Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors
- Determine the maximum tolerated dose of temozolomide administered with a biologically
active dose of O6-benzylguanine (O6-BG) in children with refractory solid tumors.
- Determine the dose-limiting toxicity and the toxicity profile of this combination in
- Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in
- Assess the plasma pharmacokinetics of this combination in these patients.
- Correlate levels of alanine-glyoxylate aminotransferase in peripheral blood mononuclear
cells with the degree of hematologic toxicity of this combination in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive O6-benzylguanine (O6-BG) IV over 1 hour followed 30 minutes later by oral
temozolomide daily for 5 days. Treatment continues every 28 days for up to 12 courses in the
absence of unacceptable toxicity or disease progression.
Sequential dose escalation of O6-BG is followed by sequential dose escalation of
temozolomide. Cohorts of 3-6 patients receive escalating doses of O6-BG and temozolomide
until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose
preceding that at which at least 2 of 3 or 6 patients experience dose-limiting toxicity.
Quality of life is assessed at baseline and prior to courses 1, 3, 6, 8, and 12.
PROJECTED ACCRUAL: A total of 21-48 patients will be accrued for this study within 1-2
Primary Purpose: Treatment
Katherine Warren, MD
National Cancer Institute (NCI)
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|