Docetaxel, Carboplatin, and Trastuzumab and/or Lapatinib in Treating Women With Stage I, Stage II, or Stage III Breast Cancer That Can Be Removed by Surgery
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known
      whether docetaxel and carboplatin are more effective when given together with trastuzumab
      and/or lapatinib in treating women with stage I, stage II, or stage III breast cancer.

      PURPOSE: This randomized phase II trial is studying how well docetaxel and carboplatin work
      when given together with trastuzumab and/or lapatinib in treating women with stage I, stage
      II, or stage III breast cancer that can be removed by surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To investigate the clinical efficacy of neoadjuvant docetaxel and carboplatin in
           combination with trastuzumab (Herceptin®) and/or lapatinib ditosylate by estimating the
           pathologic complete response (pCR) rate in the breast and axilla of women with
           HER2/neu-positive resectable stage I-III adenocarcinoma of the breast.

      Secondary

        -  To estimate the molecular effects of lapatinib ditosylate and trastuzumab alone or in
           combination on tumor tissues of these patients by assessing changes in gene expression
           using serial gene microarray analysis.

        -  To assess for gene expression and/or biomarker changes that may be correlated with or
           predict pCR and clinical response to lapatinib ditosylate and/or trastuzumab in these
           patients.

        -  To evaluate the safety and tolerability of these regimens in these patients.

        -  To evaluate the clinical efficacy of these regimens by estimating the clinical objective
           response rate (complete response and partial response) in these patients.

        -  To estimate the rate of congestive heart failure or drop in LVEF (> 10% points from
           baseline and below lower limits of normal) in each of the three treatment arms.

      OUTLINE: This is a multicenter study. Patients are stratified according to baseline tumor
      size (≤ 3 cm vs > 3 cm) and hormone receptor status (estrogen receptor [ER]- and/or
      progesterone receptor [PR]-positive vs ER- and PR- negative). Patients are randomized to 1 of
      3 treatment arms.

        -  Arm I: Patients receive a trastuzumab IV over 90 minutes on day 1 in course 1. Patients
           receive docetaxel IV, carboplatin IV, and trastuzumab IV over 30 minutes on day 1 in
           courses 2-7. Courses repeat every 21 days in the absence of disease progression or
           unacceptable toxicity.

        -  Arm II: Patients receive oral lapatinib ditosylate once daily on days 1-21 in course 1.
           Patients receive docetaxel IV, carboplatin IV as in arm I and oral lapatinib ditosylate
           once daily on days 1-21 in courses 2-7. Courses repeat every 21 days in the absence of
           disease progression or unacceptable toxicity.

        -  Arm III: Patients receive trastuzumab IV as in arm I on day 1 and oral lapatinib
           ditosylate as in arm II on days 1-21 in course 1. Patients receive docetaxel IV,
           carboplatin IV, and trastuzumab IV as in arm I on day 1 and oral lapatinib ditosylate as
           in arm II on days 1-21 in courses 2-7. Courses repeat every 21 days in the absence of
           disease progression or unacceptable toxicity.

      Within 4-6 weeks after completion of chemotherapy, all patients under go definitive surgery
      and/or radiotherapy at the discretion of the treating physician. Tumor biopsy and blood
      samples are collected for biomarker analysis and molecular analysis at baseline, after course
      1, and at the time of definitive breast surgery or completion of chemotherapy. Gene
      expression changes are analyzed by mRNA microarray analysis and molecular changes in protein
      expression profiles by IHC. Samples may also be analyzed by RT-PCR.
    

Intervention name(s): trastuzumab; carboplatin; docetaxel; lapatinib ditosylate
Intervention type(s): Biological; Drug; Drug; Drug
Intervention description(s): Given IV; Given IV; Given IV; Given orally
Intervention MeSH terms: Carboplatin; Docetaxel; Trastuzumab; Lapatinib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; HER2-positive breast cancer