Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

Stage IIIA Breast Cancer Clinical Trial

— SOFT  

Official title:

A Phase III Trial Evaluating the Role of Ovarian Function Suppression and the Role of Exemestane as Adjuvant Therapies for Premenopausal Women With Endocrine Responsive Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00066690
• Other study ID #: IBCSG 24-02 / BIG 2-02
• Secondary ID: NCI-2009-01086CD
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 17, 2003
• Est. completion date: December 2025

Study information

• Verified date: December 2023
• Source: ETOP IBCSG Partners Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Estrogen can stimulate the growth of breast tumor cells. Ovarian function suppression combined with hormone therapy using tamoxifen or exemestane may fight breast cancer by reducing the production of estrogen. It is not yet known whether suppression of ovarian function plus either tamoxifen or exemestane is more effective than tamoxifen alone in preventing the recurrence of hormone-responsive breast cancer.

PURPOSE: This randomized phase III trial studies ovarian suppression with either tamoxifen or exemestane to see how well they work compared to tamoxifen alone in treating premenopausal women who have undergone surgery for hormone-responsive breast cancer.

Description:

OBJECTIVES:

• Compare the disease-free survival, breast cancer-free interval, distant recurrence-free interval and overall survival of premenopausal women with endocrine-responsive breast cancer when treated with tamoxifen + ovarian function suppression (by triptorelin, oophorectomy, or ovarian irradiation) or exemestane + ovarian function suppression vs. tamoxifen alone. The primary comparison is ovarian function suppression with either tamoxifen or exemestane vs. tamoxifen alone.

• Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, prior adjuvant/neoadjuvant chemotherapy (yes vs no), and number of positive axillary and/or internal mammary lymph nodes (0 vs 1 or more) and intended initial method of ovarian function suppression (triptorelin vs oophorectomy vs ovarian irradiation). Treatment duration is 5 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4 years.

Other known NCT identifiers

• NCT00917969
• NCT02140190

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3066
• Est. completion date: December 2025
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Premenopausal women (estradiol [E2] in the premenopausal range [according to institution parameters]) who meet the following criteria:

• Patients who did not receive chemotherapy should be randomized within 12 weeks after definitive surgery; such patients should have estradiol (E2) in the premenopausal range following surgery; the only patients who do not require testing of estradiol (E2) to confirm premenopausal status are those who have been menstruating regularly during the 6 months prior to randomization and have not used any form of hormonal contraception or any other hormonal treatments during the 6 months prior to randomization

• Patients who received prior adjuvant and/or neoadjuvant chemotherapy should be randomized after completing chemotherapy and within 8 months of the final dose of chemotherapy as soon as premenopausal status is confirmed; all such patients should have premenopausal status confirmed by an estradiol (E2) in the premenopausal range between 2 weeks and 8 months after completing chemotherapy

• Adjuvant trastuzumab (Herceptin ®) is allowable, and is not considered to be chemotherapy for eligibility timing determination

• Patients with temporary chemotherapy-induced amenorrhea who regain premenopausal status within eight months of the final dose of chemotherapy are eligible; (please note that some patients taking tamoxifen or aromatase inhibitors, even without evidence of menses, may have ovarian function recovery following chemotherapy and resume estradiol secretion); in patients wishing to participate in the study, with postmenopausal hormone levels shortly after chemotherapy, it is recommended to recheck their estradiol level at a later timepoint within 8 months of completing chemotherapy, even in the absence of return of menses

• Histologically proven, resected breast cancer; pathology material should be available for submission for central review as part of the quality control measures for this protocol

• Patients must have hormone receptor positive tumors; if there is more than one breast tumor, each tumor must be hormone receptor positive; hormone receptors must be determined using immunohistochemistry; estrogen receptor (ER) and/or progesterone receptor (PgR) must be greater than or equal to 10% of the tumor cells positive by immunohistochemical evaluation; biochemical determination alone is not acceptable

