RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill
them or deliver tumor-killing substances to them without harming normal cells. Biological
therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth
of the tumor. Combining trastuzumab with erlotinib may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with erlotinib
as first-line therapy in treating women who have metastatic breast cancer associated with
- Determine the maximum tolerated dose and recommended phase II dose of erlotinib when
combined with trastuzumab (Herceptin) as first-line therapy in women with metastatic
breast cancer associated with HER2/neu overexpression. (Phase I closed to accrual as of
- Determine the safety profile of this regimen in these patients.
- Determine the rate and duration of objective response in patients treated with this
- Determine the pharmacologic behavior of this regimen in these patients.
- Determine time to disease progression and duration of survival in patients treated with
- Correlate the antitumor activity of this regimen with epidermal growth factor receptor
expression in these patients.
OUTLINE: This is a dose-escalation study of erlotinib. (Phase I closed to accrual as of
Patients receive oral erlotinib once daily beginning on day 2 and trastuzumab (Herceptin) IV
over 30-90 minutes (1-4 hours after erlotinib) once weekly beginning on day 1. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib 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, additional
patients are treated at the recommended phase II dose.
Patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for the phase I portion (closed
to accrual as of 01/2004) and 27-81 patients will be accrued for the phase II portion of
- Women aged > 18 years
- Histologically documents metastatic breast cancer
- HER2 positive using FISH
- For phase I, patients who have previously received treatment for their metastatic
disease are allowed to participate.
- For the phase II portion of the study, patients must have measureable disease (> 2
cm; > 1 cm on spiral CT scan)
- ECOG performance status of 0 to 2
- A life expectancy of > 3 months
- Use of effective means of contraception
- For Phase II, prior cytotoxic chemotherapy and/or prior Herceptin for their
metastatic disease. Prior treatment in the adjuvant setting is allowed.