• To estimate the maximum tolerated dose (MTD) of the intravenous formulation of irinotecan given orally in combination with a fixed dose of oral gefitinib. [ Time Frame: Within the first 30 days of completion of first cycle of chemotherapy. ] [ Designated as safety issue: Yes ]
  

This is a phase I study to estimate the maximum tolerated dose and the dose limiting toxicities of the intravenous formulation of irinotecan given orally in combination with a fixed dose of oral gefitinib. This trial will use the EWOC method, which is an adaptive dose escalation scheme. The method is fully adaptive and makes use of all the information available at the time of each dose assignment, and directly addresses the ethical need to control the probability of overdosing. It is designed to approach the maximum tolerated dose (MTD) as fast as possible.

In this study the intravenous formulation of irinotecan will be given orally on days 1-5 and days 8-12 (dose level begins at 5 mg/m2 ). One patient will be treated at each dose level of irinotecan until moderate toxicity is observed. At the level where moderate toxicity is observed, the cohort size will be increased to 2 patients. Dosages will then be increased until the development of DLT as guided by the EWOC model. The estimated MTD will be continually reassessed using all data from preceding patients. The toxicity data of all patients enrolled in the trial are used to update the dose-toxicity relationship and to guide the next escalation/de-escalation. The calculation will be carried out with EWOC software. Patients will be enrolled and the dose assigned is determined based on previous participants' toxicity. The dose of ZD1839 will be a fixed dose and will be administered orally on days 1-12 - [150 mg/m2 (maximum 250 mg)] Each course of treatment will consist of 21 days. The administration of irinotecan on day 12 of course

1 and day 2 of course 2 will be an intravenous administration. All other doses and subsequent courses will consist of an orally administered dose.

Secondary Objectives Include:

• To describe dose-limiting toxicities (DLTs) of the combination of oral irinotecan and ZD1839 and to define their duration and reversibility.
• To investigate the pharmacokinetics of oral irinotecan and ZD1839 when given in combination in children with recurrent malignant solid tumors.
• To describe the relationship between pharmacokinetic parameters and toxicity.
• To describe any antitumor effects within the confines of a phase I study.
• To examine tumor expression of ErbB1 and/or ABCG2 with respect to pharmacokinetics and response.
• To examine the pharmacogenetic determinants of ZD1839 and irinotecan pharmacokinetics and pharmacodynamics.