A Study of AC Followed by a Combination of Paclitaxel Plus Trastuzumab or Lapatinib or Both Given Before Surgery to Patients With Operable HER2 Positive Invasive Breast Cancer
NCT ID: NCT00486668
Last Updated: 2016-06-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
529 participants
INTERVENTIONAL
2007-07-31
2017-03-31
Brief Summary
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Detailed Description
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Availability of a second agent that can interrupt HER2-signaling pathways through completely different mechanisms than those of trastuzumab offers the potential for further improvement in the management of patients with HER2-overexpressing breast cancer in both the adjuvant and metastatic setting. Co-administration of both trastuzumab and lapatinib with chemotherapy may be important in improving outcomes in subsets of HER2-positive breast cancers. However, use of two inhibitors of the HER2 pathway will increase costs and may increase toxicity, so it will be important to identify the subsets of patients who would benefit from the dual therapy. Inhibition of HER2 with a single agent clearly is sufficient for many patients as evidenced by the results of the trastuzumab trials. Therefore, co-administration to unselected populations of women with HER2-positive breast cancers would not represent an optimal approach. Given the activity of lapatinib, it is likely that it will also be sufficiently active in inhibiting HER2-pathway activation in some patients to allow for its use as the sole inhibitor of the HER2 pathway. Different populations may also derive greater benefit from one of the HER2-blocking agents relative to the other. Identification of potential predictive factors for pathologic complete response to the combination or to either agent administered alone in neoadjuvant trials would provide important information for adjuvant trials designed to definitively address these important issues.
This study will compare 3 combined chemotherapy regimens: AC followed by paclitaxel plus trastuzumab and lapatinib, AC followed by paclitaxel plus lapatinib, and AC followed by paclitaxel plus trastuzumab given before surgery to patients with HER2-positive breast cancer.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Group 1: AC then paclitaxel + trastuzumab
AC followed by paclitaxel plus trastuzumab
doxorubicin
60 mg/m2 IV every 21 days for cycles 1-4
cyclophosphamide
600 mg/m2 IV every 21 days for cycles 1-4
paclitaxel
80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8
trastuzumab
First dose: 4 mg/kg IV, subsequent doses: 2 mg/kg IV weekly beginning on day 1 of the first paclitaxel cycle until 1-7 days before surgery
Group 2: AC then paclitaxel + lapatinib
AC followed by paclitaxel plus lapatinib
doxorubicin
60 mg/m2 IV every 21 days for cycles 1-4
cyclophosphamide
600 mg/m2 IV every 21 days for cycles 1-4
paclitaxel
80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8
lapatinib
Group 2: 1250 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery. Group 3: 750 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery.
Group 3: AC then paclitaxel + trastuzumab + lapatinib
AC followed by paclitaxel plus trastuzumab plus lapatinib
doxorubicin
60 mg/m2 IV every 21 days for cycles 1-4
cyclophosphamide
600 mg/m2 IV every 21 days for cycles 1-4
paclitaxel
80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8
trastuzumab
First dose: 4 mg/kg IV, subsequent doses: 2 mg/kg IV weekly beginning on day 1 of the first paclitaxel cycle until 1-7 days before surgery
lapatinib
Group 2: 1250 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery. Group 3: 750 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery.
Interventions
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doxorubicin
60 mg/m2 IV every 21 days for cycles 1-4
cyclophosphamide
600 mg/m2 IV every 21 days for cycles 1-4
paclitaxel
80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8
trastuzumab
First dose: 4 mg/kg IV, subsequent doses: 2 mg/kg IV weekly beginning on day 1 of the first paclitaxel cycle until 1-7 days before surgery
lapatinib
Group 2: 1250 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery. Group 3: 750 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery.
