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)
Cancer Care Center at Northside Medical Center
🇺🇸Youngstown, Ohio, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Helen and Harry Gray Cancer Center at Hartford Hospital
🇺🇸Hartford, Connecticut, United States
CCOP - Christiana Care Health Services
🇺🇸Wilmington, Delaware, United States
Hopital du Saint-Sacrement, Quebec
🇨🇦Quebec City, Quebec, Canada
Cancer Research Center at Boston Medical Center
🇺🇸Boston, Massachusetts, United States
CCOP - Virginia Mason Research Center
🇺🇸Seattle, Washington, United States
Comprehensive Cancer Institute
🇺🇸Huntsville, Alabama, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
CCOP - Santa Rosa Memorial Hospital
🇺🇸Santa Rosa, California, United States
Phoebe Cancer Center at Phoebe Putney Memorial Hospital
🇺🇸Albany, Georgia, United States
Genesis Regional Cancer Center at Genesis Medical Center
🇺🇸Davenport, Iowa, United States
Community Hospital
🇺🇸Munster, Indiana, United States
UMASS Memorial Cancer Center - University Campus
🇺🇸Worcester, Massachusetts, United States
Cancer Research Network, Inc.
🇺🇸Plantation, Florida, United States
Berkshire Medical Center
🇺🇸Pittsfield, Massachusetts, United States
CCOP - Grand Rapids
🇺🇸Grand Rapids, Michigan, United States
MBCCOP-Medical College of Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
CCOP - Central Illinois
🇺🇸Decatur, Illinois, United States
Kaiser Permanente Medical Center - Vallejo
🇺🇸Vallejo, California, United States
Morton Plant Hospital
🇺🇸Clearwater, Florida, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Providence Cancer Institute at Providence Hospital - Southfield Campus
🇺🇸Southfield, Michigan, United States
Sutter Health Western Division Cancer Research Group
🇺🇸Greenbrae, California, United States
Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
🇺🇸Baltimore, Maryland, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Creticos Cancer Center at Advocate Illinois Masonic Medical Center
🇺🇸Chicago, Illinois, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia
🇺🇸Columbia, Missouri, United States
CCOP - Illinois Oncology Research Association
🇺🇸Peoria, Illinois, United States
CCOP - Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
Dwight David Eisenhower Army Medical Center
🇺🇸Fort Gordon, Georgia, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
CCOP - Duluth
🇺🇸Duluth, Minnesota, United States
William Beaumont Hospital - Royal Oak
🇺🇸Royal Oak, Michigan, United States
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
🇺🇸Syracuse, New York, United States
Royal Victoria Hospital - Montreal
🇨🇦Montreal, Quebec, Canada
Montreal General Hospital
🇨🇦Montreal, Quebec, Canada
Charles R. Wood Cancer Center at Glens Falls Hospital
🇺🇸Glens Falls, New York, United States
CCOP - Columbus
🇺🇸Columbus, Ohio, United States
Carlo Fidani Peel Regional Cancer Centre at Credit Valley Hospital
🇨🇦Mississauga, Ontario, Canada
Centre Hospitalier de l'Universite de Montreal
🇨🇦Montreal, Quebec, Canada
Jewish General Hospital - Montreal
🇨🇦Montreal, Quebec, Canada
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
St. Mary's Hospital Center
🇨🇦Montreal, Quebec, Canada
CCOP - Northwest
🇺🇸Tacoma, Washington, United States
CCOP - Southern Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Methodist Cancer Center at Methodist Hospital
🇺🇸Indianapolis, Indiana, United States
Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
🇺🇸San Diego, California, United States
Hennepin County Medical Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Cancer Center at Jewish Hospital
🇺🇸Cincinnati, Ohio, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Charles M. Barrett Cancer Center at University Hospital
🇺🇸Cincinnati, Ohio, United States
CCOP - Wichita
🇺🇸Wichita, Kansas, United States
CCOP - Western Regional, Arizona
🇺🇸Phoenix, Arizona, United States
University of Colorado Cancer Center at University of Colorado Health Sciences Center
🇺🇸Denver, Colorado, United States
CCOP - Colorado Cancer Research Program, Incorporated
🇺🇸Denver, Colorado, United States
Josephine Ford Cancer Center at Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, 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
CCOP - Bay Area Tumor Institute
🇺🇸Oakland, California, United States
Pacific Shores Medical Group Comprehensive Hematology-Oncology Services - Long Beach
🇺🇸Long Beach, California, United States
Comprehensive Cancer Center at Desert Regional Medical Center
🇺🇸Palm Springs, California, United States
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
🇺🇸Orange, California, United States
North Idaho Cancer Center
🇺🇸Coeur d'Alene, Idaho, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
CancerCare of Maine at Eastern Maine Medial Center
🇺🇸Bangor, Maine, United States
Baystate Regional Cancer Program at D'Amour Center for Cancer Care
🇺🇸Springfield, Massachusetts, United States
Missouri Baptist Cancer Center
🇺🇸Saint Louis, Missouri, United States
CCOP - Cancer Research for the Ozarks
🇺🇸Springfield, Missouri, United States
