Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery

Randomized Phase III Trial of Paclitaxel +Trastuzumab + Lapatinib Versus Paclitaxel + Trastuzumab as Neoadjuvant Treatment of HER2-Positive Primary Breast Cancer

This randomized phase III trial studies paclitaxel and trastuzumab with or without lapatinib to see how well they work in treating patients with stage II or stage III breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel with trastuzumab and/or lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which regimen is more effective in treating patients with breast cancer.

Study Overview

• Status: Completed
• Conditions: Male Breast Carcinoma; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Trastuzumab; Drug: Paclitaxel; Drug: Lapatinib Ditosylate

Detailed Description

PRIMARY OBJECTIVE:

I. To determine if the pathologic complete response (pCR) in the breast to neoadjuvant weekly paclitaxel with trastuzumab plus lapatinib (THL) is 20% greater than the pCR to weekly paclitaxel with trastuzumab alone (TH).

SECONDARY OBJECTIVES:

I. To determine the pathologic complete response in the breast and axilla, using American Joint Committee on Cancer (AJCC) Tumor, Lymph Nodes and Metastasis (TMN) criteria (version 6), to neoadjuvant weekly paclitaxel plus human epidermal growth factor 2 (HER2)- targeted therapy in patients with HER2-positive operable breast cancer.

II. To evaluate residual cancer burden (RCB) as a predictor of long term relapse free survival (RFS) and overall survival (OS).

III. To document the toxicity of all chemotherapeutic regimens (THL, TH). IV. To determine the correlation between clinical, radiographic and pathologic response.

V. To compare overall survival (OS), relapse free survival (RFS) and time to first failure (TFF) among the treatment groups.

VI. To obtain blood, fresh frozen and fixed tumor tissue to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in blood, serum and tissue that are likely to influence response to and toxicity of trastuzumab alone or trastuzumab plus lapatinib, when given with paclitaxel.

VII. To determine the surgical practice patterns for breast conservation and sentinel lymphadenectomy in patients undergoing neoadjuvant chemotherapy.

VIII. To determine the radiotherapy practice patterns for post-mastectomy and regional nodal irradiation in patients undergoing neoadjuvant chemotherapy.

IX. To evaluate pharmacogenomic determinants of toxicity.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive trastuzumab IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and lapatinib ditosylate orally (PO) once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive trastuzumab and paclitaxel as in arm I.

ARM III: Patients receive paclitaxel and lapatinib ditosylate as in arm I. (Discontinued as of 6-15-11) Within 42 days after completion of neoadjuvant therapy, patients in both arms undergo definitive surgery (breast conservation or total mastectomy).

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 10 years.

