Neoadjuvant Study With Chemotherapy, Lapatinib And Trastuzumab In Breast Cancer
Condition: Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: lapatinib; trastuzumab; paclitaxel; fluorouracil; epidoxorubicin; cyclophosphamide
Intervention description: Arm B 1250mg/d PO Arm C 750mg/d PO; First dose 4mg/kg in 60mins, then weekly 2mg/kg in 30 mins; 80mg/sqm 1 hour infusion for 12 weeks; 600mg/sqm iv day 1 q21 days for four coursess; 75mg/sqm iv day 1 q21 days for four courses; 600mg/sqm day 1 q21 days for four courses
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Fluorouracil; Trastuzumab; Lapatinib; Epirubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 121.0
Sex: Female
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: neo-adjuvant trastuzumab early breast cancer lapatinib

Summary:

      Evaluate the activity of Trastuzumab, Lapatinib, and a combination of both agents with
      chemotherapy in the preoperative (neoadjuvant) treatment of early breast cancer.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically confirmed infiltrating primary breast cancer of > 2.0 cm in largest
             clinical diameter

        HER2 positive tumor (either IHC 3+ or FISH+)

          -  Availability of tumor tissue suitable for biological and molecular examination before
             starting primary treatment

          -  Age >18, < 65 years

          -  ECOG PS 0-1

          -  Normal organ and marrow function as defined below:

        leukocytes ³ 3000/microL

        absolute neutrophil count ³ 1,500/microL

        platelets ³ 100,000/microL

        total bilirubin <= 1.5x ULN. In case of Gilbert's syndrome, <2 x ULN is allowed

        AST (SGOT)/ALT(SGPT)<= 2.5 X institutional upper limit of normal

        Alkaline phosphatase <= 2.5 x ULN

        Creatinine within normal institutional limits

          -  Cardiac ejection fraction within the institutional range of normal as measured by
             echocardiogram or MUGA scan

          -  Eligibility of patients receiving medications or substances known to affect, or with
             the potential to affect the activity or pharmacokinetics of lapatinib will be
             determined following review of their use by the Principal Investigator. A list of
             medications and substances known or with the potential to interact with CYP450
             isoenzymes is provided

          -  The effects of lapatinib on the developing human fetus at the recommended therapeutic
             dose are unknown; women of child-bearing potential must agree to use adequate
             contraception (hormonal or barrier method of birth control or abstinence) prior to
             study entry and for the duration of study participation. Should a woman become
             pregnant or suspect she is pregnant while participating in this study, she should
             inform her treating physician immediately, the patient should be apprised of the
             potential hazard to the fetus and potential risk for loss of the pregnancy

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Ability to swallow and retain oral medication

        Exclusion criteria:

          -  Stage IIIB, IIIC, and inflammatory breast cancer

          -  Stage IV breast cancer

          -  Contraindication to the treatment with anthracycline, paclitaxel and/or trastuzumab

          -  Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment
             with EGFR targeting therapies

          -  Treatment with any other investigational agents, or with all herbal (alternative)
             medicines

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to lapatinib

          -  Uncontrolled inter-current 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

          -  Pregnancy or breastfeeding; (breast feeding should be discontinued to be enrolled in
             the study)

          -  Women of childbearing potential that refusal to adopt adequate contraceptive measures

          -  HIV-positive patients receiving combination anti-retroviral therapy

          -  GI tract disease resulting in an inability to take oral medication, malabsorption
             syndrome, a requirement for IV alimentation, prior surgical procedures affecting
             absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

          -  Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors