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
- 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
- Determine the maximum tolerated dose of temozolomide administered after O6-BG in these
- 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.
Primary Purpose: Treatment
Henry S. Friedman, MD
Duke Cancer Institute
United States: Federal Government
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|