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

NCT ID: NCT00005970

Last Updated: 2020-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3436 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-05-19

Study Completion Date

2010-01-27

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Breast Adenocarcinoma 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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (AC, paclitaxel, tamoxifen, aromatase inhibitor)

Patients receive doxorubicin hydrochloride 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. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or 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.

Group Type EXPERIMENTAL

Aromatase Inhibition Therapy

Intervention Type DRUG

Given orally

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

Tamoxifen Citrate

Intervention Type DRUG

Given orally

Arm II (AC, paclitaxel, trastuzumab, tamoxifen)

Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in arm I. Patients then receive trastuzumab (Herceptin®) 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. Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or 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.

Group Type EXPERIMENTAL

Aromatase Inhibition Therapy

Intervention Type DRUG

Given orally

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

Tamoxifen Citrate

Intervention Type DRUG

Given orally

Trastuzumab

Intervention Type BIOLOGICAL

Given IV

Arm III (AC, paclitaxel, trastuzumab, tamoxifen)

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 ER- or 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.

Group Type EXPERIMENTAL

Aromatase Inhibition Therapy

Intervention Type DRUG

Given orally

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

Tamoxifen Citrate

Intervention Type DRUG

Given orally

Trastuzumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Aromatase Inhibition Therapy

Given orally

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Paclitaxel

Given IV

Intervention Type DRUG

Tamoxifen Citrate

Given orally

Intervention Type DRUG

Trastuzumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Aromatase Inhibition (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin HCl Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Apo-Tamox Clonoxifen Dignotamoxi Ebefen Emblon Estroxyn Fentamox Gen-Tamoxifen Genox ICI 46,474 ICI-46474 Jenoxifen Kessar Ledertam Lesporene Nolgen Noltam Nolvadex Nolvadex-D Nourytam Novo-Tamoxifen Novofen Noxitem Oestrifen Oncotam PMS-Tamoxifen Soltamox TAM Tamax Tamaxin Tamifen Tamizam Tamofen Tamoxasta Tamoxifeni Citras Zemide ABP 980 ALT02 Anti-c-ERB-2 Anti-c-erbB2 Monoclonal Antibody Anti-ERB-2 Anti-erbB-2 Anti-erbB2 Monoclonal Antibody Anti-HER2/c-erbB2 Monoclonal Antibody Anti-p185-HER2 c-erb-2 Monoclonal Antibody HER2 Monoclonal Antibody Herceptin Herceptin Biosimilar PF-05280014 Herceptin Trastuzumab Biosimilar PF-05280014 Herzuma MoAb HER2 Monoclonal Antibody c-erb-2 Monoclonal Antibody HER2 Ogivri Ontruzant PF-05280014 rhuMAb HER2 RO0452317 Trastuzumab Biosimilar ABP 980 Trastuzumab Biosimilar ALT02 trastuzumab biosimilar EG12014 Trastuzumab Biosimilar HLX02 Trastuzumab Biosimilar PF-05280014 Trastuzumab-dkst Trastuzumab-DTTB Trastuzumab-pkrb Trastuzumab-QYYP Trazimera

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Cancer and Leukemia Group B

NETWORK

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Edith A Perez

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

Western Regional CCOP

Phoenix, Arizona, United States

Site Status

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Community Cancer Institute

Clovis, California, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Washington Hospital

Fremont, California, United States

Site Status

Glendale Memorial Hospital and Health Center

Glendale, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Memorial Medical Center

Modesto, California, United States

Site Status

Community Hospital of Monterey Peninsula

Monterey, California, United States

Site Status

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Salinas Valley Memorial

Salinas, California, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

Naval Medical Center -San Diego

San Diego, California, United States

Site Status

UCSF Medical Center-Mount Zion

San Francisco, California, United States

Site Status

The Angeles Clinic and Research Institute - Santa Monica Office

Santa Monica, California, United States

Site Status

Santa Rosa Memorial Hospital

Santa Rosa, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

MedStar Georgetown University Hospital

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

Site Status

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Atlanta Regional CCOP

Atlanta, Georgia, United States

Site Status

Northeast Georgia Medical Center-Gainesville

Gainesville, Georgia, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Heartland Cancer Research NCORP

