Phase I/II Trial of ZD1839 (Iressa®), Trastuzumab (Herceptin®), and Docetaxel (Taxotere®) in Patients With erbB-2 (HER-2) Overexpressing, Stage IV Breast Carcinoma
- Determine the safety and efficacy of gefitinib, trastuzumab (Herceptin®), and
docetaxel, in terms of time to disease progression, in patients with
HER2/neu-overexpressing metastatic adenocarcinoma of the breast.
- Determine the objective tumor response rate in patients treated with this regimen.
- Correlate expression and/or degree of phosphorylation of epidermal growth factor
receptor, HER2/neu, c-fos, Akt, ERK½, P13K, p53, p21, and p27 with outcome in patients
treated with this regimen.
OUTLINE: This is a phase I, multicenter, dose-escalation study of docetaxel followed by a
phase II study. Patients are stratified according to trastuzumab (Herceptin®)-naive vs
- Phase I: Patients receive oral gefitinib once daily on days 2-14. Patients also receive
trastuzumab* IV over 30-90 minutes and docetaxel IV over 1 hour on day 1. Courses
repeat every 21 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Trastuzumab is given at a higher dose (loading dose) in course 1 and then at a lower
dose in subsequent courses.
Cohorts of 3-6 patients receive docetaxel at dose level 1. If no dose-limiting toxicity
(DLT) is observed in the first cohort of 3 patients, the dose of docetaxel remains the same.
If 1 DLT is observed in the first cohort of 3 patients, 3 additional patients are added (for
a total of 6 patients) to dose level 1. If no further DLTs are observed at dose level 1, the
dose of docetaxel remains the same. If 2 of 3 or 2 of 6 patients experience DLT at dose
level 1, the dose of docetaxel is considered above the maximum tolerated dose (MTD) and is
subsequently reduced. If 2 of 3 or 2 of 6 patients experience DLT at the reduced dose of
docetaxel, the study is stopped.
- Phase II: Patients receive docetaxel at the MTD and gefitinib and trastuzumab as in
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 3-76 patients will be accrued for this study within 26 months.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to progression at 6 months and 1 year
George Somlo, MD
City of Hope Medical Center
United States: Institutional Review Board
|USC/Norris Comprehensive Cancer Center and Hospital||Los Angeles, California 90033-0804|
|City of Hope Comprehensive Cancer Center||Duarte, California 91010|
|City of Hope Medical Group||Pasadena, California 91105|
|Tower Cancer Research Foundation||Beverly Hills, California 90211|
|Hematology Oncology Consultants-Hemet||Hemet, California 92543|
|Breastlink Medical Group, Incorporated at Long Beach Memorial Medical Center||Long Beach, California 90806|