• The tumor must be confined to the breast and axillary nodes without detected metastases elsewhere, with the exception of tumor detected in internal mammary chain nodes by sentinel node procedure; patients who received neoadjuvant therapy must have had operable disease prior to neoadjuvant treatment to be eligible; patients who had a pathological evaluation with tru cut or core biopsy of invasive breast cancer prior to neoadjuvant therapy and were found to have no invasive tumor in the pathological specimen from definitive surgery are eligible; for these patients, pre-neoadjuvant tumor characteristics will be used for defining eligibility; in case of persistent disease, pathology findings from the definitive surgery should be used

• Patients must have had proper surgery for primary breast cancer with no known clinical residual loco-regional disease:

• A total mastectomy; radiotherapy is optional after mastectomy OR

• A breast-conserving procedure (lumpectomy, quadrantectomy or partial mastectomy with margins clear of invasive cancer and ductal breast carcinoma in situ [DCIS]); the local pathologist must document negative margins of resection in the pathology report; if all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed; likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed; radiation therapy to the conserved breast is required; patients may be randomized before, during or after completion of radiation therapy to the breast

• Either axillary lymph node dissection (pathological examination of at least 6 nodes recommended) or a negative axillary sentinel node biopsy (pN0[sn]) is required; patients with negative or microscopically axillary positive sentinel nodes (pN1mi: micrometastasis none > 2.0 mm) do not require further axillary therapy; those with positive sentinel nodes must have either an axillary dissection or radiation of axillary nodes

• For International Breast Cancer Study Groups (IBCSG) centers, patients must have completed baseline Quality of Life (QL) Forms prior to randomization; the only exceptions are cognitive or physical impairment that interferes with QL assessment or inability to read any of the languages available on IBCSG QL forms; for non-IBCSG centers, extent of participation in the QL study is to be determined at the activation of the trial for each cooperative group

• Written informed consent must be signed and dated by the patient and the investigator prior to randomization

• Patients must be accessible for follow-up

• Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines

Exclusion Criteria:

• Patients who are postmenopausal (i.e., do not have an estradiol [E2] level in the premenopausal range) after surgery or after chemotherapy, whichever is later

• Patients with distant metastatic disease

• Patients with locally advanced inoperable breast cancer including inflammatory breast cancer or supraclavicular node involvement or with enlarged internal mammary nodes (unless pathologically negative) are not eligible; patients with involved internal mammary nodes detected by sentinel node biopsy that are not enlarged are eligible

• Patients with positive final margins (referring to only DCIS and invasive cancer, not lobular breast carcinoma in situ [LCIS]), except as noted; DCIS at a margin is permitted if a complete mastectomy has been performed

• Patients with clinically detectable residual axillary disease

• Patients with a history of prior ipsilateral or contralateral invasive breast cancer; patients with synchronous bilateral invasive breast cancer (diagnosed histologically within 2 months) are eligible if the bilateral disease meets all other eligibility criteria

• Patients with previous or concomitant invasive malignancy are not eligible; the exceptions are patients with the following (and only the following) malignancies (previous or concomitant) who are eligible if adequately treated:

• Basal or squamous cell carcinoma of the skin

• In situ non-breast carcinoma without invasion

• Contra- or ipsilateral in situ breast carcinoma

• Non-breast invasive malignancy diagnosed at least 5 years ago and without recurrence:

• Stage I papillary thyroid cancer

• Stage Ia carcinoma of the cervix

• Stage Ia or b endometrioid endometrial cancer

• Borderline or stage I ovarian cancer

• Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung, etc.) that would prevent prolonged follow-up; patients with previous thrombosis (e.g., deep vein thrombosis [DVT]) and/or embolism can be included only if medically suitable

• Patients who have had a bilateral oophorectomy or ovarian irradiation; patients who will be recommended to undergo oophorectomy within 5 years (e.g., breast cancer susceptibility gene [BRCA]1/2 gene carriers) and therefore for whom randomization to a treatment arm without OFS is inappropriate

• Patients with a history of noncompliance to medical regimens and patients who are considered potentially unreliable