• Study Type: Interventional
• Enrollment (Actual): 305
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • San Juan City Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
  • Arkansas
    • Fort Smith, Arkansas, United States, 72901
      • Sparks Regional Medical Center
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Castro Valley, California, United States, 94546
      • Valley Medical Oncology Consultants-Castro Valley
    • Emeryville, California, United States, 94608
      • Bay Area Breast Surgeons Inc
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Camino Division
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Hematology and Oncology Associates-Oakland
    • Oakland, California, United States, 94609
      • Tom K Lee Inc
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • Oakland, California, United States, 94602
      • Wilma Chan Highland Hospital
    • Palm Springs, California, United States, 92262
      • Desert Regional Medical Center
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Health Care
    • Pleasanton, California, United States, 94588
      • Valley Care Health System - Pleasanton
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Saint Helena, California, United States, 94574
      • Saint Helena Hospital
    • Salinas, California, United States, 93901
      • Salinas Valley Memorial
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80303
      • Boulder Community Foothills Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80222
      • Western States Cancer Research NCORP
    • Denver, Colorado, United States, 80218
      • Saint Joseph Hospital - Cancer Centers of Colorado
    • Denver, Colorado, United States, 80210
      • AdventHealth Porter
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Grand Junction, Colorado, United States, 81501
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • Banner North Colorado Medical Center
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Littleton, Colorado, United States, 80122
      • AdventHealth Littleton
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • Banner McKee Medical Center
    • Parker, Colorado, United States, 80138
      • AdventHealth Parker
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
    • Wheat Ridge, Colorado, United States, 80401
      • Intermountain Health Lutheran Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • Manchester, Connecticut, United States, 06040
      • Manchester Memorial Hospital
    • Middletown, Connecticut, United States, 06457
      • Middlesex Hospital
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Halifax Health Medical Center-Centers for Oncology
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Gainesville, Florida, United States, 32605
      • Florida Cancer Specialists-Gainesville Cancer Center
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Weston, Florida, United States, 33331
      • Cleveland Clinic-Weston
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Atlanta, Georgia, United States, 30342
      • Atlanta Regional CCOP
    • Austell, Georgia, United States, 30106
      • WellStar Cobb Hospital
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Decatur, Georgia, United States, 30033
      • Emory Decatur Hospital
    • Fayetteville, Georgia, United States, 30214
      • Piedmont Fayette Hospital
    • Lawrenceville, Georgia, United States, 30046
      • Northside Hospital - Gwinnett
    • Macon, Georgia, United States, 31201
      • Atrium Health Navicent
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital
    • Riverdale, Georgia, United States, 30274
      • Southern Regional Medical Center
    • Rome, Georgia, United States, 30165
      • Harbin Clinic Medical Oncology and Clinical Research
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Alton, Illinois, United States, 62002
      • OSF Saint Anthony's Health Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60608
      • Mount Sinai Hospital Medical Center
    • Chicago, Illinois, United States, 60631
      • Presence Resurrection Medical Center
    • Chicago, Illinois, United States, 60640
      • Weiss Memorial Hospital
    • Downers Grove, Illinois, United States, 60515
      • Advocate Good Samaritan Hospital
    • Joliet, Illinois, United States, 60435
      • Duly Health and Care Joliet
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • SSM Health Good Samaritan
    • Oak Lawn, Illinois, United States, 60453-2699
      • Advocate Christ Medical Center
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Franciscan Saint Francis Health-Beech Grove
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Bettendorf, Iowa, United States, 52722
      • University of Iowa Healthcare Cancer Services Quad Cities
    • Clive, Iowa, United States, 50325
      • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Des Moines, Iowa, United States, 50309
      • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    • Des Moines, Iowa, United States, 50314
      • UI Health Care Mission Cancer and Blood - Laurel Clinic
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51102
      • Mercy Medical Center-Sioux City
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
  • Kansas
    • Hays, Kansas, United States, 67601
      • HaysMed
    • Hutchinson, Kansas, United States, 67502
      • Hutchinson Regional Medical Center
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Pittsburg, Kansas, United States, 66762
      • Mercy Hospital Pittsburg
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Topeka, Kansas, United States, 66606
      • University of Kansas Health System Saint Francis Campus
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center / Stormont Vail Health
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Bethesda, Maryland, United States, 20889-5600
      • Walter Reed National Military Medical Center
    • Elkton, Maryland, United States, 21921
      • Christiana Care - Union Hospital
    • Salisbury, Maryland, United States, 21801
      • TidalHealth Peninsula Regional
    • Silver Spring, Maryland, United States, 20910
      • Holy Cross Hospital
  • Massachusetts
    • Attleboro, Massachusetts, United States, 02703
      • Sturdy Memorial Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Brighton, Massachusetts, United States, 02135
      • Dana-Farber Cancer Institute at Boston Medical Center - Brighton
    • Milford, Massachusetts, United States, 01757
      • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional
    • Newton, Massachusetts, United States, 02462
      • Newton-Wellesley Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Dearborn, Michigan, United States, 48124
      • Corewell Health Dearborn Hospital
    • Detroit, Michigan, United States, 48236
      • Henry Ford Health Saint John Hospital
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Blanc, Michigan, United States, 48439
      • Genesys Regional Medical Center
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Beacon Kalamazoo
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Pontiac, Michigan, United States, 48341
      • Trinity Health Saint Joseph Mercy Oakland Hospital
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
    • Southfield, Michigan, United States, 48075
      • Henry Ford Health Providence Southfield Hospital
    • Warren, Michigan, United States, 48093
      • Henry Ford Health Warren Hospital
  • Minnesota
    • Mankato, Minnesota, United States, 56001
      • Mayo Clinic Health Systems-Mankato
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Hospital
    • Cape Girardeau, Missouri, United States, 63703
      • Mercy Cancer Center - Cape Girardeau
    • Jefferson City, Missouri, United States, 65109