Decatur, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Site Status

Iowa-Wide Oncology Research Coalition NCORP

Des Moines, Iowa, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Siouxland Regional Cancer Center

Sioux City, Iowa, United States

Site Status

Via Christi Hospital-Pittsburg

Pittsburg, Kansas, United States

Site Status

Kansas City NCI Community Oncology Research Program

Prairie Village, Kansas, United States

Site Status

Salina Regional Health Center

Salina, Kansas, United States

Site Status

Cotton O'Neil Cancer Center / Stormont Vail Health

Topeka, Kansas, United States

Site Status

Saint Francis Hospital and Medical Center - Topeka

Topeka, Kansas, United States

Site Status

Wichita NCI Community Oncology Research Program

Wichita, Kansas, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

Louisiana State University Health Sciences Center Shreveport

Shreveport, Louisiana, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Milford Regional Medical Center

Milford, Massachusetts, United States

Site Status

Saint Vincent Hospital/Reliant Medical Group

Worcester, Massachusetts, United States

Site Status

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Site Status

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, United States

Site Status

Kalamazoo Center for Medical Studies

Kalamazoo, Michigan, United States

Site Status

Ascension Providence Hospitals - Southfield

Southfield, Michigan, United States

Site Status

Essentia Health Cancer Center

Duluth, Minnesota, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, United States

Site Status

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Site Status

Cancer Research for the Ozarks NCORP

Springfield, Missouri, United States

Site Status

Washington University - Jewish

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status

Saint Louis-Cape Girardeau CCOP

St Louis, Missouri, United States

Site Status

Montana Cancer Consortium NCORP

Billings, Montana, United States

Site Status

CHI Health Good Samaritan

Kearney, Nebraska, United States

Site Status

Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

New Hampshire Oncology Hematology PA-Hooksett

Hooksett, New Hampshire, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Englewood Hospital and Medical Center

Englewood, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status

Mount Sinai Hospital

New York, New York, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

SUNY Upstate Medical Center-Community Campus

Syracuse, New York, United States

Site Status

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, United States

Site Status

Mission Hospital Inc-Memorial Campus

Asheville, North Carolina, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cone Health Cancer Center

Greensboro, North Carolina, United States

Site Status

Wilson Medical Center

Wilson, North Carolina, United States

Site Status

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, United States

Site Status

Southeast Clinical Oncology Research (SCOR) Consortium NCORP

Winston-Salem, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States

Site Status

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Site Status

Altru Cancer Center

Grand Forks, North Dakota, United States

Site Status

University of Cincinnati/Barrett Cancer Center

Cincinnati, Ohio, United States

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Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Toledo Community Hospital Oncology Program CCOP

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

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University of Oregon

Eugene, Oregon, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

West Penn Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Site Status

Memorial Hospital of Rhode Island

Pawtucket, Rhode Island, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Roper Hospital

Charleston, South Carolina, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Site Status

Sanford NCI Community Oncology Research Program of the North Central Plains

Sioux Falls, South Dakota, United States

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Wellmont Holston Valley Hospital and Medical Center

Kingsport, Tennessee, United States

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Thompson Cancer Survival Center

Knoxville, Tennessee, United States

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University of Tennessee - Knoxville

Knoxville, Tennessee, United States

Site Status

University of Tennessee Health Science Center

Memphis, Tennessee, United States

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Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

The Don and Sybil Harrington Cancer Center

Amarillo, Texas, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

Southwestern Vermont Medical Center

Bennington, Vermont, United States

Site Status

University of Vermont and State Agricultural College

Burlington, Vermont, United States

Site Status

Sentara Martha Jefferson Hospital

Charlottesville, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Kaiser Permanente Washington

Seattle, Washington, United States

Site Status

Northwest NCI Community Oncology Research Program

Tacoma, Washington, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Site Status

Instituto Nacional de Enfermedades Neoplasicas

Lima, , Peru

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University Of Pretoria

Pretoria, , South Africa

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Countries

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United States Canada Peru South Africa

References

Explore related publications, articles, or registry entries linked to this study.

