The primary purpose of this study is to determine whether breast cancer tumors respond (as
measured by pathologic complete response: the absence of microscopic evidence of invasive
tumor cells in the breast) to combined chemotherapy of AC(doxorubicin and cyclophosphamide)
followed by paclitaxel plus trastuzumab or lapatinib or both given before surgery to
patients with HER2-positive breast cancer. Trastuzumab will also be given to all patients
after surgery. The study will also evaluate the toxic effects of the chemotherapy
combination, including effects on the heart, and will determine survival and
progression-free survival 5 years after treatment. Also, the study will look at whether
there are gene expression profiles in the tumor tissue that can predict pathologic complete
response.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Inclusion criteria:
- Female
- 18 years or older
- ECOG performance status of 0 or 1
- Primary breast tumor palpable and measures greater than or equal to 2. 0 cm by
physical exam
- Diagnosis of invasive adenocarcinoma made by core needle biopsy
- Breast cancer determined to be HER2-positive
- LVEF assessment by MUGA scan or ECG within 3 months prior to randomization
- Blood counts must meet the following criteria:
- ANC greater than or equal to 1200/mm3
- Platelet count greater than or equal to 100,000/mm3
- Hemoglobin greater than or equal to 10 g/dL
- Serum creatinine less than or equal to ULN for the lab
- Adequate hepatic function by these criteria:
- Total bilirubin less than or equal to the ULN for the lab unless the patient has
a bilirubin elevation greater than ULN to 1. 5 x ULN resulting from Gilbert's
disease or similar syndrome due to slow conjugation of bilirubin; and
- Alkaline phosphatase less than or equal to 2. 5 x ULN; and
- AST less than or equal to 1. 5 x ULN for the lab.
- If skeletal pain present or alkaline phosphatase greater than ULN (but less than or
equal to 2. 5 x ULN), bone scan or PET scan must not demonstrate metastatic disease
- If AST or alkaline phosphatase greater than ULN , liver imaging (CT, MRI or PET scan)
must not demonstrate definitive metastatic disease and the requirements in criterion
for hepatic function must be met
- Able to swallow oral medications
Exclusion criteria:
- FNA alone to diagnose the primary tumor
- Excisional biopsy or lumpectomy was performed prior to randomization
- Surgical axillary staging procedure prior to randomization. Exceptions: 1) FNA or
core biopsy of an axillary node for any patient, and 2) although not recommended, a
pre-neoadjuvant therapy SN biopsy for patients with clinically negative axillary
nodes.
- Tumors clinically staged as T4
- Ipsilateral cN2b or cN3 disease (Patients with cN1 or cN2a disease are eligible)
- Definitive clinical or radiologic evidence of metastatic disease
- Synchronous bilateral invasive breast cancer
- Requirement for chronic use of any of the medications or substances specified in the
protocol
- Treatment including RT, chemotherapy, and/or targeted therapy for the currently
diagnosed breast cancer prior to randomization
- Any sex hormonal therapy, e. g., birth control pills, ovarian hormone replacement
therapy, etc. (These patients are eligible if therapy is discontinued prior to
randomization)
- Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other
SERM. (Patients are eligible only if these medications are discontinued prior to
randomization)
- Prior history of breast cancer, including DCIS (Patients with a history of LCIS are
eligible)
- Prior therapy with anthracyclines, taxanes, trastuzumab, or lapatinib for any
malignancy
- Other malignancies unless the patient is considered to be disease-free for 5 or more
years prior to randomization and is deemed by her physician to be at low risk for
recurrence. Patients with the following cancers are eligible if diagnosed and
treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ
of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the
skin.
- Cardiac disease that would preclude the use of the drugs included in the B-41
treatment regimens. This includes but is not confined to:
- Active cardiac disease:
- angina pectoris requiring the use of anti-anginal medication;
- ventricular arrhythmias except for benign premature ventricular
contractions controlled by medication;
- conduction abnormality requiring a pacemaker;
- supraventricular and nodal arrhythmias requiring a pacemaker or not
controlled with medication; and
- clinically significant valvular disease.
- History of cardiac disease:
- myocardial infarction;
- congestive heart failure; or
- cardiomyopathy.
