A Phase I Study Of ZD1839 (Iressa TM), An Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, In Children With Refractory Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- gefitinib
- Conditions
- Unspecified Childhood Solid Tumor, Protocol Specific
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the Common Terminology Criteria (CTC) version 2.0
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
Phase I trial to study the effectiveness of gefitinib in treating children who have refractory solid tumors. Gefitinib may stop the growth of cancer cells by blocking the enzymes necessary for tumor cell growth
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of gefitinib in children with refractory solid tumors. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed solid tumor at original diagnosis
- •Refractory to conventional therapy and other therapies of higher priority according to the COG Phase I/II priority list or no conventional therapy exists
- •No primary CNS tumors or known metastases to the CNS
- •Performance status - Karnofsky 50-100% (over 10 years of age)
- •Performance status - Lansky 50-100% (10 years of age and under)
- •At least 8 weeks
- •Absolute neutrophil count at least 1,000/mm\^3
- •Platelet count at least 50,000/mm\^3 (transfusion independent)
- •Hemoglobin at least 8.0 g/dL (RBC transfusion allowed)
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (gefitinib)
Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Intervention: gefitinib
Treatment (gefitinib)
Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Intervention: pharmacological study
Treatment (gefitinib)
Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the Common Terminology Criteria (CTC) version 2.0
Time Frame: 28 days
DLT defined as hematologic and non-hematologic toxicities toxicities attributable to drug administration occurring during or immediately subsequent to the first course as assessed by CTC version 2.0
Time Frame: 28 days
Pharmacokinetics of gefitinib
Time Frame: At baseline, at 1, 2, 4, 6, 8, 12, and 24 hours after administration, at days 21 and 28, and at day 28 of subsequent courses
Secondary Outcomes
- Antitumor activity of gefitinib according to Response Evaluation Criteria in Solid Tumor (RECIST)(Up to 2 years)