Phase 2 Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer
Condition: Breast Cancer; Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Lapatinib; Doxorubicin; Cyclophosphamide; Docetaxel; Pegfilgrastim; Filgrastim; Dexamethasone; Trastuzumab
Intervention description: 1250 mg, tablets, oral daily during treatment with docetaxel (3-week cycles x 4 cycles); 60 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with cyclophosphamide.; 600 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with doxorubicin.; 100 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide; 6 mg, subcutaneously on day 2 of all cytotoxic chemotherapy treatments.; 300 or 480 mcg, subcutaneously on days 3 to 10 after cytotoxic chemotherapies.; 8 mg, oral taken twice a day for 3 days starting 24 hours before docetaxel; Loading dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks for 1 year
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Docetaxel; Doxorubicin; Trastuzumab; Lapatinib; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: Female
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This trial combines dose dense chemotherapy with doxorubicin and cyclophosphamide (AC)
      followed by standard, every 3 week docetaxel and GW572016 (lapatinib) for neoadjuvant
      treatment of Her2neu positive stage II/III breast cancer. The purpose of the study was to
      determine whether lapatinib combined with chemotherapy was safe and resulted in an increase
      in pathologic complete response rates.
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Female

          -  Histologically-confirmed Her2neu positive breast cancer, by either
             Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization (FISH)+

          -  Stage II/III breast cancer including any large primary tumor (> 2 cm), tumors of any
             size associated with skin or chest wall involvement, tumors of any size with axillary
             lymph node involvement, (T2-T4, N0-N2) and those with ipsilateral subclavicular or
             supraclavicular lymph nodes).

          -  At least one bi-dimensional, measurable indicator lesion.

          -  Between 18 and 70 years of age

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 / Karnofsky ≥ 60% at
             screening and on the first day of treatment.

          -  Informed consent must be obtained prior to registration.

          -  Cardiac ejection fraction within the institutional range of normal as measured by
             multigated acquisition (MUGA) or echocardiography (ECHO) scan.

          -  Absolute neutrophil count > 1,500/mm³

          -  Hemoglobin > 8.0 g/dL

          -  Platelet count > 100,000/mm³

          -  Creatinine within normal institutional limits

          -  Total Bilirubin equal to or less than institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST); alanine aminotransferase (ALT); and alkaline
             phosphatase must be within the range allowing for eligibility. In determining
             eligibility the more abnormal of the two values (AST or ALT) should be used.

          -  Eligibility of patients receiving medications or substances known to affect, or with
             the potential to affect the activity or pharmacokinetics of GW572016 will be
             determined following review of their use by the Principal Investigator

               -  Antacid use is prohibited 1 hour before and 1 hour after GW572016 dosing.

               -  All herbal (alternative) medicines are prohibited.

               -  Medications prohibited during the administration of lapatinib .

          -  Women of child-bearing potential must have negative pregnancy test and 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.

          -  Peripheral neuropathy: must be < grade 1

          -  Able to swallow and retain oral medication

        EXCLUSION CRITERIA

          -  Evidence of disease outside the breast or chest wall, except for ipsilateral axillary
             , supraclavicular, or infraclavicular lymph nodes.

          -  Prior chemotherapy, immunotherapy, or hormonal therapy for breast cancer.

          -  More than 3 months between histologic diagnosis and registration on this study.

          -  History of other malignancy within the last 5years, except curatively treated basal
             cell carcinoma of the skin or carcinoma in situ of the cervix.

          -  Psychological, familial, sociological or geographical conditions which do not permit
             weekly medical follow-up and compliance with the study protocol. Those who are
             medically-unstable, including but not limited to active infection, acute hepatitis,
             deep vein thrombosis requiring anticoagulant therapy, gastrointestinal bleeding,
             uncontrolled hypercalcemia, uncontrolled diabetes, dementia, seizures, superior vena
             cava syndrome, and those whose circumstances do not permit completion of the study or
             the required follow-up.

          -  Congestive heart failure, abnormal left ventricular ejection fraction (LVEF), angina
             pectoris, uncontrolled cardiac arrhythmias, or other significant heart disease, or who
             have had a myocardial infarction within the past year.

          -  Pregnant or lactating

          -  Of childbearing potential and not employing adequate contraception

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to GW572016.

          -  HIV-positive and receiving combination anti-retroviral therapy are excluded from the
             study because of possible pharmacokinetic interactions with lapatinib. Appropriate
             studies will be undertaken in patients receiving combination anti-retroviral therapy
             when indicated.

          -  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).

          -  History of severe hypersensitivity reaction to taxotere or other drugs formulated with
             polysorbate 80.

          -  Current active hepatic or biliary disease (with exception of patients with Gilberts
             syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator
             assessment ).