Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Biological: trastuzumabProcedure: conventional surgery
- Registration Number
- NCT00006110
- Lead Sponsor
- UNC Lineberger Comprehensive Cancer Center
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 82
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Neo-adjuvant Herceptin with or without radiation trastuzumab Chemotherapy followed by Taxol plus Herceptin followed by surgery followed by radiation (or no radiation) followed by additional Herceptin Non-Herceptin with or without radiation doxorubicin hydrochloride Chemotherapy followed by Taxol followed by surgery followed by radiation (or no radiation) Neo-adjuvant Herceptin with or without radiation cyclophosphamide Chemotherapy followed by Taxol plus Herceptin followed by surgery followed by radiation (or no radiation) followed by additional Herceptin Non-Herceptin with or without radiation conventional surgery Chemotherapy followed by Taxol followed by surgery followed by radiation (or no radiation) Neo-adjuvant Herceptin with or without radiation conventional surgery Chemotherapy followed by Taxol plus Herceptin followed by surgery followed by radiation (or no radiation) followed by additional Herceptin Non-Herceptin with or without radiation paclitaxel Chemotherapy followed by Taxol followed by surgery followed by radiation (or no radiation) Neo-adjuvant Herceptin with or without radiation doxorubicin hydrochloride Chemotherapy followed by Taxol plus Herceptin followed by surgery followed by radiation (or no radiation) followed by additional Herceptin Neo-adjuvant Herceptin with or without radiation paclitaxel Chemotherapy followed by Taxol plus Herceptin followed by surgery followed by radiation (or no radiation) followed by additional Herceptin Non-Herceptin with or without radiation cyclophosphamide Chemotherapy followed by Taxol followed by surgery followed by radiation (or no radiation)
- Primary Outcome Measures
Name Time Method Cardiac Toxicity of Weekly Taxol Given With Weekly Herceptin When Delivered Immediately Following Four Cycles of Standard Dose AC. 78 weeks (1.5 years) Doxorubicin + cyclophosphamide in combination with paclitaxel and trastuzumab (AC-TP) Associated Systolic Dysfunction. Systolic function was measured by the ventricular ejection fraction (LVEF). LVEF is a measurement in determining how well your heart is pumping out blood and in diagnosing and tracking heart failure.
- Secondary Outcome Measures
Name Time Method Overall Response 78 weeks (1.5 years) Measured by the Overall Response. Response: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Disease-free Survival (DFS) in Patients Receiving and Not Receiving Herceptin®. 5 years Percent of patients receiving and not receiving Herceptin who are alive and disease-free at 5 years.
Trial Locations
- Locations (2)
Comprehensive Cancer Center at Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States