Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer

Prior treatment

• Patients may not be receiving any other investigational agents or concurrent chemotherapy or hormonal therapy for treatment of metastatic disease
• Concurrent use of the medications listed in the protocol because of possible interaction with lapatinib

Other illness

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or other agents used in this study
• Clinically significant malabsorption syndrome
• Uncontrolled intercurrent illness

Other

• Active brain metastases
• Pregnant or breastfeeding women

• Histologically or cytologically confirmed invasive breast cancer, with stage IV disease
• HER2-positive breast cancer, defined as 3+ staining by IHC or gene amplification by FISH
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
• Willingness to undergo a research biopsy of recurrent or metastatic disease
• Prior chemotherapy treatment must be discontinued for at least 2 weeks prior to study entry.
• Completed radiation therapy at least 7 days prior to beginning protocol treatment
• Cohort 1: No prior chemotherapy for advanced breast cancer; no prior trastuzumab in the advanced breast cancer setting; nor prior treatment with lapatinib or other HER2-directed therapy other than trastuzumab
• Cohort 2: Up to two prior chemotherapy regimens for the treatment of advanced breast cancer; no prior treatment with lapatinib or other HER2-directed therapy except for trastuzumab
• 18 years of age or older
• Life expectancy of greater than 12 weeks
• ECOG Performance Status 0-2
• Normal organ and marrow function as outlined in protocol
• Cardiac ejection fraction, as assessed by either MUGA scan or echocardiogram greater than or equal to 50%
• Able to take oral medications