Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells
      and either kill them or deliver tumor-killing substances to them without harming normal
      cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known
      which regimen of chemotherapy plus radiation therapy with or without trastuzumab is more
      effective in treating breast cancer.

      PURPOSE: Randomized phase III trial to compare two different chemotherapy regimens plus
      radiation therapy with or without trastuzumab in treating women who have breast cancer that
      has spread to lymph nodes in the axilla (under the arm).
    

Detailed description: 
      OBJECTIVES:

        -  Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs
           adjuvant docetaxel and epirubicin, in terms of 5-year survival without relapse, in women
           with nonmetastatic adenocarcinoma of the breast with lymph node invasion.

        -  Determine survival of patients treated with these regimens.

        -  Compare the tolerability of trastuzumab (Herceptin) in patients treated with these
           regimens.

        -  Determine the efficacy and tolerability of trastuzumab in patients with hormone
           receptor-positive tumors.

        -  Evaluate the quality of life of patients treated with these regimens.

      OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
      according to participating center. Patients are treated in 2 parts.

        -  Part I: Patients are randomized to 1 of 2 treatment arms.

             -  Arm I: Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV
                on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo
                radiotherapy 5 days a week for 5 weeks.

             -  Arm II: Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour
                on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo
                radiotherapy as in arm I.

      Patients with HER2/neu-positive tumors then proceed to part II. Patients with
      HER2/neu-negative tumors receive no further treatment.

      Patients with hormone (estrogen or progesterone) receptor-positive tumors also receive oral
      tamoxifen daily beginning after chemotherapy is completed and continuing for 5 years.

        -  Part II: Patients are randomized to 1 of 2 treatment arms.

             -  Arm I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes every 3 weeks
                for 1 year.

             -  Arm II: Patients are followed without treatment. Patients not receiving trastuzumab
                are followed at 4 months, 6 months, every 4 months for 1 year, and then every 6
                months for 3 years. Patients receiving trastuzumab are followed at 4 months and
                then every 6 months for 3 years.

      PROJECTED ACCRUAL: A total of 2,600 patients will be accrued for this study within 3 years.
    

Intervention name(s): Trastuzumab; Cyclophosphamide; docetaxel; Epirubicin; Fluorouracil
Intervention type(s): Biological; Drug; Drug; Drug; Drug
Intervention description(s): 8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total); 500 mg/m², D1 and every 3 weeks; on day D1 of each cycle : dose: 75 mg/m², route: i.v. injection over 1 hour, every 3 weeks; 100 mg/m², D1 and every 3 weeks; 500 mg/m², D1 and every 3 weeks
Other intervention name(s): Herceptin; epirubicin hydrochloride
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Fluorouracil; Trastuzumab; Epirubicin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II breast cancer; stage IIIA breast cancer