Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Lapatinib; Herceptin
Intervention MeSH terms: Trastuzumab; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER2-positive breast cancer; Herceptin; trastuzumab

Summary:

      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.
    

Eligibility criteria:

        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