      • MU Health Care Goldschmidt Cancer Center
    • Kansas City, Missouri, United States, 64108
      • University Health Truman Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
    • Saint Louis, Missouri, United States, 63141
      • Center for Cancer Care and Research
    • Saint Louis, Missouri, United States, 63141
      • Comprehensive Cancer Care PC
    • Saint Louis, Missouri, United States, 63109
      • Mercy Infusion Center - Chippewa
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59102
      • Montana Cancer Consortium NCORP
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59102
      • Saint Vincent Frontier Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Health Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Berdeaux, Donald MD (UIA Investigator)
    • Great Falls, Montana, United States, 59405
      • Benefis Sletten Cancer Institute
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Kalispell, Montana, United States, 59901
      • Logan Health Medical Center
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
    • Missoula, Montana, United States, 59804
      • Community Medical Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Cancer Research Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68106
      • Missouri Valley Cancer Consortium
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89120
      • Nevada Cancer Research Foundation NCORP
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology Hematology PA-Concord
    • Keene, New Hampshire, United States, 03431
      • Cheshire Medical Center-Dartmouth-Hitchcock Keene
    • Laconia, New Hampshire, United States, 03246
      • LRGHealthcare-Lakes Region General Hospital
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • Manchester, New Hampshire, United States, 03103
      • Solinsky Center for Cancer Care
    • Manchester, New Hampshire, United States, 03103
      • Elliot Hospital
    • Manchester, New Hampshire, United States, 03102
      • Dartmouth Cancer Center - Manchester
    • Nashua, New Hampshire, United States, 03060
      • Foundation Medical Partners
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Newark, New Jersey, United States, 07101
      • Rutgers New Jersey Medical School
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Center-Saint Joseph Square
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87106
      • Hematology Oncology Associates
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Elmhurst, New York, United States, 11373
      • Elmhurst Hospital Center
    • Jamaica, New York, United States, 11432
      • Queens Hospital Center
    • Lake Success, New York, United States, 11042
      • Northwell Health NCORP
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • Middletown, New York, United States, 10940
      • Garnet Health Medical Center
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Poughkeepsie, New York, United States, 12601
      • Vassar Brothers Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Burlington, North Carolina, United States, 27215
      • Cone Health Cancer Center at Alamance Regional
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Concord, North Carolina, United States, 28025
      • Atrium Health Cabarrus/LCI-Concord
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Kinston, North Carolina, United States, 28501
      • ECU Health Oncology Kinston
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Raleigh, North Carolina, United States, 27607
      • UNC Rex Healthcare
    • Washington, North Carolina, United States, 27889
      • Marion L Shepard Cancer Center - ECU Health Beaufort Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Bismarck, North Dakota, United States, 58501
      • Saint Alexius Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Beachwood, Ohio, United States, 44122
      • Cleveland Clinic Cancer Center Beachwood
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45459
      • Dayton NCI Community Oncology Research Program
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lima, Ohio, United States, 45801
      • Saint Rita's Medical Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center Strongsville
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital/Foster J Boyd Regional Cancer Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Family Health and Surgery Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Cancer Care Associates
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
      • UPMC Hillman Cancer Center Erie
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Medical Group PC-Robert Packer Hospital
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Kent Hospital
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Charleston, South Carolina, United States, 29401
      • Roper Hospital
    • Easley, South Carolina, United States, 29640
      • Prisma Health Cancer Institute - Easley
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
    • Greenville, South Carolina, United States, 29601
      • Greenville Health System Cancer Institute-Andrews
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
    • West Columbia, South Carolina, United States, 29169
      • Lexington Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Medical Center
    • Nashville, Tennessee, United States, 37208
      • Meharry Medical College
    • Nashville, Tennessee, United States, 37203
      • Nashville Oncology Associates PC
  • Texas
    • Laredo, Texas, United States, 78041
      • Doctor's Hospital of Laredo
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center-Lubbock
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Fredericksburg, Virginia, United States, 22408
      • Hematology Oncology Associates of Fredericksburg Inc
    • Lynchburg, Virginia, United States, 24501
      • Centra Alan B Pearson Regional Cancer Center
  • Washington
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Auburn, Washington, United States, 98001
      • MultiCare Auburn Medical Center
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Kirkland, Washington, United States, 98033
      • EvergreenHealth Medical Center
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Olympia, Washington, United States, 98506-5166
      • Providence - Saint Peter Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Puyallup, Washington, United States, 98372
      • MultiCare Good Samaritan Hospital
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98104
      • Pacific Medical Center-First Hill
    • Sedro-Woolley, Washington, United States, 98284
      • PeaceHealth United General Medical Center
    • Silverdale, Washington, United States, 98383
      • Saint Michael Cancer Center
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center and Children's Hospital
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99208
      • Providence Holy Family Hospital
    • Tacoma, Washington, United States, 98405
      • MultiCare Tacoma General Hospital
    • Tacoma, Washington, United States, 98405
      • MultiCare Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • Northwest NCI Community Oncology Research Program
    • Tacoma, Washington, United States, 98405
      • Saint Joseph Medical Center
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • West Virginia
    • Huntington, West Virginia, United States, 25702
      • Saint Mary's Medical Center
    • Parkersburg, West Virginia, United States, 26101
      • Camden Clark Medical Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Milwaukee, Wisconsin, United States, 53210
      • Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologic confirmation of invasive breast cancer; patients with inflammatory breast cancer are not eligible