• Patients who are pregnant or lactating at the time of randomization or who desire a pregnancy within 5 years; patients planning to use additional hormonal therapy apart from the randomized treatment during the next five years including all types of hormonal contraception; a pregnancy test is recommended for women of child-bearing potential who are sexually active and not using reliable contraceptive methods

• Patients who received endocrine therapy (including neoadjuvant and adjuvant) for more than 8 months after their breast cancer diagnosis; patients who are receiving endocrine therapy at randomization (and have received it for less than 8 months) may continue such therapy until protocol-specified tamoxifen/exemestane is initiated

• Patients who were taking tamoxifen or other selective estrogen receptor modulator (SERM) (e.g. Raloxifene) or hormone replacement therapy (HRT) within one year prior to their breast cancer diagnosis; prior oral contraceptives are allowed

• Patients who have received GnRH analogues as part of their breast cancer treatment prior to randomization

• Patients with psychiatric, addictive, or any disorder that would prevent compliance with protocol requirements

Related Conditions & MeSH terms

• Breast Neoplasms
• Estrogen Receptor Positive Breast Cancer
• Progesterone Receptor Positive Tumor
• Recurrent Breast Carcinoma
• Stage IA Breast Cancer
• Stage IB Breast Cancer
• Stage IIA Breast Cancer
• Stage IIB Breast Cancer
• Stage IIIA Breast Cancer

Intervention

Drug:
• Exemestane
Exemestane 25mg orally daily for 5 years plus ovarian function suppression

Other:
• Laboratory Biomarker Analysis
Correlative studies

Procedure:
• Oophorectomy
Undergo bilateral surgical oophorectomy

Other:
• Quality-of-Life Assessment
Ancillary studies

Radiation:
• Radiation Therapy
Undergo ovarian irradiation

Drug:
• Tamoxifen
Tamoxifen 20mg orally daily for 5 years
• Triptorelin
3.75 mg by im injection q28 days for 5 years

