Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

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. Combining chemotherapy, monoclonal antibody therapy, and surgery may be a more
      effective treatment for breast cancer.

      PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, monoclonal
      antibody therapy, and surgery in treating women who have stage II, stage III, or stage IV
      breast cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the cardiac and other toxicity of paclitaxel when administered with
           trastuzumab (Herceptin) after doxorubicin and cyclophosphamide in women with stage IIB,
           IIIA, IIIB, IIIC, or previously untreated stage IV breast cancer.

        -  Determine whether the addition of paclitaxel with or without trastuzumab to conventional
           breast cancer adjuvant therapy (doxorubicin and cyclophosphamide) further decreases
           tumor size and the number of positive axillary nodes in these patients.

        -  Determine the 5-year disease-free survival and overall survival of patients treated with
           these regimens.

        -  Determine whether the initial pathologic response in patients receiving neoadjuvant
           therapy correlates with the eventual 5-year disease-free survival or overall survival.

        -  Compare the number of patients eligible for breast-conserving cancer surgery after
           treatment with doxorubicin and cyclophosphamide vs paclitaxel and trastuzumab.

        -  Correlate clinical and radiographic response rate with pathologic response rate in the
           primary tumor and axillary lymph nodes and determine which parameter best determines the
           pathologic response rate in patients treated with these regimens.

      OUTLINE: Patients either received neoadjuvant therapy (HER-2 overexpressing and
      non-overexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).

        -  Neoadjuvant therapy: Patients receive one of two treatment regimens.

             -  Regimen I (HER-2 non-overexpressing patients or HER-2 overexpressing patients who
                refuse trastuzumab (Herceptin) therapy): Patients receive doxorubicin IV and
                cyclophosphamide IV over 30 minutes and paclitaxel IV over 3 hours on day 1 every 3
                weeks for a total of 4 courses. Patients then undergo surgery with or without
                adjuvant radiotherapy and/or oral tamoxifen.

             -  Regimen II (HER-2 overexpressing patients only): Patients receive doxorubicin and
                cyclophosphamide as in regimen I. After completion of course 4, patients receive
                paclitaxel IV and trastuzumab IV over 90-150 minutes weekly on weeks 13-24.
                Patients then undergo surgery with or without adjuvant radiotherapy. Patients then
                receive trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not
                receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.

        -  Adjuvant therapy: Patients who receive adjuvant therapy (HER-2 overexpressing patients
           only) receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 every 3
           weeks for a total of 4 courses. After completion of course 4, patients receive
           paclitaxel IV and trastuzumab IV over 90 minutes weekly on weeks 13-24. Patients then
           may undergo radiotherapy followed by trastuzumab IV over 30 minutes weekly on weeks
           29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive
           radiotherapy.

      Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
      annually for 5 years.

      PROJECTED ACCRUAL: A total of 125 patients (100 in the neoadjuvant group and 25 in the
      adjuvant group) will be accrued for this study within 5 years.
    

Intervention name(s): trastuzumab; cyclophosphamide; doxorubicin hydrochloride; paclitaxel; conventional surgery
Intervention type(s): Biological; Drug; Drug; Drug; Procedure
Intervention description(s): infusion 4 mg/kg load week 1; 2 mg/kg weekly thereafter for 12 weeks; 600 mg/m2, intravenous infusion every 3 weeks for four cycles; 60 mg/m2 intravenously, 5-10 minutes, every 3 weeks, up to 12 weeks; 90 mg/m2 weekly, intravenously 1 hour after herceptin, given weekly up to 12 weeks or 175 mg/m2, intravenously every 3 weeks, up to 12 weeks (only if not receiving Herceptin®); Surgical excision will take place 12-13 weeks for the neo-adjuvant herceptin setting and 12-13 weeks in the non-herceptin setting. Surgery will take place prior to chemotherapy in the adjuvant herceptin setting
Other intervention name(s): Herceptin; Lyophilized Cytoxan; Endoxan; Cytoxan; Neosar; Procytox; Revimmune; Cycloblastin; Adriamycin; Taxol
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Trastuzumab
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II breast cancer; stage IV breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; inflammatory breast cancer