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

NCT00486668 | Unknown Phase 3 DMC

• 1 other identifier: NSABP B-41
• Study Type: interventional
• Target: 529
• Locations: 3 countries
• Sites: 110

Brief Summary

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.

Conditions

Invasive Breast Cancer

Keywords

HER2 positive breast cancer; invasive breast cancer; lapatinib; neoadjuvant; NSABP; paclitaxel; trastuzumab; doxorubicin; cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Determination of pathologic complete response (pCR), defined by the absence of microscopic evidence of invasive tumor cells in the post chemotherapy surgical breast specimen.

  surgery following chemotherapy

Secondary Outcomes (7)

• The determination of pCR in the surgical breast and lymph node specimens following chemotherapy.

  surgery following chemotherapy

• Clinical tumor measurement as assessed by physical exam of the breast and lymph nodes

  baseline (prior to starting protocol therapy), at the completion of AC (before starting paclitaxel and trastuzumab and/or lapatinib), and at the conclusion of the sequential regimens (prior to surgery).

• Determination of cardiac toxicity as measured by the incidence of cardiac events defined as definite or probable cardiac death

  two year cumulative incidence

• Determination of non-cardiac toxicities as measured by frequencies of adverse events categorized using CTCAE v3.0.

  through 5 years after entry

• Overall survival as measured by time from randomization until death from any cause.

  through 5 years after entry

Study Arms (3)

Group 1: AC then paclitaxel + trastuzumab

ACTIVE COMPARATOR

AC followed by paclitaxel plus trastuzumab

Drug: doxorubicin; Drug: cyclophosphamide; Drug: paclitaxel; Drug: trastuzumab

Group 2: AC then paclitaxel + lapatinib

EXPERIMENTAL

AC followed by paclitaxel plus lapatinib

Drug: doxorubicin; Drug: cyclophosphamide; Drug: paclitaxel; Drug: lapatinib

Group 3: AC then paclitaxel + trastuzumab + lapatinib

EXPERIMENTAL

AC followed by paclitaxel plus trastuzumab plus lapatinib

Drug: doxorubicin; Drug: cyclophosphamide; Drug: paclitaxel; Drug: trastuzumab; Drug: lapatinib

Interventions

doxorubicin DRUG

60 mg/m2 IV every 21 days for cycles 1-4

Group 1: AC then paclitaxel + trastuzumab; Group 2: AC then paclitaxel + lapatinib; Group 3: AC then paclitaxel + trastuzumab + lapatinib

cyclophosphamide DRUG

600 mg/m2 IV every 21 days for cycles 1-4

Group 1: AC then paclitaxel + trastuzumab; Group 2: AC then paclitaxel + lapatinib; Group 3: AC then paclitaxel + trastuzumab + lapatinib

paclitaxel DRUG

80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8

Group 1: AC then paclitaxel + trastuzumab; Group 2: AC then paclitaxel + lapatinib; Group 3: AC then paclitaxel + trastuzumab + lapatinib

trastuzumab DRUG

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 1: AC then paclitaxel + trastuzumab; Group 3: AC then paclitaxel + trastuzumab + lapatinib

lapatinib DRUG

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 2: AC then paclitaxel + lapatinib; Group 3: AC then paclitaxel + trastuzumab + lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female
• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• GlaxoSmithKline: collaborator

Study Sites (110)

MBCCOP, Gulf Coast

Mobile, Alabama, 36608, United States

Location

Scripps Cancer Center-San Diego

La Jolla, California, 92037, United States

Location

University of California, Irvine Medical Center

Long Beach, California, 90801, United States

Location

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

St. Joseph Hospital

Orange, California, 92868, United States

Location

Desert Regional Medical Center Comprehensive Cancer Center

Palm Springs, California, 92262, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Sutter Medical Center

Sacramento, California, 95816, United States

Location

Kaiser Permanente-San Diego

San Diego, California, 92120, United States

Location

Santa Rosa Memorial Hospital

Santa Rosa, California, 95403, United States

Location

Kaiser Permanente-Vallejo

Vallejo, California, 94589, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Memorial Hospital

Colorado Springs, Colorado, 80909, United States

Location

Kaiser Permanente-Franklin

Denver, Colorado, 80205, United States

Location

CCOP-Colorado Cancer Research Prog. Inc.(Administrative Only)

Denver, Colorado, 80224, United States

Location

Kaiser Permanente Rock Creek

Lafayette, Colorado, 80026, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Eastern Connecticut Hematology & Oncology Associates

Norwich, Connecticut, 06360, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

MD Anderson Cancer Center

Orlando, Florida, 32806, United States

Location

Phoebe Putney Memorial Hospital

Albany, Georgia, 31701, United States

Location

MBCCOP, Medical College of Georgia Research Institute

Augusta, Georgia, 30912, United States

Location

University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Kaiser Permanente Hawaii - Moanalua Med Center

Honolulu, Hawaii, 96819, United States

Location

Kootenai Cancer Center

Coeur d'Alene, Idaho, 83814, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Cancer Institute at Alexian Brothers Hospital Network

Elk Grove, Illinois, 60007, United States

Location

Edward Hospital

Naperville, Illinois, 60566, United States

Location

Edward Cancer Center Plainfield

Plainfield, Illinois, 60585, United States

Location

CCOP, Central Illinois

Springfield, Illinois, 62526, United States

Location

CCOP, Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

St. Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

CCOP, Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46601, United States

Location

CCOP, Des Moines, IA

Des Moines, Iowa, 52501, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

CCOP, Sioux Community Cancer consortium

Sioux City, Iowa, 51101, United States

Location

CCOP, Wichita KS

Wichita, Kansas, 67214, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

NortonHealtcare Inc.

