A Phase I Study Of ZD1839 (Iressa TM), An Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, In Children With Refractory Solid Tumors
I. Determine the maximum tolerated dose of gefitinib in children with refractory solid
II. Determine the dose-limiting toxicity of this drug in these patients. III. Determine the
pharmacokinetics of this drug in these patients. IV. Determine, preliminarily, the antitumor
activity of this drug in these patients.
V. Correlate the pharmacogenetic polymorphisms of this drug with pharmacokinetics and
pharmacodynamics in these patients.
OUTLINE: This is a dose-escalation, multicenter study. If myelosuppression is found to be
the dose-limiting toxicity, patients are stratified according to prior therapy (more than 2
multiagent chemotherapy regimens or radiotherapy to more than 20% of the bone marrow or stem
cell transplantation with or without total body irradiation vs more than 2 single-agent
phase I or phase II agents) and extent of disease (bone marrow involvement vs meeting none
of the stratum I criteria).
Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of gefitinib 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.
PROJECTED ACCRUAL: Approximately 3-45 patients will be accrued for this study.
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the Common Terminology Criteria (CTC) version 2.0
Children's Oncology Group
United States: Food and Drug Administration
|Children's Oncology Group||Arcadia, California 91006-3776|