Doxorubicin Hydrochloride, Cyclophosphamide, and Pacltaxel With or Without Trastuzumab in Treating Women With HER2-Positive Node-Positive or High-Risk Node-Negative Breast Cancer

Stage IIIA Breast Cancer AJCC v7 Clinical Trial

Official title:

Phase III Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for Women With HER-2 Over-Expressing or Amplified Node Positive or High-Risk Node Negative Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005970
• Other study ID #: NCI-2012-01849
• Secondary ID: NCI-2012-0184993
• Status: Completed
• Phase: Phase 3
• Start date: May 19, 2000
• Est. completion date: January 27, 2010

Study information

• Verified date: August 2020
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and trastuzumab to see how well they work compared to combination chemotherapy alone in treating women with breast cancer that is human epidermal growth factor receptor 2 (HER2)-positive and has spread to the lymph nodes or high-risk and has not spread to the lymph nodes. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer.

Description:

PRIMARY OBJECTIVES:

I. To compare the combination of doxorubicin hydrochloride and cyclophosphamide (AC) followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of disease free survival (DFS). (Stage I) II. To compare the combination of AC followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of the rate of cardiac events. (Stage I) III. To compare the combination AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of DFS. (Stage II) IV. To compare the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of DFS. (Stage II) V. To compare the combination AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of the rate of cardiac events. (Stage II)

SECONDARY OBJECTIVES:

I. To compare the combination of AC followed by weekly paclitaxel with the sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of overall survival (OS).

II. To compare the combination AC followed by weekly paclitaxel with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of OS.

III. To compare the sequential schedule of the combination AC, weekly paclitaxel, and trastuzumab with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in terms of OS.

TERTIARY OBJECTIVES:

I. To determine whether higher levels of shed ECD (extracellular domain) or autoantibodies to human epidermal growth factor receptor (HER)-2 and HER-1 measured in the serum prior to treatment are prognostic for DFS and survival.

II. To determine the concordance of central review of HER-2 overexpression as measured by the HercepTest (DAKO) and Vysis fluorescence in situ hybridization (FISH).

III. For each treatment arm, levels of brain natriuretic peptide (BNP), troponin-T (TnT), troponin-I (cTnI), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-6 (IL-6), CD40 ligand, and troponin levels will be compared and contrasted.

IV. To determine whether genetic markers are prognostic for cardiac adverse events associated with treatment.

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

ARM I*: Patients receive doxorubicin hydrochloride intravenously (IV) and cyclophosphamide IV over 20-30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel IV over 1 hour beginning on day 1 of week 13 and continuing weekly for 12 courses in the absence of disease progression or unacceptable toxicity. NOTE: *Patients who completed paclitaxel on or after October 25, 2004 may receive trastuzumab for a maximum of 52 weeks either concurrently with paclitaxel or following completion of paclitaxel treatment.

ARM II*: Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab IV over 30-90 minutes beginning on day 1 of week 25 and continuing weekly for 52 courses in the absence of disease progression or unacceptable toxicity. NOTE: *Patients who completed paclitaxel on or after October 25, 2004 may receive trastuzumab for a maximum of 52 weeks either concurrently with paclitaxel or following completion of paclitaxel treatment.

ARM III: Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I. Patients then receive paclitaxel IV over 1 hour and trastuzumab IV over 30-90 minutes beginning on day 1 of week 13 and continuing weekly for 12 courses. Patients then receive trastuzumab IV over 30 minutes beginning on day 1 of week 25 and continuing weekly for 40 courses in the absence of disease progression or unacceptable toxicity.

Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal estrogen receptor (ER)- or progesterone receptor (PR)-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 15 years or until disease progression.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3436
• Est. completion date: January 27, 2010
• Est. primary completion date: April 25, 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Required tumor parameters for node positive disease: NOTE: This study will continue to use the American Joint Committee on Cancer (AJCC) 5th edition for TNM classification and staging

• Operable, histologically confirmed adenocarcinoma of the female breast and positive lymph nodes

• Node positivity may be determined by either an axillary node dissection or a positive sentinel node finding by hematoxylin and eosin (H&E)

• NOTE: Positive nodes refers to H&E visible nodal metastases; immunohistochemistry (IHC) positive only cells in lymph nodes will not be considered positive nodes

• One or more positive lymph nodes whose tumors are T1-3, pN1-2, M0 are eligible

• cN2 disease is not eligible

• pN2 disease is eligible

• One positive lymph node by sentinel node biopsy or at least 6 axillary nodes must be examined on axillary node dissection with at least one positive lymph node

• Metaplastic carcinoma is eligible

• ER/PgR determination

• HER-2 positive (pre-entry requirement for registration)

