A Phase I/II Trial of Herceptin and ZD1839 (Iressa, NSC #715055, IND#61187) in Patients With Metastatic Breast Cancer That Overexpresses HER2/Neu (erbB-2)
I. Determine the response rate, duration of response, and time to progression in patients
with metastatic breast cancer that overexpresses HER2-neu treated with trastuzumab
(Herceptin) and gefitinib.
II. Determine the phase II dose of gefitinib when given in combination with trastuzumab in
III. Determine the toxicity of this regimen in these patients. IV. Determine the 3- and
6-month progression-free survival of patients treated with this regimen.
V. Correlate response rates with plasma levels of circulating HER2 and tumor levels of
epidermal growth factor receptor, activated HER2, and HER2 receptors, as measured by
immunohistochemistry and/or fluorescent in situ hybridization (FISH), in patients treated
with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of gefitinib. The phase I portion of
this study was open in only 5 ECOG institutions. The phase I portion has been completed, and
the study is being opened in all ECOG-affiliated institutions.
Phase I (completed): Patients receive trastuzumab (Herceptin) IV over 30-90 minutes once
weekly and oral gefitinib once daily beginning on day 1.
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. Once the MTD is established, additional
patients are accrued to the phase II portion of the study and are treated at that dose.
Phase II: Patients receive oral gefitinib once daily (at the MTD established in phase I) and
trastuzumab IV weekly until week 24, at which time trastuzumab is given every 3 weeks (with
daily gefitinib) until disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until 2 years from
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD and DLT in patients treated with Herceptin and ZD1839 graded using the NCI CTC (Phase I)
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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