Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

Phase 1

Completed

• Conditions: Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Neuroblastoma; Unspecified Childhood Solid Tumor, Protocol Specific; Extragonadal Germ Cell Tumor; Sarcoma; Kidney Cancer; Liver Cancer; Ovarian Cancer

• Registration Number: NCT00020150
• Lead Sponsor: National Cancer Institute (NCI)

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.

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.

Study Timeline

• Study Start: 2000-06
• Study First Submitted: 2001-07-11
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Status Verified: 2004-08
• Last Update Submitted: 2015-04-28
• Last Update Posted: 2015-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Trial Locations

Locations (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support; 🇺🇸 Bethesda, Maryland, United States