Temozolomide and O6-benzylguanine in Treating Patients With Newly Diagnosed, Recurrent, or Progressive Anaplastic Glioma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and O6-benzylguanine in treating patients who have newly diagnosed, recurrent, or progressive anaplastic glioma.
|Brain and Central Nervous System Tumors||Drug: O6-benzylguanine Drug: temozolomide Procedure: conventional surgery||Phase 1|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Phase I Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Newly Diagnosed (Part 1) or Recurrent/Progressive (Parts 1 and 2) Cerebral Anaplastic Gliomas|
|Study Start Date:||March 2001|
|Study Completion Date:||August 2004|
|Primary Completion Date:||August 2004 (Final data collection date for primary outcome measure)|
- Determine the dose of O6-benzylguanine (O6-BG) effective in producing complete suppression of tumor O6-alkylguanine-DNA alkyltransferase activity in patients with newly diagnosed (closed to accrual 12/19/2000) or recurrent or progressive cerebral anaplastic glioma.
- Determine the maximum tolerated dose of temozolomide administered after O6-BG in these patients.
- Determine the toxicity of this regimen in these patients.
- Determine the anti-tumor response in patients treated with this regimen.
OUTLINE: This is a dose-escalation, multicenter study.
- Part I: Patients receive escalating doses of O6-benzylguanine (O6-BG) IV continuously for 49 hours until the dose that produces the target depletion of tumor O6-alkylguanine-DNA alkyltransferase (AGT) is determined. Patients undergo a craniotomy after completion of the O6-BG infusion. (closed to accrual 12/19/2000)
- Part II: After determination of the O6-BG dose in Part I, patients with recurrent malignant gliomas receive O6-BG IV continuously for 49 hours beginning on day 1. Patients also receive oral temozolomide on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.
PROJECTED ACCRUAL: Approximately 20-30 patients (with 14 patients participating in Part II) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006474
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|Study Chair:||Henry S. Friedman, MD||Duke Cancer Institute|