Chumsri S, Pai T, Ma Y, Li Z, Gil A, Moreno-Aspitia A, Colon-Otero G, Pogue-Geile KL, Rasgoti P, Paik S, Perez EA, Thompson EA. Clinical Treatment Score Post-5 Years (CTS5) and Late Recurrence Risk in Hormone Receptor-Positive, HER2-Positive Breast Cancer. J Natl Compr Canc Netw. 2024 Aug 26;22(7):463-468. doi: 10.6004/jnccn.2024.7015.

Reference Type DERIVED
PMID: 39191270 (View on PubMed)

Chumsri S, Li Z, Serie DJ, Norton N, Mashadi-Hossein A, Tenner K, Brauer HA, Warren S, Danaher P, Colon-Otero G, Partridge AH, Carey LA, Hilbers F, Van Dooren V, Holmes E, Di Cosimo S, Werner O, Huober JB, Dueck AC, Sotiriou C, Saura C, Moreno-Aspitia A, Knutson KL, Perez EA, Thompson EA. Adaptive immune signature in HER2-positive breast cancer in NCCTG (Alliance) N9831 and NeoALTTO trials. NPJ Breast Cancer. 2022 May 24;8(1):68. doi: 10.1038/s41523-022-00430-0.

Reference Type DERIVED
PMID: 35610260 (View on PubMed)

Caparica R, Ma Y, De Angelis C, Richard F, Desmedt C, Awada A, Piccart M, Perez EA, Moreno-Aspitia A, Badve S, Thompson EA, de Azambuja E. Beta-2 Adrenergic Receptor Gene Expression in HER2-Positive Early-Stage Breast Cancer Patients: A Post-hoc Analysis of the NCCTG-N9831 (Alliance) Trial. Clin Breast Cancer. 2022 Jun;22(4):308-318. doi: 10.1016/j.clbc.2021.11.012. Epub 2021 Dec 2.

Reference Type DERIVED
PMID: 34980541 (View on PubMed)

Chumsri S, Li Z, Serie DJ, Mashadi-Hossein A, Colon-Otero G, Song N, Pogue-Geile KL, Gavin PG, Paik S, Moreno-Aspitia A, Perez EA, Thompson EA. Incidence of Late Relapses in Patients With HER2-Positive Breast Cancer Receiving Adjuvant Trastuzumab: Combined Analysis of NCCTG N9831 (Alliance) and NRG Oncology/NSABP B-31. J Clin Oncol. 2019 Dec 10;37(35):3425-3435. doi: 10.1200/JCO.19.00443. Epub 2019 Oct 17.

Reference Type DERIVED
PMID: 31622131 (View on PubMed)

Chumsri S, Serie DJ, Li Z, Pogue-Geile KL, Soyano-Muller AE, Mashadi-Hossein A, Warren S, Lou Y, Colon-Otero G, Knutson KL, Perez EA, Moreno-Aspitia A, Thompson EA. Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials. Clin Cancer Res. 2019 Jul 15;25(14):4422-4430. doi: 10.1158/1078-0432.CCR-18-2206. Epub 2019 Feb 26.

Reference Type DERIVED
PMID: 30808774 (View on PubMed)

Norton N, Fox N, McCarl CA, Tenner KS, Ballman K, Erskine CL, Necela BM, Northfelt D, Tan WW, Calfa C, Pegram M, Colon-Otero G, Perez EA, Clynes R, Knutson KL. Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer. Breast Cancer Res. 2018 Jun 14;20(1):52. doi: 10.1186/s13058-018-0989-8.

