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

A Phase 2 Study of Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer

In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying whether positron emission tomography (PET/CT) scans can predict which participants will benefit from the study treatment. Finally, we are studying genes and proteins in the tumor tissue that may lead to sensitivity or resistance to Herceptin, and to the combination of Herceptin plus lapatinib. Lapatinib is a compound that may stop cancer cells from growing. Other research studies suggest that lapatinib in combination with Herceptin may help to shrink or stabilize breast cancer.

• Participants will be asked to undergo a biopsy of an area of the body where the cancer has spread.
• Participants will be given a study medication-dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks during which time you will be taking lapatinib, once per day.
• Participants will receive Herceptin once every week or once every 3 weeks through a vein.
• During all treatment cycles a physical exam will be performed and questions about the participants general health will be asked. Blood tests including chemistry and hematology will be performed to measure additional effect of the study drug and disease status. Photographs may be taken of the tumor to assess the response of the tumor to treatment.
• CT scans will be repeated every 8 weeks to assess the effect of the study treatment on the cancer. Either a MUGA scan or echocardiogram will be performed 8 weeks and 16 weeks after the participant starts the study treatment.
• Participants will remain on this research study for as long as they are benefiting from the study treatment.

Inclusion Criteria:

• 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

Exclusion Criteria:

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