A Phase II Trial of O6-Benzylguanine and Temozolomide in Pediatric Patients With Recurrent or Progressive High-Grade Gliomas and Recurrent or Progressive Brainstem Tumors
I. Determine the sustained objective response rate to the combination of O6-benzylguanine
and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and
brain stem tumors.
I. Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to tumor type
(high-grade gliomas vs brain stem tumors).
Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide on days 1-5.
Treatment repeats every 28 days for up to 12 courses in the absence of disease progression
or unacceptable toxicity.
After completion of study treatment, patients are followed to the earliest of 30 days
following discontinuation of therapy or the initiation of additional anti-cancer therapy or
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Percentage of Participants With an Objective Response (Complete Response or Partial Response)
The primary endpoint is to assess the percentage of participants with a sustained objective response (complete response (CR) or partial response (PR)). Response is assessed by magnetic resonance imaging (MRI) per the following criteria: CR - disappearance of tumor and PR - ≥50% reduction in tumor based on the maximal cross-sectional measurements. The response must be sustained for at least 8 weeks, and the date of the confirmed sustained response is the date at which the response was first noted by MRI.
Week 8, 16, 24, 32, and 40 after starting therapy
Katherine Warren, MD
National Cancer Institute (NCI)
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|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital||Houston, Texas 77030-2399|
|Dan L. Duncan Cancer Center at Baylor College of Medicine||Houston, Texas 77030|