A Phase I Study Of ZD1839 (Iressa) In Combination With Irinotecan, Leucovorin, And 5-Fluorouracil In Previously Untreated, Stage IV Colorectal Cancer
I. Determine the maximum tolerated dose of ZD 1839 in combination with irinotecan,
leucovorin calcium, and fluorouracil in patients with locally advanced, locally recurrent,
or metastatic colorectal cancer.
II. Determine the dose-limiting toxicity of this regimen in these patients. III. Determine
the pharmacokinetics of this regimen in these patients. IV. Determine the objective response
rate in patients treated with this regimen.
V. Correlate epidermal growth factor receptor expression with the probability of objective
tumor response in these patients.
OUTLINE: This is a multicenter, dose-escalation study of ZD 1839.
Patients receive oral ZD 1839 daily. Beginning on day 15, patients receive irinotecan IV
over 90 minutes, leucovorin calcium IV over 15 minutes, and fluorouracil IV weekly on weeks
1-2. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable
Cohorts of 3-6 patients receive escalating doses of ZD 1839 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. Once the MTD is determined, 10 additional
patients are accrued to receive treatment at the MTD.
Patients are followed for 30 days.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Charles S. Fuchs, MD
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|