Saint Louis University Cancer Center
🇺🇸Saint Louis, Missouri, United States
CCOP - St. Louis-Cape Girardeau
🇺🇸Saint Louis, Missouri, United States
CCOP - Montana Cancer Consortium
🇺🇸Billings, Montana, United States
CCOP - Northern New Jersey
🇺🇸Hackensack, New Jersey, United States
Nalitt Cancer Institute at Staten Island University Hospital
🇺🇸Staten Island, New York, United States
Alamance Cancer Center
🇺🇸Burlington, North Carolina, United States
Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital
🇺🇸Greenville, North Carolina, United States
CCOP - Merit Care Hospital
🇺🇸Fargo, North Dakota, United States
Akron City Hospital at Summa Health System
🇺🇸Akron, Ohio, United States
Aultman Hospital Cancer Center at Aultman Health Foundation
🇺🇸Canton, Ohio, United States
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
South Pointe Hospital Cancer Care Center
🇺🇸Cleveland, Ohio, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
🇺🇸Columbus, Ohio, United States
CCOP - Dayton
🇺🇸Kettering, Ohio, United States
CCOP - Oklahoma
🇺🇸Tulsa, Oklahoma, United States
CCOP - Columbia River Oncology Program
🇺🇸Portland, Oregon, United States
John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Albert Einstein Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Mercy Hospital Cancer Center - Scranton
🇺🇸Scranton, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Hillman Cancer Center at University of Pittsburgh Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
York Cancer Center at Wellspan Health
🇺🇸York, Pennsylvania, United States
Kent County Memorial Hospital
🇺🇸Warwick, Rhode Island, United States
CCOP - Greenville
🇺🇸Greenville, South Carolina, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
CCOP - Upstate Carolina
🇺🇸Spartanburg, South Carolina, United States
CCOP - Sioux Community Cancer Consortium
🇺🇸Sioux Falls, South Dakota, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Utah Valley Regional Medical Center - Provo
🇺🇸Provo, Utah, United States
Vermont Cancer Center at University of Vermont
🇺🇸Burlington, Vermont, United States
Sentara Cancer Institute at Sentara Norfolk General Hospital
🇺🇸Norfolk, Virginia, United States
Puget Sound Oncology Consortium
🇺🇸Seattle, Washington, United States
David Lee Cancer Center at Charleston Area Medical Center
🇺🇸Charleston, West Virginia, United States
Camden-Clark Memorial Hospital
🇺🇸Parkersburg, West Virginia, United States
St. Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
CCOP - Marshfield Clinic Research Foundation
🇺🇸Marshfield, Wisconsin, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
National Naval Medical Center
🇺🇸Bethesda, Maryland, United States
Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
🇺🇸Omaha, Nebraska, United States
CCOP - Missouri Valley Cancer Consortium
🇺🇸Omaha, Nebraska, United States
Oncology Alliance, S.C. - Milwaukee
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Sutter Cancer Center
🇺🇸Sacramento, California, United States
CCOP - Michigan Cancer Research Consortium
🇺🇸Ann Arbor, Michigan, United States
CCOP - Southeast Cancer Control Consortium
🇺🇸Winston-Salem, North Carolina, United States
Comprehensive Cancer Center at Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
Halifax Medical Center
🇺🇸Daytona Beach, Florida, United States
John H. Stroger, Jr. Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Baptist Cancer Institute - Jacksonville
🇺🇸Jacksonville, Florida, United States
CCOP - Atlanta Regional
🇺🇸Atlanta, Georgia, United States
New York Oncology Hematology, P.C. at Albany Regional Cancer Care
🇺🇸Albany, New York, United States
Rush Cancer Institute at Rush University Medical Center
🇺🇸Chicago, Illinois, United States
CCOP - Northern Indiana CR Consortium
🇺🇸South Bend, Indiana, United States
CCOP - Evanston
🇺🇸Evanston, Illinois, United States
West Suburban Hospital Medical Center
🇺🇸Oak Park, Illinois, United States
Michigan State University
🇺🇸East Lansing, Michigan, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
University of New Mexico Cancer Research and Treatment Center
🇺🇸Albuquerque, New Mexico, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
M.D. Anderson Cancer Center - Orlando
🇺🇸Orlando, Florida, United States
CCOP - Ochsner
🇺🇸New Orleans, Louisiana, United States
Tulane Cancer Center at Tulane University Hospital and Clinic
🇺🇸New Orleans, Louisiana, United States
CCOP - Kansas City
🇺🇸Kansas City, Missouri, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Norton Cancer Center at Norton Hospital
🇺🇸Louisville, Kentucky, United States
Consultants in Blood Disorders and Cancer
🇺🇸Louisville, Kentucky, United States
Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans
🇺🇸New Orleans, Louisiana, United States
MBCCOP - Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Cancer Research Center of Hawaii
🇺🇸Honolulu, Hawaii, United States
CCOP - Iowa Oncology Research Association
🇺🇸Des Moines, Iowa, United States
Lincoln Medical and Mental Health Center
🇺🇸Bronx, New York, United States
MBCCOP-Our Lady of Mercy Cancer Center
🇺🇸Bronx, New York, United States