Reference Type DERIVED
PMID: 29898752 (View on PubMed)

Perez EA, Ballman KV, Tenner KS, Thompson EA, Badve SS, Bailey H, Baehner FL. Association of Stromal Tumor-Infiltrating Lymphocytes With Recurrence-Free Survival in the N9831 Adjuvant Trial in Patients With Early-Stage HER2-Positive Breast Cancer. JAMA Oncol. 2016 Jan;2(1):56-64. doi: 10.1001/jamaoncol.2015.3239.

Reference Type DERIVED
PMID: 26469139 (View on PubMed)

Perez EA, Baehner FL, Butler SM, Thompson EA, Dueck AC, Jamshidian F, Cherbavaz D, Yoshizawa C, Shak S, Kaufman PA, Davidson NE, Gralow J, Asmann YW, Ballman KV. The relationship between quantitative human epidermal growth factor receptor 2 gene expression by the 21-gene reverse transcriptase polymerase chain reaction assay and adjuvant trastuzumab benefit in Alliance N9831. Breast Cancer Res. 2015 Oct 1;17(1):133. doi: 10.1186/s13058-015-0643-7.

Reference Type DERIVED
PMID: 26429296 (View on PubMed)

O'Sullivan CC, Bradbury I, Campbell C, Spielmann M, Perez EA, Joensuu H, Costantino JP, Delaloge S, Rastogi P, Zardavas D, Ballman KV, Holmes E, de Azambuja E, Piccart-Gebhart M, Zujewski JA, Gelber RD. Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer and Tumors </= 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials. J Clin Oncol. 2015 Aug 20;33(24):2600-8. doi: 10.1200/JCO.2015.60.8620. Epub 2015 Jun 22.

Reference Type DERIVED
PMID: 26101239 (View on PubMed)

Perez EA, Thompson EA, Ballman KV, Anderson SK, Asmann YW, Kalari KR, Eckel-Passow JE, Dueck AC, Tenner KS, Jen J, Fan JB, Geiger XJ, McCullough AE, Chen B, Jenkins RB, Sledge GW, Winer EP, Gralow JR, Reinholz MM. Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the North Central Cancer Treatment Group n9831 Adjuvant Trastuzumab Trial. J Clin Oncol. 2015 Mar 1;33(7):701-8. doi: 10.1200/JCO.2014.57.6298. Epub 2015 Jan 20.

Reference Type DERIVED
PMID: 25605861 (View on PubMed)

Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. doi: 10.1200/JCO.2014.55.5730. Epub 2014 Oct 20.

Reference Type DERIVED
PMID: 25332249 (View on PubMed)

Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. doi: 10.1200/JCO.2011.36.7045. Epub 2011 Oct 31.

Reference Type DERIVED
PMID: 22042958 (View on PubMed)

Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. doi: 10.1056/NEJMoa052122.

Reference Type DERIVED
PMID: 16236738 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2012-01849

Identifier Type: REGISTRY

Identifier Source: secondary_id

9343

Identifier Type: -

Identifier Source: secondary_id

ECOG-N9831

Identifier Type: -

Identifier Source: secondary_id

CAN-NCIC-MA28

Identifier Type: -

Identifier Source: secondary_id

SWOG-N9831

Identifier Type: -

Identifier Source: secondary_id

MA.28

Identifier Type: -

Identifier Source: secondary_id

NCCTG-N9831

Identifier Type: -

Identifier Source: secondary_id

CALGB-49909

Identifier Type: -

Identifier Source: secondary_id

CDR0000067953

Identifier Type: -

Identifier Source: secondary_id

GUMC-00224

Identifier Type: -

Identifier Source: secondary_id

N9831

Identifier Type: OTHER

Identifier Source: secondary_id

N9831

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA025224

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01849

Identifier Type: -

Identifier Source: org_study_id

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