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
FEMALE
No
Sponsors
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GlaxoSmithKline
INDUSTRY
NSABP Foundation Inc
NETWORK
Responsible Party
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Principal Investigators
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Norman Wolmark, MD
Role: PRINCIPAL_INVESTIGATOR
NSABP Foundation Inc
Locations
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MBCCOP, Gulf Coast
Mobile, Alabama, United States
Scripps Cancer Center-San Diego
La Jolla, California, United States
University of California, Irvine Medical Center
Long Beach, California, United States
Pacific Shores Medical Group
Long Beach, California, United States
St. Joseph Hospital
Orange, California, United States
Desert Regional Medical Center Comprehensive Cancer Center
Palm Springs, California, United States
Stanford University Medical Center
Palo Alto, California, United States
Sutter Medical Center
Sacramento, California, United States
Kaiser Permanente-San Diego
San Diego, California, United States
Santa Rosa Memorial Hospital
Santa Rosa, California, United States
Kaiser Permanente-Vallejo
Vallejo, California, United States
University of Colorado Cancer Center
Aurora, Colorado, United States
Memorial Hospital
Colorado Springs, Colorado, United States
Kaiser Permanente-Franklin
Denver, Colorado, United States
CCOP-Colorado Cancer Research Prog. Inc.(Administrative Only)
Denver, Colorado, United States
Kaiser Permanente Rock Creek
Lafayette, Colorado, United States
Hartford Hospital
Hartford, Connecticut, United States
Eastern Connecticut Hematology & Oncology Associates
Norwich, Connecticut, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, United States
MD Anderson Cancer Center
Orlando, Florida, United States
Phoebe Putney Memorial Hospital
Albany, Georgia, United States
MBCCOP, Medical College of Georgia Research Institute
Augusta, Georgia, United States
University of Hawaii
Honolulu, Hawaii, United States
Kaiser Permanente Hawaii - Moanalua Med Center
Honolulu, Hawaii, United States
Kootenai Cancer Center
Coeur d'Alene, Idaho, United States
Rush University Medical Center
Chicago, Illinois, United States
Decatur Memorial Hospital
Decatur, Illinois, United States
Cancer Institute at Alexian Brothers Hospital Network
Elk Grove, Illinois, United States
Edward Hospital
Naperville, Illinois, United States
Edward Cancer Center Plainfield
Plainfield, Illinois, United States
CCOP, Central Illinois
Springfield, Illinois, United States
CCOP, Carle Cancer Center
Urbana, Illinois, United States
St. Vincent Hospital and Health Care Center
Indianapolis, Indiana, United States
CCOP, Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States
CCOP, Des Moines, IA
Des Moines, Iowa, United States
University of Iowa
Iowa City, Iowa, United States
CCOP, Sioux Community Cancer consortium
Sioux City, Iowa, United States
CCOP, Wichita KS
Wichita, Kansas, United States
University of Kentucky Medical Center
Lexington, Kentucky, United States
NortonHealtcare Inc.
Louisville, Kentucky, United States
CCOP, Ochsner Clinic Foundation
New Orleans, Louisiana, United States
Greater Baltimore Medical Center
Baltimore, Maryland, United States
Franklin Square Hospital Center
Baltimore, Maryland, United States
Boston Medical Center
Boston, Massachusetts, United States
CCOP, Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
CCOP, Grand Rapids Clnical Oncology Program
Grand Rapids, Michigan, United States
CCOP, Kalamazoo, MI
Kalamazoo, Michigan, United States
Michigan State University - Breslin Cancer Center
Lansing, Michigan, United States
CCOP, William Beaumont Hospital
Royal Oak, Michigan, United States
Providence Hospital - Southfield
Southfield, Michigan, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
CCOP, Metro-Minnesota
Minneapolis, Minnesota, United States
University of Missouri-Ellis Fischel
Columbia, Missouri, United States
CCOP, Kansas City (Administrative Only)
Kansas City, Missouri, United States
CCOP, Ozark Health Ventures LLC
Springfield, Missouri, United States
Saint Louis UniversityHealth Sciences Center
St Louis, Missouri, United States
CCOP, Heartland Cancer Research
St Louis, Missouri, United States
CCOP, Montana Cancer Consortium
Billings, Montana, United States
CCOP, Missouri Valley Consortium
Omaha, Nebraska, United States
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
New York Oncology Hematology PC-Albany
Albany, New York, United States
Cancer Center at Glens Falls Hospital
Glens Falls, New York, United States
CCOP, Hematology-Oncology Associates of CNY
Syracuse, New York, United States
Alamance Regional Medical Center
Burlington, North Carolina, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
CCOP, Southeast Cancer Control Consortium
Charlotte, North Carolina, United States
Alamance Regional Medical Center - Off site Clinic
Mebane, North Carolina, United States
Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States
Akron City Hospital
Akron, Ohio, United States
Aultman Hospital
Canton, Ohio, United States
Case Western Reserve/University Hospitals-Ireland Cancer Cntr.