• Clinical stage II-III operable invasive breast cancer with intent to perform surgical resection after neoadjuvant therapy

  • Patients with multicentric or bilateral disease are eligible as long as the target lesion meets the eligibility criteria for this study
  • Staging to rule out metastatic disease is recommended for clinical stage III patients
• Tumors must be HER2 positive defined as HER2 3+ by immunohistochemical (IHC) assays or gene amplification by fluorescence in situ hybridization (FISH) with a ratio of >= 2 on invasive tumor
• Estrogen receptor (ER) and progesterone receptor (PgR) status must be known
• The target lesion in the breast must be >= 1 cm on physical examination or by radiographic measurement; palpable axillary adenopathy will be documented but not serve as measurable disease for the primary endpoint; patients with axillary disease only are not eligible to participate
• Patient agrees to provide pretreatment biopsies
• No prior chemotherapy, hormone therapy, biologic, or radiation therapy with therapeutic intent for this cancer
• Cardiac ejection fraction must be >= 50% by echocardiogram or multiple gated acquisition (MUGA) scan
• Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
• Patients must not be pregnant or nursing
• Absolute neutrophil count (ANC) >= 1,000/ul
• Platelet count >= 100,000/ul
• Bilirubin =< 1.5 times upper limit of normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN)
• Serum beta-human chorionic gonadotropin (HCG) negative (in female patients unless status-post (s/p) hysterectomy or menopausal or no menses for 24 consecutive months); assay must have a sensitivity of at least 50 mIU/mL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (THL); Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Trastuzumab; Given IV; Other Names: Herceptin; ABP 980; ALT02; Herceptin Biosimilar PF-05280014; Herceptin Trastuzumab Biosimilar PF-05280014; Herzuma; Ogivri; Ontruzant; PF-05280014; rhuMAb HER2; RO0452317; SB3; Trastuzumab Biosimilar ABP 980; Trastuzumab Biosimilar ALT02; trastuzumab biosimilar EG12014; Trastuzumab Biosimilar HLX02; Trastuzumab Biosimilar PF-05280014; Trastuzumab Biosimilar SB3; Trastuzumab-dkst; Trastuzumab-dttb; Trastuzumab-pkrb; Trazimera; Kanjinti; Trastuzumab Biosimilar SIBP-01; Trastuzumab-anns; Trastuzumab-qyyp; Herclon; Zercepac; QL 1701; QL-1701; QL1701; Trastuzumab Biosimilar QL1701; CT-P06; CT-P6; Trastuzumab Biosimilar CT-P6; Biceltis; CANMab; Hertraz; Hercessi; Trastuzumab-strf; Herwenda; Trastuzumab-herw; Trastuzumab-zerc; HLX 02; HLX-02; HLX02; PF 05280014; PF05280014; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Lapatinib Ditosylate; Given PO; Other Names: Tykerb
Active Comparator: Arm II (TH); Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Trastuzumab; Given IV; Other Names: Herceptin; ABP 980; ALT02; Herceptin Biosimilar PF-05280014; Herceptin Trastuzumab Biosimilar PF-05280014; Herzuma; Ogivri; Ontruzant; PF-05280014; rhuMAb HER2; RO0452317; SB3; Trastuzumab Biosimilar ABP 980; Trastuzumab Biosimilar ALT02; trastuzumab biosimilar EG12014; Trastuzumab Biosimilar HLX02; Trastuzumab Biosimilar PF-05280014; Trastuzumab Biosimilar SB3; Trastuzumab-dkst; Trastuzumab-dttb; Trastuzumab-pkrb; Trazimera; Kanjinti; Trastuzumab Biosimilar SIBP-01; Trastuzumab-anns; Trastuzumab-qyyp; Herclon; Zercepac; QL 1701; QL-1701; QL1701; Trastuzumab Biosimilar QL1701; CT-P06; CT-P6; Trastuzumab Biosimilar CT-P6; Biceltis; CANMab; Hertraz; Hercessi; Trastuzumab-strf; Herwenda; Trastuzumab-herw; Trastuzumab-zerc; HLX 02; HLX-02; HLX02; PF 05280014; PF05280014; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat
Experimental: Arm III (TL); Patients receive paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)	Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Lapatinib Ditosylate; Given PO; Other Names: Tykerb

