This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors. Drugs used in chemotherapy, such as O6-benzylguanine and temozolomide , work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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 death. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. O6-Benzylguanine, 120 mg/m\^2, will be administered as a one-hour intravenous (IV) infusion, daily for 5 days. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses of therapy.
Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Temozolomide, 75 mg/m\^2 (rounded to the nearest 5 mg, the size of the smallest capsule) will be given orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses.
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
Duke Comprehensive Cancer Center
Durham, North Carolina, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States
...and 1 more locations
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.
Time frame: Week 8, 16, 24, 32, and 40 after starting therapy
Number of Patients With Grade 3 or 4 Adverse Events at Least Possibly Related to the Combination of O6-benzylguanine and Temozolomide
Clinical and laboratory studies to assess adverse events are obtained at least every four weeks (prior to each course) with some laboratory studies obtained every 2 weeks. Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). Attribution of each adverse event to the treatment regimen is determined by the participant's attending physician at the enrolling institution and verified by the study chair.
Time frame: From day 1 of therapy up to 49 months
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