Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
- 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
- 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
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.
Endpoint Classification: Safety Study, Primary Purpose: Treatment
Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma
Ian F. Pollack, MD
Children's Hospital of Pittsburgh
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Texas Children's Cancer Center||Houston, Texas 77030-2399|
|UCSF Comprehensive Cancer Center||San Francisco, California 94115|