- Uncontrolled hypertension, defined as blood pressure greater than 150/90 mm/Hg on
antihypertensive therapy
- History of or current symptomatic interstitial pneumonitis or pulmonary fibrosis or
definitive evidence of interstitial pneumonitis or pulmonary fibrosis described on CT
or chest x-ray in asymptomatic patients
- Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's
CTCAE v3. 0
- Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel,
or other disease significantly affecting gastrointestinal function
- Other non-malignant systemic disease that would preclude treatment with any of the
treatment regimens or would prevent required follow-up
- Conditions that would prohibit administration of corticosteroids
- Administration of any investigational agents within 30 days before randomization
- Pregnancy or lactation
MBCCOP, San Juan, Puerto Rico, San Juan 00936, Puerto Rico
MBCCOP, Gulf Coast, Mobile, Alabama 36608, United States
Scripps Cancer Center-San Diego, La Jolla, California 92037, United States
Pacific Shores Medical Group, Long Beach, California 90813, United States
University of California, Irvine Medical Center, Long Beach, California 90801, United States
St. Joseph Hospital, Orange, California 92868, United States
Desert Regional Medical Center Comprehensive Cancer Center, Palm Springs, California 92262, United States
Stanford University Medical Center, Palo Alto, California 94304, United States
Sutter Medical Center, Sacramento, California 95816, United States
Kaiser Permanente-San Diego, San Diego, California 92120, United States
Santa Rosa Memorial Hospital, Santa Rosa, California 95403, United States
Kaiser Permanente-Vallejo, Vallejo, California 94589, United States
University of Colorado Cancer Center, Aurora, Colorado 80045, United States
Memorial Hospital, Colorado Springs, Colorado 80909, United States
CCOP-Colorado Cancer Research Prog. Inc.(Administrative Only), Denver, Colorado 80224, United States
Kaiser Permanente-Franklin, Denver, Colorado 80205, United States
Kaiser Permanente Rock Creek, Lafayette, Colorado 80026, United States
Hartford Hospital, Hartford, Connecticut 06102, United States
Eastern Connecticut Hematology & Oncology Associates, Norwich, Connecticut 06360, United States
Sibley Memorial Hospital, Washington, District of Columbia 20016, United States
MD Anderson Cancer Center, Orlando, Florida 32806, United States
Phoebe Putney Memorial Hospital, Albany, Georgia 31701, United States
MBCCOP, Medical College of Georgia Research Institute, Augusta, Georgia 30912, United States
Kaiser Permanente Hawaii - Moanalua Med Center, Honolulu, Hawaii 96819, United States
University of Hawaii, Honolulu, Hawaii 96813, United States
Kootenai Cancer Center, Coeur D'Alene, Idaho 83814, United States
Rush University Medical Center, Chicago, Illinois 60612, United States
Decatur Memorial Hospital, Decatur, Illinois 62526, United States
Cancer Institute at Alexian Brothers Hospital Network, Elk Grove, Illinois 60007, United States
Edward Hospital, Naperville, Illinois 60566, United States
Edward Cancer Center Plainfield, Plainfield, Illinois 60585, United States
CCOP, Central Illinois, Springfield, Illinois 62526, United States
CCOP, Carle Cancer Center, Urbana, Illinois 61801, United States
St. Vincent Hospital and Health Care Center, Indianapolis, Indiana 46260, United States
CCOP, Northern Indiana Cancer Research Consortium, South Bend, Indiana 46601, United States
CCOP, Des Moines, IA, Des Moines, Iowa 52501, United States
University of Iowa, Iowa City, Iowa 52242, United States
CCOP, Sioux Community Cancer consortium, Sioux City, Iowa 51101, United States
CCOP, Wichita KS, Wichita, Kansas 67214, United States
University of Kentucky Medical Center, Lexington, Kentucky 40536, United States
NortonHealtcare Inc., Louisville, Kentucky 40202, United States
CCOP, Ochsner Clinic Foundation, New Orleans, Louisiana 70121, United States
Franklin Square Hospital Center, Baltimore, Maryland 21237, United States
Greater Baltimore Medical Center, Baltimore, Maryland 21204, United States
Boston Medical Center, Boston, Massachusetts 02118, United States
CCOP, Michigan Cancer Research Consortium, Ann Arbor, Michigan 48106, United States
Henry Ford Health System, Detroit, Michigan 48202, United States
Henry Ford Hospital, Detroit, Michigan 48202, United States
CCOP, Grand Rapids Clnical Oncology Program, Grand Rapids, Michigan 49503, United States
CCOP, Kalamazoo, MI, Kalamazoo, Michigan 49007, United States
