Ignite Creation Date:
2025-12-24 @ 5:03 PM
Ignite Modification Date:
2026-01-01 @ 10:09 AM
Study NCT ID:
NCT00020150
Status:
COMPLETED
Last Update Posted:
2015-04-29
First Post:
2001-07-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase I Trial and Pharmacokinetic Study of Temozolomide and O6-Benzylguanine in Childhood Solid Tumors
Status:
COMPLETED
Status Verified Date:
2004-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 children who have solid tumors that have not responded to previous therapy.
PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and O6-benzylguanine in treating children who have solid tumors that have not responded to previous therapy.
Detailed Description:
OBJECTIVES:
* 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 these patients.
* Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in these patients.
* 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 years.
* 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 these patients.
* Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in these patients.
* 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 years.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: