Lapatinib and Trastuzumab With or Without Endocrine Therapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Lapatinib; Trastuzumab; Endocrine
Intervention description: Monoclonal Antibody; Monoclonal Antibody; Hormonal Therapy
Intervention MeSH terms: Trastuzumab; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: Female
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: primary breast cancers; Locally advanced breast cancers

Summary:

      We think that lapatinib will help to shrink your tumor when given prior to the main or
      primary therapy for the kind of breast cancer you have been diagnosed with. When treatment is
      given before the main or primary therapy, it is called neoadjuvant therapy. We will compare
      lapatinib with lapatinib plus trastuzumab (herceptin) for 12 weeks. If your tumor is estrogen
      receptor positive (ER positive), estrogen deprivation will also be given to you. Tumors that
      are ER positive have a lot of estrogen receptors found in them. This is also called "over
      expression" or amplification of estrogen receptors.

      The most important information we will get from this study is to see the response to
      "neoadjuvant" (treatment given before the main treatment), lapatinib with trastuzumab
      (herceptin) in your tumor tissue sample.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must be female.

          -  Signed informed consent.

          -  Locally advanced breast cancers or primary breast cancers are eligible. Locally
             advanced cancers must be of clinical and/or radiologic size >3 cm, or >2 cm with
             clinical evidence of axillary nodal involvement. (If tumors are less than 3 cm, we
             will use radiologically measured tumor size to determine the minimal tumor size for
             eligibility and in assessing tumor size during follow-up).

          -  HER2 overexpressing tumors defined as HercepTest score of 3+, or > 10% cells
             moderately or strongly HER2 positive by other methods, or Allred semi-quantitative
             score of >5, or gene amplified.

          -  Negative serum pregnancy test (HCG) within 7 days of starting study, if of
             child-bearing potential.

          -  Kidney and liver function tests - all within 1.5 times the institution's upper limit
             of normal.

          -  Performance status (WHO scale) less than 2 and life expectancy more than 6 months.

          -  Age at least 18 years.

          -  No brain or leptomeningeal disease.

          -  No previous or current malignancies at other sites within the last 5 years, with
             exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri
             and basal or squamous cell carcinoma of the skin.

        Note: The presence of pathological involvement of axillary nodes will be assessed and
        agreed upon by two investigators.

        Exclusion Criteria:

          -  Pregnancy or unwillingness to use a reliable contraceptive method in women of
             child-bearing potential.

          -  Severe underlying chronic illness or disease.

          -  Cardiomyopathy or baseline LVEF less than 50%.

          -  Other investigational drugs while on study.

          -  Severe or uncontrolled hypertension, history of congestive heart failure or severe
             coronary arterial disease.

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel. Subjects with ulcerative colitis are also
             excluded

          -  Taking any lapatinib-prohibited medication within 7 days of first dose of study
             medications. (See Prohibited Medications List in protocol.)