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CSSS Champlain-Charles Le Moyne	Greenfield Park	Quebec
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	BCCA-Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM-Hotel Dieu du Montreal	Montreal	Quebec
Canada	Hopital Du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Canada	Penticton Regional Hospital	Penticton	British Columbia
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Health Sciences North	Sudbury	Ontario
Canada	BCCA-Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Switzerland	International Breast Cancer Study Group	Bern
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Hematology Oncology Associates	Albuquerque	New Mexico
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Memorial Hospital of Arkansas City	Arkansas City	Kansas
United States	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina
United States	Mission Hospital-Memorial Campus	Asheville	North Carolina
United States	Atlanta Regional CCOP	Atlanta	Georgia
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Augusta Oncology Associates PC-Saint Sebastian	Augusta	Georgia
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Well Star Cobb Hospital	Austell	Georgia
United States	Harbor Hospital Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Bend Memorial Clinic	Bend	Oregon
United States	Saint Charles Medical Center-Bend	Bend	Oregon
United States	Southwestern Vermont Medical Center	Bennington	Vermont
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Suburban Hospital	Bethesda	Maryland
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Cancer Research Network Inc	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Faulkner Hospital	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	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Brookdale Hospital Medical Center	Brooklyn	New York
United States	Kings County Hospital	Brooklyn	New York
United States	State University of New York Downstate Medical Center	Brooklyn	New York
United States	University Hospital of Brooklyn	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Mills - Peninsula Hospitals	Burlingame	California
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
United States	Graham Hospital Association	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
United States	Saint Luke's Hospital	Cedar Rapids	Iowa
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Erlanger Medical Center	Chattanooga	Tennessee
United States	Memorial Hospital	Chattanooga	Tennessee
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Weiss Memorial Hospital	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Memorial Hospital Colorado Springs	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Carolinas HealthCare System NorthEast	Concord	North Carolina
United States	Emerson Hospital/MGH Cancer Center	Concord	Massachusetts
United States	John Muir Medical Center-Concord Campus	Concord	California
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Clements University Hospital	Dallas	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Zale Lipshy University Hospital	Dallas	Texas
United States	Mass General/North Shore Cancer Center	Danvers	Massachusetts
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Dekalb Medical Center	Decatur	Georgia
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Colorado Cancer Research Program NCORP	Denver	Colorado
United States	Denver Health Medical Center	Denver	Colorado
United States	Denver Veterans Administration Medical Center	Denver	Colorado
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	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	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Bayhealth Medical Center at Kent General	Dover	Delaware
United States	Finley Hospital	Dubuque	Iowa
United States	Medical Associates Clinic PC	Dubuque	Iowa
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Midelfort Clinic-Clairemont Campus	Eau Claire	Wisconsin
United States	Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	The Shaw Regional Cancer Center	Edwards	Colorado
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Aurora Cancer Care-Southern Lakes	Elkhorn	Wisconsin
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Exeter Hospital	Exeter	New Hampshire
United States	Kaiser Permanente - Fair Oaks Medical Center	Fairfax	Virginia
United States	Saint Francis Hospital	Federal Way	Washington
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	MetroWest Medical Center-Framingham Union Hospital	Framingham	Massachusetts
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Unity Hospital	Fridley	Minnesota
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Jones Clinic	Germantown	Tennessee
United States	Glendale Memorial Hospital and Health Center	Glendale	California
United States	Adirondack Cancer Center	Glens Falls	New York
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Altru Hospital	Grand Forks	North Dakota
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Benefis Healthcare-West Campus	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Marin General Hospital	Greenbrae	California
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	The Cancer Institute of New Jersey Hamilton	Hamilton	New Jersey
United States	Hartford Hospital	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Penn State Hershey Cancer Institute-Clinical Trials Office	Hershey	Pennsylvania
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Community Hospital East	Indianapolis	Indiana
United States	Community Regional Cancer Care-North	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Allegiance Health	Jackson	Michigan
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Jupiter Medical Center	Jupiter	Florida
United States	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire
United States	Keesler Medical Center	Keesler Air Force Base	Mississippi
United States	Kettering Medical Center	Kettering	Ohio
United States	Kewanee Hospital	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Scripps Cancer Center	La Jolla	California
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Horizon Oncology Center	Lafayette	Indiana
United States	IU Health Arnett Cancer Care	Lafayette	Indiana
United States	Northwell Health NCORP	Lake Success	New York
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania
United States	Doctor's Hospital of Laredo	Laredo	Texas
United States	Kaiser Permanente - Largo Medical Center	Largo	Maryland
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Lima Memorial Hospital	Lima	Ohio
United States	Meeker County Memorial Hospital	Litchfield	Minnesota
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Longmont United Hospital	Longmont	Colorado
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	Kaiser Permanente - Towson Medical Center	Lutherville	Maryland
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	UW Health Oncology-One South Park	Madison	Wisconsin
United States	Elliot Hospital	Manchester	New Hampshire
United States	North Shore University Hospital	Manhasset	New York
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Vince Lombardi Cancer Clinic-Marinette	Marinette	Wisconsin
United States	Marquette General Hospital	Marquette	Michigan
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Mid-Michigan Medical Center - Midland	Midland	Michigan
United States	Medical Consultants Limited	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Saint Joseph Regional Medical Center - Mishawaka	Mishawaka	Indiana
United States	Memorial Medical Center	Modesto	California
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	Morristown Medical Center	Morristown	New Jersey
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Meharry Medical College	Nashville	Tennessee
United States	Nashville Oncology Associates PC	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	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Saint Vincent's Hospital and Medical Center of New York	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Newton-Wellesley Hospital	Newton	Massachusetts
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Sutter Cancer Research Consortium	Novato	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Providence - Saint Peter Hospital	Olympia	Washington
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute	Palo Alto	California
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Aria Health-Torresdale Campus	Philadelphia	Pennsylvania
United States	Chestnut Hill Health System	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	FirstHealth of the Carolinas-Moore Regional Hosiptal	Pinehurst	North Carolina
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Kaiser Permanente	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Mercy Hospital	Portland	Maine
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Western Oncology Research Consortium	Portland	Oregon
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Mercy Regional Cancer Center	Redding	California
United States	Kaiser Permanente-Redwood City	Redwood City	California
United States	Renown Regional Medical Center	Reno	Nevada
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Frisbie Hospital	Rochester	New Hampshire
United States	Mayo Clinic	Rochester	Minnesota
United States	OSF Saint Anthony Medical Center	Rockford	Illinois
United States	Kaiser Permanente - Shady Grove Medical Center	Rockville	Maryland
United States	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia
United States	Kaiser Permanente-Roseville	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Sarah Culbertson Memorial Hospital	Rushville	Illinois
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Mercy General Hospital	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Lakeland Hospital	Saint Joseph	Michigan
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Anthony's Medical Center	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	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salinas Valley Memorial	Salinas	California
United States	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	University of California San Diego	San Diego	California
United States	Veterans Administration-San Diego Medical Center	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	San Francisco General Hospital	San Francisco	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Rafael	San Rafael	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Santa Rosa Memorial Hospital	Santa Rosa	California
United States	Florida Cancer Specialists - Sarasota Downtown	Sarasota	Florida
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial University Medical Center	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Scranton Hematology Oncology	Scranton	Pennsylvania
United States	Nanticoke Memorial Hospital	Seaford	Delaware
United States	Group Health Cooperative of Puget Sound Oncology Consortium	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Grand View Hospital	Sellersville	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota
United States	Medical X-Ray Center	Sioux Falls	South Dakota
United States	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	South Shore Hospital	South Weymouth	Massachusetts
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Staten Island University Hospital	Staten Island	New York
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Flower Hospital	Sylvania	Ohio
United States	MultiCare Allenmore Hospital	Tacoma	Washington
United States	Multicare Health System	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Scott and White Memorial Hospital	Temple	Texas
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Saint Anne Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas
United States	Charlotte Hungerford Hospital Center for Cancer Care	Torrington	Connecticut
United States	Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Main Office	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
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	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota
United States	Woodwinds Health Campus	Woodbury	Minnesota
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Greene Memorial Hospital	Xenia	Ohio
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	Tod Children's Hospital - Forum Health	Youngstown	Ohio
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (8)