• FISH must show gene amplification OR

• IHC assay must show a strong positive (3+) staining score

• NOTE: ductal carcinoma in situ (DCIS) components should not be counted in the determination of degree of IHC staining or FISH amplification

• Required tumor parameters for high-risk node-negative disease; NOTE: This study will continue to use the AJCC 5th edition for TNM classification and staging

• Operable, histologically confirmed adenocarcinoma of the female breast and negative lymph nodes

• Node status may be determined by either axillary node dissection or sentinel node biopsy with H&E staining; to be considered node negative, either of the following must be true: 1) negative sentinel node biopsy or 2) no positive lymph nodes found among at least 6 axillary nodes examined on axillary node dissection

• NOTE: IHC positive only cells in lymph nodes will not be considered positive nodes

• Tumors > 2.0 cm (irrespective of hormonal receptor status) or > 1.0 cm if ER-negative and PR-negative disease

• ER/PgR determination

• HER-2 positive (pre-entry requirement for registration)

• FISH must show gene amplification OR

• IHC assay must show a strong positive (3+) staining score

• NOTE: DCIS components should not be counted in the determination of degree of IHC staining or FISH amplification

• =< 84 days from mastectomy or =< 84 days from axillary dissection or sentinel node detection if the patient's most extensive breast surgery was a breast sparing procedure; (This timing is per a decision by the Breast Intergroup)

• Surgical resection margins. All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy with axillary node dissection

• Mastectomy: There will be no evidence of gross or microscopic tumor (invasive or DCIS) at the surgical resection margins noted in the final surgery or pathology reports; patients with close margins are eligible

• Segmental mastectomy (lumpectomy): Margins must be clear of invasive cancer and DCIS

• Axillary dissection or sentinel node dissection: There will be no gross residual adenopathy

• TAM therapy

• May have received up to four weeks of TAM therapy, or any other hormonal agent, for this malignancy

• May have received TAM or raloxifene for purposes of chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (including previous breast cancer if lobular carcinoma in situ [LCIS]) but must be discontinued before registration on this study

• May never have received TAM, raloxifene, or any other hormonal agent

• Absolute neutrophil count (ANC) >= 1500/mm^3

• Platelets (PLT) >= 100,000/mm^3

• Total bilirubin =< 1.5 x upper normal limit (UNL)

• Aspartate aminotransferase (AST) =< 2.0 x UNL

• Left ventricular ejection fraction (LVEF) within institutional normal range; if LVEF is > 75%, the investigator should consider performing a second review of the multigated acquisition (MUGA)/echocardiogram or performing a repeat MUGA/echocardiogram prior to registration; such re-reviews or repeat MUGA/echocardiogram are not permitted after registration

• Willingness to discontinue sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc., prior to registration and while on study

• Willingness to discontinue any hormonal agent such as raloxifene (Evista) prior to registration and while on study

• Non-breast malignancies that have not recurred within the last 5 years and are deemed to be at low risk for recurrence

EXCEPTIONS: These non-breast malignancies are eligible even if diagnosed =< 5 years prior to registration:

• Squamous or basal cell carcinoma of the skin that has been effectively treated

• Carcinoma in situ of the cervix that has been treated by surgery only

• Lobular carcinoma in situ (LCIS) of the ipsilateral or contralateral breast treated by surgery and/or tamoxifen only

• Patients undergoing breast conservation therapy (i.e., lumpectomy and axillary dissection) must have plans to receive radiation therapy to the breast +/- regional lymphatics following completion of the chemotherapy; for patients treated with mastectomy, the use of radiation therapy is required for 4 or more positive lymph nodes and must be started after completion of chemotherapy; the use of radiation therapy is at the discretion of the investigator for 0-3 positive lymph nodes but, if used, must be started after the completion of chemotherapy

• Prior to registration, the physician must designate if it is planned for the patient to receive radiation therapy (for adjuvant radiation therapy post-mastectomy or, less commonly, post-conservative therapy but not primary breast radiation as part of breast conserving treatment)

• Willing and able to sign an informed consent

• Gene amplified by FISH or strong positivity (3+) by HercepTest on central review; Note: The patient registers based on community HER-2 testing using FISH or IHC, AC chemotherapy is initiated; the tumor block or slides must be received =< 2 weeks from time of registration to the North Central Cancer Treatment Group (NCCTG) Operations Office for central HER-2 testing

Exclusion Criteria:

• Any of the following:

• Pregnant women

• Nursing women

• Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, intrauterine device [IUD], surgical sterilization, or abstinence, etc.); hormonal birth control methods are not permitted

