Lapatinib and Trastuzumab With or Without Endocrine Therapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      The neoadjuvant setting is especially attractive for studies of predictive biologic
      correlates for several reasons including early assessment of response to therapy, access to
      the primary tumor, and reduced patient numbers compared to those required in the adjuvant
      setting. Response to neoadjuvant therapy is a validated surrogate marker for improved
      survival; it may be used to test the overall efficacy of neoadjuvant treatment regimens and
      response in the primary tumor mirrors the effect of therapy on micrometastases.

      Trastuzumab is an efficacious agent in HER2 overexpressing breast cancers. Our results with
      neoadjuvant trastuzumab indicate that its efficacy may be better in patients with
      treatment-naïve tumors compared to metastatic disease, with 26% of patients showing a partial
      response after only 3 weeks of therapy. No patients progressed during this 3-week period. We
      have also conducted a neoadjuvant lapatinib study given as a single agent for 6 weeks. The
      response rates in this second study have been impressive with greater than 80% responses in
      patients with HER2 positive locally advanced breast cancers. It is likely that the true
      response rate to HER2 blockade would be higher had therapy been continued for longer. We
      therefore hypothesize that lapatinib, a dual tyrosine kinase inhibitor, together with
      trastuzumab, will result in tumor regression when given as neoadjuvant therapy in HER2
      overexpressing breast cancer. We will compare lapatinib plus trastuzumab for 12 weeks, and if
      the tumors express ER, estrogen deprivation will also be administered.

      This is a phase II trial. Clinical efficacy will be assessed by bidimensional tumor
      measurements of the primary cancer at baseline, and at the end of week 12. Objective tumor
      response rate defined as objective bidimensional tumor measurements after neoadjuvant
      treatment at 12 weeks will be calculated, and assessed according to standard RECIST criteria.
      Pathologic responses will be graded as pathologic complete response if there is no invasive
      cancer in the residual breast at the time of surgery. Near pathologic complete response will
      also be documented as residual disease of less than 1 cm.
    

Intervention name(s): Lapatinib; Trastuzumab; Endocrine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Monoclonal Antibody; Monoclonal Antibody; Hormonal Therapy
Other intervention name(s): TyKerb; Herceptin; Varies
Intervention MeSH terms: Trastuzumab; Lapatinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: primary breast cancers; Locally advanced breast cancers