Lead Sponsor	Collaborator
ETOP IBCSG Partners Foundation	Breast International Group, Cancer and Leukemia Group B, National Cancer Institute (NCI), NCIC Clinical Trials Group, North Central Cancer Treatment Group, NSABP Foundation Inc, SWOG Cancer Research Network

Countries where clinical trial is conducted

United States,  Canada,  Switzerland, 

References & Publications (2)

Francis PA, Fleming GF, Lang I, Ciruelos EM, Bonnefoi HR, Bellet M, Bernardo A, Climent MA, Martino S, Bermejo B, Burstein HJ, Davidson NE, Geyer CE Jr, Walley BA, Ingle JN, Coleman RE, Muller B, Le Du F, Loibl S, Winer EP, Ruepp B, Loi S, Colleoni M, Coa — View Citation

Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival	Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow-up.	5-year estimates, reported at a median follow-up of 67 months.
Secondary	Breast Cancer-free Interval	Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer-free interval is defined as the time from randomization to invasive breast cancer recurrence at local, regional, or distant site, or invasive contralateral breast cancer; or censored at date of last follow up.	5-year estimates, reported at a median follow-up of 67 months.
Secondary	Distant Recurrence-free Interval	Estimated percentage of patients alive and disease-free at 5 years from randomization, where distant recurrence-free Interval is defined as the time from randomization to invasive breast cancer recurrence at distant site, or invasive contralateral breast cancer; or censored at date of last follow up.	5-year estimates, reported at a median follow-up of 67 months.
Secondary	Overall Survival	Estimated percentage of patients alive at 8 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.	8-year estimates, reported at a median follow-up of 8 years