N2003-01: Irinotecan, Temozolomide, and Cefixime in Treating Young Patients With Recurrent or Resistant Neuroblastoma

Neuroblastoma Clinical Trial

Official title: A Phase I Study Of Oral Irinotecan, Temozolomide, Cefixime In Children With Recurrent/Resistant High-Risk Neuroblastoma

Status Completed

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Temozolomide may help irinotecan kill more tumor cells by making them more sensitive to the drug. Cefixime may be effective in preventing diarrhea that is caused by treatment with irinotecan.

PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with temozolomide and cefixime in treating young patients with recurrent or resistant neuroblastoma.

Clinical Trial Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of oral irinotecan when administered with fixed-dose temozolomide and cefixime in pediatric patients with recurrent or resistant high-risk neuroblastoma.

• Determine the toxic effects of this regimen in these patients.

Secondary

• Determine the response rate in patients treated with this regimen.

• Determine the pharmacokinetics of this regimen in these patients.

• Correlate UGT1A1 genotype with the occurrence of dose-limiting diarrhea in patients treated with this regimen.

• Correlate BCRP genotype with pharmacokinetic phenotype in patients treated with this regimen.

• Correlate p53 status in tumor cells with response in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan.

Patients receive oral cefixime once daily beginning 5 days before the start of fixed-dose temozolomide and irinotecan and continuing for the duration of the study. Patients also receive oral temozolomide once daily on days 1-5 and oral irinotecan once daily on days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A maximum of 12 patients are treated at the MTD.

Patients are followed for toxicity, response, and survival.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1.25 years. ;

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diarrhea
• Drug/Agent Toxicity by Tissue/Organ
• Neuroblastoma

• NCT number: NCT00093353
• Study type: Interventional
• Source: Children's Hospital Los Angeles
• Status: Completed
• Phase: Phase 1
• Start date: May 2004