Michigan State University - Breslin Cancer Center, Lansing, Michigan 48910, United States
CCOP, William Beaumont Hospital, Royal Oak, Michigan 48073, United States
Providence Hospital - Southfield, Southfield, Michigan 48075-9975, United States
CCOP, Metro-Minnesota, Minneapolis, Minnesota 55416, United States
Hennepin County Medical Center, Minneapolis, Minnesota 55415, United States
University of Missouri-Ellis Fischel, Columbia, Missouri 65203, United States
CCOP, Kansas City (Administrative Only), Kansas City, Missouri 64131, United States
CCOP, Ozark Health Ventures LLC, Springfield, Missouri 65804, United States
CCOP, Heartland Cancer Research, St. Louis, Missouri 63131, United States
Saint Louis UniversityHealth Sciences Center, St. Louis, Missouri 63110, United States
CCOP, Montana Cancer Consortium, Billings, Montana 59101, United States
CCOP, Missouri Valley Consortium, Omaha, Nebraska 74136, United States
Cancer Institute of New Jersey, New Brunswick, New Jersey 08901, United States
Newark Beth Israel Medical Center, Newark, New Jersey 07112, United States
New York Oncology Hematology PC-Albany, Albany, New York 12206, United States
Cancer Center at Glens Falls Hospital, Glens Falls, New York 12801, United States
CCOP, Hematology-Oncology Associates of CNY, Syracuse, New York 13057, United States
Alamance Regional Medical Center, Burlington, North Carolina 27215, United States
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 28302, United States
CCOP, Southeast Cancer Control Consortium, Charlotte, North Carolina 28203, United States
Alamance Regional Medical Center - Off site Clinic, Mebane, North Carolina 27302, United States
Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, United States
Akron City Hospital, Akron, Ohio 44304, United States
Aultman Hospital, Canton, Ohio 44710, United States
Case Western Reserve/University Hospitals-Ireland Cancer Cntr., Cleveland, Ohio 44106, United States
CCOP, Columbus, OH, Columbus, Ohio 43215, United States
Ohio State University, Columbus, Ohio 43017, United States
CCOP, Dayton, OH, Dayton, Ohio 45429, United States
CCOP, Oklahoma, Tulsa, Oklahoma 74136, United States
Odette Cancer Centre, Toronto, Ontario M4N 3M5, Canada
Lehigh Valley Hospital, Allentown, Pennsylvania 18105, United States
Geisinger Clinic, Danville, Pennsylvania 17882-2170, United States
Hershey Medical Center, Hershey, Pennsylvania 17033, United States
Albert Einstein Healthcare Network, Philadelphia, Pennsylvania 19141-3098, United States
Allegheny General Hospital/Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania 15212, United States
NSABP Foundation, Inc., Pittsburgh, Pennsylvania 15212, United States
University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Western Pennsylvania Hospital, Pittsburgh, Pennsylvania 15224, United States
Mercy Hospital, Scranton, Pennsylvania 18501, United States
Reading Hospital & Medical Center, West Reading, Pennsylvania 19612, United States
CCOP, Main Line Health, Wynnewood, Pennsylvania 19096, United States
Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada
Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada
St. Mary's Hospital Center, Montreal, Quebec H3T 1M5, Canada
University of Montreal Hospital Group, Montreal, Quebec, Canada
Centre Hospitalier Affilie Universitaire De Quebec, Hospital du St-Sacrement, Quebec City, Quebec G1S 4L8, Canada
CCOP, Upstate Carolina, Spartanburg, South Carolina 29303, United States
Sanford Cancer Center, Souix Falls, South Dakota 57104, United States
Thompson Cancer Survival Center-Dowell Springs, Knoxville, Tennessee 37909, United States
Joe Arrington Cancer Research & Treatment Center, Lubbock, Texas 79410, United States
University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, United States
MBCCOP, Virginia Commonwealth University, Richmond, Virginia 23298, United States
CCOP, Virginia Mason, Seattle, Washington 99519, United States
Puget Sound Oncology Consortium, Seattle, Washington 98109, United States
CCOP, Northwest, Tacoma, Washington 83706, United States
West Virginia University Hospitals Inc., Morgantown, West Virginia 26506-9162, United States
Camden-Clark Memorial Hospital, Parkersburg, West Virginia 26101, United States
Wheeling Hospital, Wheeling, West Virginia 26003, United States
CCOP, Marshfield Clinic, Marshfield, Wisconsin 54449, United States
Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States
Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. doi: 10.1016/S1470-2045(13)70411-X. Epub 2013 Oct 4.