NCT00045721

Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma

Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Pediatric Brain Tumor Consortium · Network
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemotherapy placed into the surrounding tissue after surgery to remove the tumor may kill any remaining tumor cells. O(6)-benzylguanine may increase the effectiveness of carmustine by making tumor cells more sensitive to the drug. PURPOSE: Phase I trial to study the safety of combining O(6)-benzylguanine with carmustine implants in treating children who have recurrent malignant glioma.

Detailed description

OBJECTIVES: * Determine the dose of O(6)-benzylguanine that reliably inhibits alkylguanine-DNA alkyltransferase activity in pediatric patients with recurrent malignant glioma. * Describe the toxic effects of O(6)-benzylguanine with carmustine implant (Gliadel) in these patients. * Investigate antitumor response in patients treated with this regimen. * Characterize the pharmacokinetics of O(6)-benzylguanine when administered continuously over a 9-day period. OUTLINE: This is a multicenter, dose-escalation study of O(6)-benzylguanine. Patients receive O(6)-benzylguanine (O6-BG) IV over 1 hour immediately followed by O6-BG IV continuously for 9 days. Two days after initiation of continuous infusion of O6-BG, patients undergo maximal tumor debulking. At the time of surgery, patients receive up to 8 polifeprosan 20 wafers with carmustine (Gliadel) implanted into the resection cavity. Cohorts of up to 14 patients receive escalating doses of continuous infusion O6-BG until the optimally biologically effective dose (BED) is determined. The BED is defined as the dose at which at least 11 of 14 patients meet the target of complete suppression of alkylguanine-DNA alkyltransferase levels. Patients are followed at day 11, at weeks 2, 4, 6, 8, and 12, at months 6, 9, and 12, every 6 months for 4 years, and then annually for 5 years. PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 2 years.

Conditions

• Brain and Central Nervous System Tumors

Interventions

Type	Name	Description
DRUG	O6-benzylguanine
DRUG	polifeprosan 20 with carmustine implant
PROCEDURE	adjuvant therapy
PROCEDURE	conventional surgery
PROCEDURE	neoadjuvant therapy

Timeline

• Start date: 2003-03-01
• Primary completion: 2004-07-01
• Completion: 2004-07-01
• First posted: 2003-01-27
• Last updated: 2009-10-16

Locations

9 sites across 1 country: United States