Letrozole In Combination With Lapatinib In Neoadjuvant Treatment Of Early Breast Cancer
Condition: Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: lapatinib; letrozole; placebo
Intervention description: 1500 mg administered orally daily; 2.5 mg administered orally daily; 1500 mg administered orally daily
Intervention MeSH terms: Letrozole; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 92.0
Sex: Female
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: neo-adjuvant; letrozole; lapatinib; primary breast cancer

Summary:

      Evaluate the percentage of clinical objective responses (cOR) in patients with HER2 negative
      early breast cancer treated with pre operative (neoadjuvant)lapatinib and letrozole
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically confirmed infiltrating primary breast cancer of 2.0 cm or more in
             largest clinical diameter

          -  ER and/or PgR positive cancer (> 10% of positive cancer cell assessed by IHC)

          -  Postmenopausal status, defined by at least one of the following:

             ≥ 60 years of age < 60 years of age and amenorrheic for ≥ 12 months prior to day 1 <
             60 years of age and amenorrheic for < 12 months prior to day, or without a uterus:
             luteinizing hormone (LH) and follicle stimulating hormone (FSH) values within
             postmenopausal range Prior bilateral oophorectomy Prior radiation castration with
             amenorrhea for at least 6 months

          -  HER2 negative tumors (IHC 0-2+, or FISH negative)

          -  Availability of tumor tissue suitable for biological and molecular examination before
             starting primary treatment

          -  Age over 18 years

          -  ECOG PS 0-1

          -  Normal organ and marrow function as defined below:

        leukocytes > 3000/mL absolute neutrophil count > 1,500/mL platelets > 100,000/mL total
        bilirubin within normal institutional limits AST (SGOT)/ALT(SGPT)< 2.5 X institutional
        upper limit of normal 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

          -  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 letrozole

          -  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

          -  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
             (See section 3.7.4.2 Other concomitant treatments)