NCT00186979

Study of ZD1839 Combined With Irinotecan and Vincristine in Pediatric Patients With Refractory Solid Tumors

A Phase I Study of ZD1839 (Iressa) in Combination With Irinotecan (Camptosar or CPT-11) and Vincristine in Pediatric Patients With Refractory Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this protocol is to estimate the maximum tolerated dose of gefitinib in combination with fixed dose of irinotecan and vincristine in patients with refractory solid tumors.

Detailed description

Objectives of this study are: * To determine the dose-limiting toxicities (DLT) of the combination of irinotecan and ZD1839 when given on this schedule. * To characterize the pharmacokinetics and pharmacodynamics of gefitinib alone and in combination with irinotecan and vincristine. * To estimate the maximum tolerated dose (MTD) of gefitinib in combination with escalating intravenous irinotecan by using selective intestinal decontamination with oral cefixime or cefpodoxime to prevent diarrhea. * To estimate the MTD of vincristine (MTD) in combination with gefitinib and irinotecan. Details of Treatment Interventions First Cohort: Standard dose escalation, starting at ZD1839 150 mg/m2/day for 21 days in combination with irinotecan 15mg/m2/day on a daily x 5 for two consecutive week schedule. Dose-limiting diarrhea was seen in this cohort. ZD scheduled was reduced to 12 days. The first dose level (1a) consisted of ZD1839 112.5mg/m2/day for 12 days + irinotecan 15mg/m2/day daily x 5 x 2 and was found to be the MTD in this cohort. Second Cohort: Cefixime then added at 4 additional subjects were enrolled at dose level 1c, consisting of ZD1839 at 112mg/m2/day + irinotecan 20mg/m2/day + cefixime 8 mg/kg/day administered once daily, beginning on day -1, and continued to day 14. Third Cohort: Irinotecan/ZD1839/Vincristine/Cefixime- Cefixime 8 mg/kg/day administered once daily, beginning on day -1, and continued to day 14, with a maximum dose of 400 mg daily + gefitinib 112.5 mg/m2 orally, daily for 12 days and irinotecan at 15 mg/m2 daily x 5 x 2 +1 mg/m2 (maximum 2mg/dose) on days 1 and 8 with escalating dose of VCR as tolerated.

Conditions

• Solid Tumors

Interventions

Type	Name	Description
DRUG	Irinotecan, ZD1839, Vincristine, Cefixime, Cefpodoxime.	See Detailed Description section for details of treatment interventions.

Timeline

• Start date: 2003-05-01
• Primary completion: 2010-03-01
• Completion: 2010-03-01
• First posted: 2005-09-16
• Last updated: 2017-04-26

Locations

1 site across 1 country: United States