherapy. Giving acetylcysteine together with mannitol, combination chemotherapy, and sodium thiosulfate may be an effective treatment for malignant brain tumors.

PURPOSE: This phase I trial is studying the side effects and best dose of acetylcysteine when given together with mannitol, combination chemotherapy, and sodium thiosulfate in treating children with malignant brain tumors.

Conditions

• Bone Marrow Suppression
• Brain and Central Nervous System Tumors
• Drug/Agent Toxicity by Tissue/Organ
• Long-term Effects Secondary to Cancer Therapy in Children

Interventions

BIOLOGICAL

filgrastim

DRUG

acetylcysteine

administered i.v. over 30 to 60 minutes

DRUG

carboplatin

(200 mg/m2/day; total dose 400 mg/m2) will be infused i.a. over 10 minutes, in 50-180 cc of normal saline.

DRUG

cyclophosphamide

(330 mg/m2/day; total dose 660 mg/m2) will be infused i.v. in 25-50 cc of normal saline, over approximately 10 minutes.

DRUG

etoposide phosphate

(200 mg/m2/day; total dose 400 mg/m2) will be infused i.v. in 25-100 cc of normal saline, over approximately 10 minutes, immediately following the cyclophosphamide.

DRUG

mannitol

(25%) delivered i.a. at a pre-determined flow rate over 30 seconds. The flow rate will be determined by iodinated contrast injection and fluoroscopy as the lowest infusion rate in which there is retrograde flow from the arterial catheter. The rate and volume of mannitol infused will be approximately 4-12 cc/sec x 30 seconds.

DRUG

sodium thiosulfate

STS is available as a 25% (250 mg/ml) solution. The dose of STS administered 4 hours after carboplatin is 16 gm/m2. The dose of STS administered 8 hours after carboplatin is 16 gm/m2. Actual dose to be administered will be determined and mixed with an equivalent amount of sterile water (1 ml:1 ml) for infusion.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• OHSU Knight Cancer Institute

  lead OTHER

Principal Investigators

• Edward A. Neuwelt, MD · OHSU Knight Cancer Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Year

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2004-12-31

Primary Completion

2006-02-17

Completion

2006-02-17

Countries

• United States

Study Locations