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

Stage IIIC Breast Cancer AJCC v7 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00770809
• Other study ID #: NCI-2009-01073
• Secondary ID: NCI-2009-01073CD
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 1, 2008
• Est. completion date: July 10, 2024

Study information

• Verified date: February 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 305
• Est. completion date: July 10, 2024
• Est. primary completion date: January 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• 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

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lapatinib Ditosylate
Given PO
• Paclitaxel
Given IV

Biological:
• Trastuzumab
Given IV

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hospital	San Juan
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Hematology Oncology Associates	Albuquerque	New Mexico
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint Anthony's Health	Alton	Illinois
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Mission Hospital	Asheville	North Carolina
United States	Atlanta Regional CCOP	Atlanta	Georgia
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Sturdy Memorial Hospital	Attleboro	Massachusetts
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	The Medical Center of Aurora	Aurora	Colorado
United States	WellStar Cobb Hospital	Austell	Georgia
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Cleveland Clinic Cancer Center Beachwood	Beachwood	Ohio
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Steward Saint Elizabeth's Medical Center	Brighton	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	Erlanger Medical Center	Chattanooga	Tennessee
United States	Mount Sinai Hospital Medical Center	Chicago	Illinois
United States	Presence Resurrection Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Weiss Memorial Hospital	Chicago	Illinois
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Danville Regional Medical Center	Danville	Virginia
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Halifax Health Medical Center-Centers for Oncology	Daytona Beach	Florida
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Dekalb Medical Center	Decatur	Georgia
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Elmhurst Hospital Center	Elmhurst	New York
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Swedish Medical Center	Englewood	Colorado
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Saint Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Sparks Regional Medical Center	Fort Smith	Arkansas
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Hematology Oncology Associates of Fredericksburg Inc	Fredericksburg	Virginia
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Florida Cancer Specialists-Gainesville Cancer Center	Gainesville	Florida
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Genesys Regional Medical Center	Grand Blanc	Michigan
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	East Carolina University	Greenville	North Carolina
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Northern Montana Hospital	Havre	Montana
United States	HaysMed	Hays	Kansas
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Saint Mary's Medical Center	Huntington	West Virginia
United States	Hutchinson Regional Medical Center	Hutchinson	Kansas
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Allegiance Health	Jackson	Michigan
United States	Queens Hospital Center	Jamaica	New York
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	ECU Health Oncology Kinston	Kinston	North Carolina
United States	EvergreenHealth Medical Center	Kirkland	Washington
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire
United States	Northwell Health NCORP	Lake Success	New York
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Doctor's Hospital of Laredo	Laredo	Texas
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Northside Hospital - Gwinnett	Lawrenceville	Georgia
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Texas Tech University Health Sciences Center-Lubbock	Lubbock	Texas
United States	Centra Alan B Pearson Regional Cancer Center	Lynchburg	Virginia
United States	Atrium Health Navicent	Macon	Georgia
United States	Dartmouth Cancer Center - Manchester	Manchester	New Hampshire
United States	Elliot Hospital	Manchester	New Hampshire
United States	Manchester Memorial Hospital	Manchester	Connecticut
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	North Shore University Hospital	Manhasset	New York
United States	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Garnet Health Medical Center	Middletown	New York
United States	Middlesex Hospital	Middletown	Connecticut
United States	Dana-Farber/Brigham and Women's Cancer Center at Milford Regional	Milford	Massachusetts
United States	Ascension Southeast Wisconsin Hospital - Saint Joseph Campus	Milwaukee	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Morristown Medical Center	Morristown	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	El Camino Hospital	Mountain View	California
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Foundation Medical Partners	Nashua	New Hampshire
United States	Meharry Medical College	Nashville	Tennessee
United States	Nashville Oncology Associates PC	Nashville	Tennessee
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Newton-Wellesley Hospital	Newton	Massachusetts
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Cancer Care Associates	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Providence - Saint Peter Hospital	Olympia	Washington
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Desert Regional Medical Center	Palm Springs	California
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Parker Adventist Hospital	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Vassar Brothers Medical Center	Poughkeepsie	New York
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	UNC Rex Healthcare	Raleigh	North Carolina
United States	Renown Regional Medical Center	Reno	Nevada
United States	Reid Health	Richmond	Indiana
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Swedish American Hospital	Rockford	Illinois
United States	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Saint Helena Hospital	Saint Helena	California
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Comprehensive Cancer Care PC	Saint Louis	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Salinas Valley Memorial	Salinas	California
United States	TidalHealth Peninsula Regional	Salisbury	Maryland
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Zuckerberg San Francisco General Hospital	San Francisco	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Medical Center-First Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Providence Holy Family Hospital	Spokane	Washington
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Overlook Hospital	Summit	New Jersey
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MultiCare Allenmore Hospital	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	North Suburban Medical Center	Thornton	Colorado
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Upper Valley Medical Center	Troy	Ohio
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Kent Hospital	Warwick	Rhode Island
United States	Marion L Shepard Cancer Center - ECU Health Beaufort Hospital	Washington	North Carolina
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Cleveland Clinic-Weston	Weston	Florida
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Clinton Memorial Hospital/Foster J Boyd Regional Cancer Center	Wilmington	Ohio
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Greene Memorial Hospital	Xenia	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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

External Links

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