Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00004067
- Lead Sponsor
- NSABP Foundation Inc
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, 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. It is not yet known whether combination chemotherapy plus trastuzumab is more effective than combination chemotherapy alone for treating breast cancer.
PURPOSE: This randomized phase III trial is studying how well giving combination chemotherapy together with trastuzumab works compared to combination chemotherapy alone in treating women with node-positive stage II or stage IIIA breast cancer that overexpresses HER2.
- Detailed Description
OBJECTIVES:
* Compare the cardiotoxicity of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab (Herceptin®) in women with operable, node-positive breast cancer that overexpresses HER2.
* Compare the effect of these regimens on disease-free and overall survival of these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (1-3 vs 4-9 vs 10 or more), administration of hormonal therapy (tamoxifen vs anastrozole vs neither), surgery/radiotherapy (lumpectomy plus breast irradiation vs lumpectomy plus breast irradiation plus regional irradiation vs mastectomy without radiotherapy vs mastectomy with radiotherapy), paclitaxel schedule (every 3 weeks vs weekly), and participating center. Patients are randomized to one of two treatment arms.
* Arm 1: Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses. Approximately 3 weeks after the last course, patients receive paclitaxel IV over 3 hours every 21 days for 4 courses OR paclitaxel IV over 1 hour once weekly for 12 weeks (12 doses).
* Arm 2: Patients receive chemotherapy as in arm I and trastuzumab (Herceptin®) IV over 90 minutes on day 1 of the first course of paclitaxel. Trastuzumab is then administered IV over 30 minutes weekly for 51 weeks, beginning on day 8.
All patients with estrogen or progesterone receptor-positive tumors receive hormonal therapy\* for at least 5 years, beginning within 3-12 weeks after the last dose of chemotherapy. Patients who have received prior tamoxifen for prevention may be treated with additional tamoxifen for no more than 5 years at the discretion of the principal investigator (PI).
NOTE: \*Other hormonal therapeutic agents are allowed in sequence with or as an alternative to tamoxifen therapy.
All patients previously treated with lumpectomy undergo breast irradiation beginning after completion of chemotherapy and concurrently with trastuzumab (in arm 2) administration. Patients previously treated with mastectomy may also receive radiotherapy. Radiotherapy is administered daily for 5-6 weeks.
Patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 2,700 patients will be accrued for this study within 4.75 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 2130
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2: adriamycin + cyclophosphamide then taxol + herceptin herceptin - Arm 1: adriamycin + cyclophosphamide then taxol adriamycin - Arm 1: adriamycin + cyclophosphamide then taxol cyclophosphamide - Arm 1: adriamycin + cyclophosphamide then taxol taxol - Arm 2: adriamycin + cyclophosphamide then taxol + herceptin adriamycin - Arm 2: adriamycin + cyclophosphamide then taxol + herceptin cyclophosphamide - Arm 2: adriamycin + cyclophosphamide then taxol + herceptin taxol -
- Primary Outcome Measures
Name Time Method Disease Free Survival (DFS) Time from randomization through 5 years Breast cancer recurrence, second primary cancer, death from any cause as first event
Cardiotoxicity time from randomization through 4 months
- Secondary Outcome Measures
Name Time Method Survival time from randomization through 5 years Death from any cause.
Long term effect of trastuzumab on cardiac function At 5 and 10 years after randomization Ejection fraction will be measured by multigated acquisition scan (MUGA).
Trial Locations
- Locations (149)
Comprehensive Cancer Institute
🇺🇸Huntsville, Alabama, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
CCOP - Western Regional, Arizona
🇺🇸Phoenix, Arizona, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Sutter Health Western Division Cancer Research Group
🇺🇸Greenbrae, California, United States
Scripps Cancer Center at Scripps Clinic
🇺🇸La Jolla, California, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Pacific Shores Medical Group Comprehensive Hematology-Oncology Services - Long Beach
🇺🇸Long Beach, California, United States
CCOP - Bay Area Tumor Institute
🇺🇸Oakland, California, United States
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
🇺🇸Orange, California, United States
Scroll for more (139 remaining)Comprehensive Cancer Institute🇺🇸Huntsville, Alabama, United States