Cleveland, Ohio, United States
Ohio State University
Columbus, Ohio, United States
CCOP, Columbus, OH
Columbus, Ohio, United States
CCOP, Dayton, OH
Dayton, Ohio, United States
CCOP, Oklahoma
Tulsa, Oklahoma, United States
Lehigh Valley Hospital
Allentown, Pennsylvania, United States
Geisinger Clinic
Danville, Pennsylvania, United States
Hershey Medical Center
Hershey, Pennsylvania, United States
Albert Einstein Healthcare Network
Philadelphia, Pennsylvania, United States
Allegheny General Hospital/Allegheny-Singer Research Institute
Pittsburgh, Pennsylvania, United States
NSABP Foundation, Inc.
Pittsburgh, Pennsylvania, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States
Mercy Hospital
Scranton, Pennsylvania, United States
Reading Hospital & Medical Center
West Reading, Pennsylvania, United States
CCOP, Main Line Health
Wynnewood, Pennsylvania, United States
CCOP, Upstate Carolina
Spartanburg, South Carolina, United States
Sanford Cancer Center
Souix Falls, South Dakota, United States
Thompson Cancer Survival Center-Dowell Springs
Knoxville, Tennessee, United States
Joe Arrington Cancer Research & Treatment Center
Lubbock, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
MBCCOP, Virginia Commonwealth University
Richmond, Virginia, United States
Puget Sound Oncology Consortium
Seattle, Washington, United States
CCOP, Virginia Mason
Seattle, Washington, United States
CCOP, Northwest
Tacoma, Washington, United States
West Virginia University Hospitals Inc.
Morgantown, West Virginia, United States
Camden-Clark Memorial Hospital
Parkersburg, West Virginia, United States
Wheeling Hospital
Wheeling, West Virginia, United States
CCOP, Marshfield Clinic
Marshfield, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Odette Cancer Centre
Toronto, Ontario, Canada
Royal Victoria Hospital
Montreal, Quebec, Canada
Jewish General Hospital
Montreal, Quebec, Canada
St. Mary's Hospital Center
Montreal, Quebec, Canada
University of Montreal Hospital Group
Montreal, Quebec, Canada
Centre Hospitalier Affilie Universitaire De Quebec, Hospital du St-Sacrement
Québec, Quebec, Canada
MBCCOP, San Juan, Puerto Rico
San Juan, , Puerto Rico
Countries
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References
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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.
Rastogi P, Tang G, Hassan S, Geyer CE Jr, Azar CA, Magrinat GC, Suga JM, Bear HD, Baez-Diaz L, Sarwar S, Boileau JF, Brufsky AM, Shibata HR, Bandos H, Paik S, Yothers G, Swain SM, Mamounas EP, Wolmark N. Long-term outcomes of dual vs single HER2-directed neoadjuvant therapy in NSABP B-41. Breast Cancer Res Treat. 2023 Jun;199(2):243-252. doi: 10.1007/s10549-023-06881-8. Epub 2023 Mar 22.
Other Identifiers
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NSABP B-41
Identifier Type: -
Identifier Source: org_study_id
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