Docetaxel, Carboplatin, Trastuzumab, and Lapatinib in Treating Patients With Early Stage Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: trastuzumab; carboplatin; docetaxel; lapatinib ditosylate
Intervention MeSH terms: Carboplatin; Docetaxel; Trastuzumab; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: male breast cancer; stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer

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. Giving docetaxel together
      with carboplatin, trastuzumab, and lapatinib may kill more tumor cells.

      PURPOSE: This phase II trial is studying the side effects of giving docetaxel together with
      carboplatin, trastuzumab, and lapatinib in treating patients with early stage breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed primary invasive adenocarcinoma of the breast fulfilling the
             following criteria:

               -  Nonmetastatic disease

               -  Operable and adequately excised

                    -  Patients with nonresectable deep margin invasion are eligible provided they
                       have had or will receive radiotherapy to the region

                    -  Patients with histologically documented infiltration of the skin (pT4) are
                       eligible provided they have undergone or will receive radiotherapy
                       encompassing the tumor bed

               -  Node-positive OR -negative and determined eligible to receive adjuvant
                  trastuzumab (Herceptin®)

          -  No positive or suspicious internal mammary nodes by SNS that have not been or will not
             be irradiated

          -  No supraclavicular lymph node involvement (confirmed by fine needle aspiration or
             biopsy)

          -  Over expression and/or amplification of HER2 in the invasive component of the primary
             tumor, according to one of the following:

               -  3+ over-expression by IHC (> 30% of invasive tumor cells)

               -  2+ or 3+ (in 30% or less neoplastic cells) over-expression by IHC AND in situ
                  hybridization (FISH/CISH) test demonstrating HER2 gene amplification

               -  HER2 gene amplification by FISH/CISH (> 6 HER2 gene copies per nucleus, or a FISH
                  ratio [HER2 gene copies to chromosome 17 signals] of > 2.2.)

                    -  Negative or equivocal overall result (FISH test ratio of < 2.2, < 6.0
                       HER2-gene copies per nucleus) and staining scores of 0, 1+, 2+, or 3+ (in
                       30% or less neoplastic cells) by IHC not allowed

          -  Hormone receptor status known (estrogen receptor with or without progesterone
             receptor)

        PATIENT CHARACTERISTICS:

          -  Menopausal status not specified

          -  ECOG performance status 0-1

          -  Hemoglobin ≥ 10.0 g/dL

          -  ANC ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Serum creatinine ≤ 2.0 times upper limit of normal (ULN)

          -  AST and ALT ≤ 2.5 times ULN

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  Bilirubin ≤ 1.5 times ULN (≤ 2.0 times ULN if known Gilbert syndrome)

          -  Baseline LVEF ≥ 50% measured by ECHO or MUGA scan

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No serious cardiac illness or medical condition including, but not limited to, any of
             the following:

               -  History of documented congestive heart failure (any NYHA class) or systolic
                  dysfunction (LVEF < 50%)

               -  High-risk uncontrolled arrhythmias (e.g., ventricular tachycardia, high-grade
                  atrioventricular-block [second degree or higher], or supraventricular arrhythmias
                  that are not adequately rate-controlled)

               -  Angina pectoris requiring antianginal medication

               -  Clinically significant valvular heart disease

               -  Evidence of transmural infarction on ECG

               -  Poorly controlled hypertension (any reading of systolic BP > 180 mm Hg or
                  diastolic BP > 100 mm Hg)

          -  No other concurrent serious diseases that may interfere with planned treatment
             including severe pulmonary conditions or illness

          -  None of the following:

               -  Ulcerative colitis

               -  Malabsorption syndrome

               -  Any disease significantly affecting gastrointestinal function

               -  Inability to swallow oral medication

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior mediastinal irradiation except internal mammary-node irradiation for the
             present breast cancer

          -  No prior anti-HER2 therapy for any reason

          -  No prior biologic or immunotherapy for breast cancer

          -  No prior resection of the stomach or small bowel

          -  No other concurrent anticancer therapy including chemotherapeutic agents, biologic
             agents, or radiotherapy

          -  No concurrent anticancer treatment in another investigational trial with hormone
             therapy or immunotherapy unless approved by the study chair

          -  No concurrent CYP3A4 inhibitors or inducers

          -  No concurrent epoetin alfa, including darbepoetin alfa

          -  No concurrent oprelvekin