Phase II Neoadjuvant in Inflammatory Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Inflammatory Breast Neoplasms
Intervention: Lapatinib; Paclitaxel; 5-Fluorouracil (5-FU); Epirubicin; Cyclophosphamide
Intervention description: 1000 mg taken by every day by mouth (PO) weeks 1 and 2; then starting day 15 for 12 weeks (weeks 3 to 14) daily 750 mg PO. Week 15, second combination treatment consisting of lapatinib (1,000 mg orally once daily) combined with FEC7.; 80 mg/m^2 intravenously over 1 hour weekly for 4 cycles administered on Day 1, Day 8, and Day 15 of each cycle then weekly starting day 15 for 12 weeks.; 500 mg/m^2 intravenously over 3-5 minutes every three weeks of Weeks 13-24.; 75 mg/m^2 intravenously over 5-10 minutes every three weeks of Weeks 13-24.; 500 mg/m^2 intravenously over 45-60 minutes every three weeks of Weeks 13-24.
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Fluorouracil; Epirubicin; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer; Inflammatory Breast Cancer; IBC; ErbB2 overexpression; Lapatinib; Paclitaxel; 5-Fluorouracil; Epirubicin; Cyclophosphamide; Neoadjuvant Chemotherapy

Summary:

      The goal of this clinical research study is to learn how well lapatinib taken alone, followed
      by taking lapatinib with paclitaxel, and then taking lapatinib with 5-fluorouracil,
      epirubicin, and cyclophosphamide (FEC75) works to help to control Inflammatory Breast Cancer
      (IBC). The safety of this drug combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have signed informed consent form (ICF) and a Patient Authorization Form (HIPAA).

          2. Histological confirmation of breast carcinoma with a clinical diagnosis of IBC based
             on the presence of inflammatory changes in the involved breast, including diffuse
             erythema and edema (peau d'orange), with or without an underlying palpable mass,
             involving the majority of the skin of the breast. Pathologic evidence of dermal
             lymphatic invasion should be noted but is not required for diagnosis.

          3. Tumors that overexpress ErbB2, defined as one of the following definitions: 3+
             staining by immunohistochemistry and/or a FISH ratio of more than 2.2

          4. Have either measurable or clinically evaluable skin disease. Patients with metastasis
             but are candidates for mastectomy are eligible.

          5. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 - 1.

          6. Have left ventricular ejection fraction (LVEF) within the institutional range of
             normal as measured by either echocardiogram (ECHO) or MUGA scans. The same modality
             must be used consistently throughout the study.

          7. Willing to under go 1 mandatory core biopsy (up to 4 passes) and 1 mandatory skin
             biopsy to confirm IBC diagnosis and for biologic expression profiling.Subjects with
             clinically palpable residual disease may undergo an optional 2nd and 3rd core needle
             biopsy (1 after initial 2-week Lapatinib therapy and 1 after 6 months of completing
             all chemotherapy, before surgery) to allow identification of presumed pathways of
             therapy resistance. Information may give subject options for other targeted therapies
             (e.g. trastuzumab) if definitive surgery confirms residual disease.

          8. Are able to swallow and retain oral medication (intact pill).

          9. Are able to complete all screening assessments as outlined in the protocol.

         10. Have adequate organ function.

         11. Are subjects aged >/= 18 years with any menopausal status: Non-child-bearing potential
             (i.e., women with functioning ovaries who have a current documented tubal ligation or
             hysterectomy, or women who are postmenopausal) Child-bearing potential (i.e., women
             with functioning ovaries and no documented impairment of oviductal or uterine function
             that would cause sterility.) This category includes women with oligomenorrhea
             (severe), women who are perimenopausal, and young women who have begun to menstruate.
             Criterion continued in #13

         12. These subjects must have a negative serum pregnancy test at screening and agree to one
             of the following: Complete abstinence from intercourse from 2 weeks prior to
             administration of the first dose of study medication until 28 days after the final
             dose of study medication; or Consistent and correct use of one of the following
             acceptable methods of birth control: male partner who is sterile prior to the female
             subject's entry into the study and is the sole sexual partner for that female subject;
             Criterion continued in # 13

         13. Any intrauterine device (IUD) with a documented failure rate of less than 1% per year;
             oral contraceptives (either combined or progestogen only) where not contraindicated
             for this subject population or per local practice.; or barrier methods, including
             diaphragm or condom with a spermicide. Please note that breast cancer subjects on this
             trial cannot receive injectable levonorgestrel or injectable progestogen due to the
             potential for an adverse effect of anti-hormonal therapies on chemotherapy
             administered for breast cancer.

        Exclusion Criteria:

          1. Have received any prior to chemotherapy.

          2. Had prior therapy with an ErbB1 and/or ErbB2 inhibitor.

          3. Are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, and
             biologic therapy) while taking study medication.

          4. Have Malabsorption syndrome, disease significantly affecting gastrointestinal
             function, or resection of the stomach or small bowel. Women with ulcerative colitis
             are also excluded.

          5. Have a concurrent disease or condition that would make the woman inappropriate for
             study participation, or any serious medical disorder that would interfere with the
             woman's safety.

          6. Have an active or uncontrolled infection.

          7. Have dementia, altered mental status, or any psychiatric condition that would prohibit
             the understanding or rendering of informed consent.

          8. Have active cardiac disease, defined as one or more of the following: history of
             uncontrolled of symptomatic angina, history of arrhythmias requiring medications, or
             clinically significant; myocardial infarction < 6 months from study entry;
             uncontrolled or symptomatic congestive heart failure; ejection fraction below the
             institutional normal limit; any other cardiac condition, which is in the opinion of
             the treating physician, would make this protocol unreasonably hazardous for the
             patient

          9. Are pregnant or breastfeeding.

         10. Have received concurrent treatment with an investigational agent clinical trial.

         11. Use of any prohibited medications concurrently with lapatinib therapy.

         12. Have used investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of study medication.

         13. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to any of the agents used in this study or their excipients.

         14. Are receiving therapeutic anti-coagulation therapy (i.e. warfarin, heparin)