A Phase I Study of ZD1839 (Iressa) in Combination With Irinotecan (Camptosar or CPT-11) and Vincristine in Pediatric Patients With Refractory Solid Tumors
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
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.
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.
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose limiting toxicities
Within the first 30 days of completion of first cycle
Wayne Furman, M.D.
St. Jude Children's Research Hospital
United States: Food and Drug Administration
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