Louisville, Kentucky, 40202, United States

Location

CCOP, Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Franklin Square Hospital Center

Baltimore, Maryland, 21237, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

CCOP, Michigan Cancer Research Consortium

Ann Arbor, Michigan, 48106, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

CCOP, Grand Rapids Clnical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

CCOP, Kalamazoo, MI

Kalamazoo, Michigan, 49007, United States

Location

Michigan State University - Breslin Cancer Center

Lansing, Michigan, 48910, United States

Location

CCOP, William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

Providence Hospital - Southfield

Southfield, Michigan, 48075-9975, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

CCOP, Metro-Minnesota

Minneapolis, Minnesota, 55416, United States

Location

University of Missouri-Ellis Fischel

Columbia, Missouri, 65203, United States

Location

CCOP, Kansas City (Administrative Only)

Kansas City, Missouri, 64131, United States

Location

CCOP, Ozark Health Ventures LLC

Springfield, Missouri, 65804, United States

Location

Saint Louis UniversityHealth Sciences Center

St Louis, Missouri, 63110, United States

Location

CCOP, Heartland Cancer Research

St Louis, Missouri, 63131, United States

Location

CCOP, Montana Cancer Consortium

Billings, Montana, 59101, United States

Location

CCOP, Missouri Valley Consortium

Omaha, Nebraska, 74136, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

New York Oncology Hematology PC-Albany

Albany, New York, 12206, United States

Location

Cancer Center at Glens Falls Hospital

Glens Falls, New York, 12801, United States

Location

CCOP, Hematology-Oncology Associates of CNY

Syracuse, New York, 13057, United States

Location

Alamance Regional Medical Center

Burlington, North Carolina, 27215, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 28302, United States

Location

CCOP, Southeast Cancer Control Consortium

Charlotte, North Carolina, 28203, United States

Location

Alamance Regional Medical Center - Off site Clinic

Mebane, North Carolina, 27302, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Akron City Hospital

Akron, Ohio, 44304, United States

Location

Aultman Hospital

Canton, Ohio, 44710, United States

Location

Case Western Reserve/University Hospitals-Ireland Cancer Cntr.

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43017, United States

Location

CCOP, Columbus, OH

Columbus, Ohio, 43215, United States

Location

CCOP, Dayton, OH

Dayton, Ohio, 45429, United States

Location

CCOP, Oklahoma

Tulsa, Oklahoma, 74136, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18105, United States

Location

Geisinger Clinic

Danville, Pennsylvania, 17882-2170, United States

Location

Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Albert Einstein Healthcare Network

Philadelphia, Pennsylvania, 19141-3098, United States

Location

Allegheny General Hospital/Allegheny-Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

NSABP Foundation, Inc.

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Mercy Hospital

Scranton, Pennsylvania, 18501, United States

Location

Reading Hospital & Medical Center

West Reading, Pennsylvania, 19612, United States

Location

CCOP, Main Line Health

Wynnewood, Pennsylvania, 19096, United States

Location

CCOP, Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

Sanford Cancer Center

Souix Falls, South Dakota, 57104, United States

Location

Thompson Cancer Survival Center-Dowell Springs

Knoxville, Tennessee, 37909, United States

Location

Joe Arrington Cancer Research & Treatment Center

Lubbock, Texas, 79410, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MBCCOP, Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Puget Sound Oncology Consortium

Seattle, Washington, 98109, United States

Location

CCOP, Virginia Mason

Seattle, Washington, 99519, United States

Location

CCOP, Northwest

Tacoma, Washington, 83706, United States

Location

West Virginia University Hospitals Inc.

Morgantown, West Virginia, 26506-9162, United States

Location

Camden-Clark Memorial Hospital

Parkersburg, West Virginia, 26101, United States

Location

Wheeling Hospital

Wheeling, West Virginia, 26003, United States

Location

CCOP, Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

St. Mary's Hospital Center

Montreal, Quebec, H3T 1M5, Canada

Location

University of Montreal Hospital Group

Montreal, Quebec, Canada

Location

Centre Hospitalier Affilie Universitaire De Quebec, Hospital du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

MBCCOP, San Juan, Puerto Rico

San Juan, 00936, Puerto Rico

Location

Related Publications (2)

• 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.

  PMID: 24095300 BACKGROUND

• 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.

  PMID: 36944848 DERIVED

MeSH Terms

Interventions

Doxorubicin; Cyclophosphamide; Paclitaxel; Trastuzumab; Lapatinib

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2007
• First Posted: June 15, 2007
• Study Start: July 1, 2007
• Primary Completion: June 1, 2012
• Study Completion: March 1, 2017
• Last Updated: June 6, 2016

Record last verified: 2016-06

Locations

CA (6); US (103); PR (1)