O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors

Phase 2

Completed

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
O6-BG and TMZ	temozolomide	O6-benzylguanine (O6-BG) and temozolomide (TMZ)
O6-BG and TMZ	O6-benzylguanine	O6-benzylguanine (O6-BG) and temozolomide (TMZ)

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With an Objective Response (Complete Response or Partial Response)	Week 8, 16, 24, 32, and 40 after starting therapy	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.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Grade 3 or 4 Adverse Events at Least Possibly Related to the Combination of O6-benzylguanine and Temozolomide	From day 1 of therapy up to 49 months	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.

Locations (11): UCSF Helen Diller Family Comprehensive Cancer Center
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San Francisco, California, United States
Children's National Medical Center
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Washington, District of Columbia, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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Boston, Massachusetts, United States
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
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Houston, Texas, United States
Children's Memorial Hospital - Chicago
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Chicago, Illinois, United States
Duke Comprehensive Cancer Center
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Durham, North Carolina, United States
Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
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Pittsburgh, Pennsylvania, United States
Dan L. Duncan Cancer Center at Baylor College of Medicine
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Houston, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
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Seattle, Washington, United States
St. Jude Children's Research Hospital
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Memphis, Tennessee, United States