Trial Information

Phase I/II Study Of Herceptin Combined With OSI-774 In The First-Line Treatment Of Metastatic Breast Cancer Associated With HER2/Neu Overexpression

OBJECTIVES:

- 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
01/2004)

- Determine the safety profile of this regimen in these patients.

- Determine the rate and duration of objective response in patients treated with this
regimen.

- Determine the pharmacologic behavior of this regimen in these patients.

- Determine time to disease progression and duration of survival in patients treated with
this regimen.

- 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
01/2004).

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
this study.