Lapatinib Ditosylate, Trastuzumab, Paclitaxel, and Surgery in Treating Patients With Breast Cancer
Condition: HER2-positive Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: lapatinib ditosylate; paclitaxel; trastuzumab; therapeutic conventional surgery; pharmacological study; laboratory biomarker analysis
Intervention description: Given PO; Given IV; Given IV; Undergo lumpectomy or mastectomy; Correlative studies; Correlative studies
Intervention MeSH terms: Paclitaxel; Trastuzumab; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: Female
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving lapatinib ditosylate together with trastuzumab,
      paclitaxel, and surgery works in treating patients with breast cancer. Lapatinib ditosylate
      may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
      Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some
      block the ability of tumor to grow and spread. Others find tumor cells and help kill them or
      carry cancer-killing substances to them. Drugs used in chemotherapy, such as paclitaxel, work
      in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed primary invasive breast
             cancer

          -  Primary tumor is larger than 2 cm in diameter (T2) as measured by caliper or
             ultrasound

          -  Overexpression and/or amplification of HER2 is confirmed by immunohistochemistry (IHC)
             3+ or fluorescence in situ hybridization (FISH) + when IHC 2+

          -  Patients have not received prior therapies for breast cancer

          -  Patients have Karnofsky >= 70%

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Hemoglobin >= 9.0 g/dL

          -  Platelets >= 75,000/mcL

          -  Total bilirubin =< 1.5 times institutional upper limit of normal

          -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase[SGPT]) =<
             2.5 times institutional ULN

          -  Creatinine =< 1.5 times institutional upper limit of normal (ULN)

          -  Patients must have left ventricular ejection fraction (LVEF) >= 50% by multi-gated
             acquisition (MUGA) or echocardiography

          -  Patients must be able to take oral medications (i.e., no uncontrolled vomiting,
             inability to swallow, or diagnosis of chronic malabsorption)

          -  Women of childbearing potential must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation as well as for at least 6 months after the last dose of
             trastuzumab

          -  Ability to understand and willingness not only for treatment but also for undergoing
             serial biopsies and sign a written informed consent document

          -  Only Japanese women are eligible for the trial

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy

          -  Patients who are receiving any other investigational agents

          -  Patients have distal metastasis (stage IV disease)

          -  Patients with previous (within 10 years) or current history of malignant neoplasm
             except for curatively treated basal and squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix

          -  Patients with a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to lapatinib or other agents used in study

          -  Patients receiving any medications or substances that are inhibitors or inducers of
             cytochrome P450 3A4 (CYP3A4) are ineligible

          -  Patients who have uncontrolled intercurrent illness including, but not limited to,
             ongoing or active infection, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements

          -  Pregnant women

          -  Patients who have family or personal history of congenital long or short QT syndrome,
             Brugada syndrome, QT/QTc prolongation, or torsade de pointes

          -  Patients who have chronic gastrointestinal disease presenting with diarrhea
             (inflammatory bowel disease, malabsorption, or >= grade 2 diarrhea of any etiology at
             baseline)

          -  Patients who have neuropathy >= grade 2 of any cause

          -  Patients are diagnosed with inflammatory breast cancer or bilateral breast cancer