• Locally advanced tumors (classification T4) at diagnosis including tumors fixed to chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)

• Prior history of breast cancer, except LCIS

• Bilateral invasive carcinoma, either metachronous or synchronous (EXCEPTION: Patients diagnosed with unilateral invasive carcinoma and metachronous or synchronous DCIS of the contralateral breast treated with mastectomy are eligible)

• Prior chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer

• Active, unresolved infection

• Active cardiac disease

• Any prior myocardial infarction

• History of documented congestive heart failure (CHF)

• Current use of digitalis or beta-blockers for CHF

• Any prior history of arrhythmia or cardiac valvular disease requiring medications or clinically significant

• Current use of medications for treatment of arrhythmias or angina pectoris

• Current uncontrolled hypertension (diastolic > 100 mmHg or systolic > 200 mmHg)

• Clinically significant pericardial effusion

• Prior anthracycline or taxane therapy for any malignancy

• Sensitivity to benzyl alcohol

• Neurology/Neuropathy-Sensory >= grade 2 per the National Cancer Institute's (NCI's) Common Toxicity Criteria Version 2.0; EXCEPTION: Any chronic neurologic disorder will be looked at on a case-by-case basis by the study chair

Related Conditions & MeSH terms

• Breast Adenocarcinoma
• Breast Neoplasms
• HER2 Positive Breast Carcinoma
• Stage IA Breast Cancer AJCC v7
• Stage IB Breast Cancer AJCC v7
• Stage IIA Breast Cancer AJCC v6 and v7
• Stage IIB Breast Cancer AJCC v6 and v7
• Stage IIIA Breast Cancer AJCC v7

Intervention

Drug:
• Aromatase Inhibition Therapy
Given orally
• Cyclophosphamide
Given IV
• Doxorubicin Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Paclitaxel
Given IV
• Tamoxifen Citrate
Given orally

Biological:
• Trastuzumab
Given IV

Locations

Country	Name	City	State
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
South Africa	University Of Pretoria	Pretoria
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Mission Hospital Inc-Memorial Campus	Asheville	North Carolina
United States	Atlanta Regional CCOP	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Southwestern Vermont Medical Center	Bennington	Vermont
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	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	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	Sentara Martha Jefferson Hospital	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Community Cancer Institute	Clovis	California
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	University of Oregon	Eugene	Oregon
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Washington Hospital	Fremont	California
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	University of Texas Medical Branch	Galveston	Texas
United States	Glendale Memorial Hospital and Health Center	Glendale	California
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Milford Regional Medical Center	Milford	Massachusetts
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Memorial Medical Center	Modesto	California
United States	Community Hospital of Monterey Peninsula	Monterey	California
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Western Regional CCOP	Phoenix	Arizona
United States	Via Christi Hospital-Pittsburg	Pittsburg	Kansas
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Washington University - Jewish	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Salina Regional Health Center	Salina	Kansas
United States	Salinas Valley Memorial	Salinas	California
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Naval Medical Center -San Diego	San Diego	California
United States	University of California San Diego	San Diego	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	The Angeles Clinic and Research Institute - Santa Monica Office	Santa Monica	California
United States	Santa Rosa Memorial Hospital	Santa Rosa	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Sanford NCI Community Oncology Research Program of the North Central Plains	Sioux Falls	South Dakota
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	SUNY Upstate Medical Center-Community Campus	Syracuse	New York
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Wilson Medical Center	Wilson	North Carolina
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Southeast Clinical Oncology Research (SCOR) Consortium NCORP	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Saint Vincent Hospital/Reliant Medical Group	Worcester	Massachusetts
United States	University of Massachusetts Medical School	Worcester	Massachusetts
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (5)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Canadian Cancer Trials Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Southwest Oncology Group

Countries where clinical trial is conducted

United States,  Canada,  Peru,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of DFS	Will be estimated using the Kaplan-Meier method. A stratified log-rank test will be used to assess whether DFS differs with respect to the addition of trastuzumab to a chemotherapy regimen including AC and paclitaxel. Ninety-five percent confidence intervals will be reported for relative risks, for DFS at the 5-year point, and for absolute benefit as defined by differences in DFS and OS.	Time from registration to first adverse event, assessed up to 15 years
Secondary	Overall survival	Will be estimated using the Kaplan-Meier method. A stratified log-rank test will be used to assess whether OS differs with respect to the addition of trastuzumab to a chemotherapy regimen including AC and paclitaxel. Ninety-five percent confidence intervals will be reported for relative risks, for OS at the 5-year point, and for absolute benefit as defined by differences in DFS and OS.	Time from registration to death due to any cause, assessed up to 15 years