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR Rate	Complete pathological response is defined as the absence of residual invasive carcinoma in the breast at the time of definitive surgical removal. Pathologic complete response in the lymph nodes is defined as no detectable invasive tumor by H&E. Analysis will use a chi-square test for the difference in proportions of patients on the THL arm versus the TH arm who achieve a pCR. Exact binomial methods will be used to construct 95% confidence intervals around the pCR incidence for each arm.	At time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Stage in the Breast and Axilla	Stage will be determined by the American Joint Committee on Cancer (AJCC) TNM (tumor, lymph nodes, metastasis) staging system.	At time of surgery
Radiographic Response Rate (at Completion of Neoadjuvant Therapy)	Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a complete response (disappearance of all target lesions) or partial response (30% decrease in sum of longest diameter of target lesions).	Week 16
Overall Survival	Overall survival was measured as the interval from study entry until death, from any cause, or last contact. Distribution was estimated using the Kaplan Meier product-limit method	Time from randomization to death or last follow-up (up to 10 years)
Relapse-free Survival (RFS)	Relapse free survival is defined as the interval from definitive surgery to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, or death from any cause, whichever occurs first. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Patients who do not undergo definitive surgery will not be assessable for RFS. Distribution was estimated using the Kaplan Meier product-limit method.	Time from surgery to any recurrence (up to 10 years)
Time to First Failure	Time to first failure is defined as the interval from study entry to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence or death from any cause. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Distribution was estimated using the Kaplan Meier product-limit method.	Time from study entry to any recurrence ( up to 10 years)
Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3	The type and grade of treatment-related toxicity will be tabulated by treatment arm.	Up to 30 days post-treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lisa A Carey, Alliance for Clinical Trials in Oncology

Publications and helpful links

General Publications

• Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. doi: 10.1200/JCO.20.01276. Epub 2020 Oct 23.
• Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. doi: 10.1200/JCO.2015.62.1268. Epub 2015 Nov 2.

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2009
• Primary Completion (Actual): January 31, 2014
• Study Completion (Actual): February 15, 2024

Study Registration Dates

• First Submitted: October 9, 2008
• First Submitted That Met QC Criteria: October 9, 2008
• First Posted (Estimated): October 10, 2008

Study Record Updates

• Last Update Posted (Actual): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Trastuzumab; Albumin-Bound Paclitaxel; Trastuzumab biosimilar HLX02; Lapatinib; Paclitaxel
• Other Study ID Numbers: NCI-2009-01073 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000616648; CALGB 40601 (Other Identifier: Alliance for Clinical Trials in Oncology); CALGB-40601 (Other Identifier: CTEP)