Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma
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.
Brain and Central Nervous System Tumors
Drug: polifeprosan 20 with carmustine implant
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas|
- Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma [ Designated as safety issue: Yes ]
- Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants. [ Designated as safety issue: Yes ]
- Tumor response [ Designated as safety issue: No ]
|Study Start Date:||March 2003|
|Study Completion Date:||July 2004|
|Primary Completion Date:||July 2004 (Final data collection date for primary outcome measure)|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00045721
|United States, California|
|UCSF Comprehensive Cancer Center|
|San Francisco, California, United States, 94143-0372|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104-4318|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105-2794|
|United States, Texas|
|Texas Children's Cancer Center|
|Houston, Texas, United States, 77030-2399|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Study Chair:||Ian F. Pollack, MD||Children's Hospital of Pittsburgh|