Early Surgery or Standard Palliative Therapy in Treating Patients With Stage IV Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Randomized Phase III Trial of the Value of Early Local Therapy for the Intact Primary Tumor in Patients With Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01242800
• Other study ID #: E2108
• Secondary ID: ECOG-E2108U10CA1
• Status: Completed
• Phase: N/A
• Start date: May 16, 2011
• Est. completion date: December 21, 2022

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: The primary tumor might be a source of re-seeding of distant sites and therefore elimination of this source of metastasizing cells by early local therapy may be of benefit.

PURPOSE: This randomized phase III trial is studying early surgery to see how well it works compared to standard palliative therapy in treating patients with stage IV breast cancer.

Description:

OBJECTIVES:

Primary

• To evaluate whether early local therapy of intact primary disease in patients with Stage IV breast cancer whose disease does not progress during initial optimal systemic therapy, will result in prolonged survival, compared to patients who receive local therapy for palliation only.

Secondary

• To compare the time to uncontrolled chest wall disease between patients who receive early local therapy versus patients who receive palliative local therapy.

• To determine whether there is a difference in health-related quality-of-life (HRQOL) between patients who receive early local therapy versus patients who receive palliative local therapy.

• To determine whether the absolute value of circulating tumor cells (CTC) burden at 6 months following randomization (time +6) will be lower in the palliative therapy arm than in early local therapy arm, and whether this value is inversely related to survival (lower CTC, longer survival).

Exploratory

• To collect tumor and blood specimens for future exploration of the biological interactions between the primary tumor and metastatic lesions and the effect of primary tumor resection.

OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor and treatment plan (ER+ or PR+, HER2-, endocrine therapy alone vs ER+ or PR+, and HER2-, chemotherapy and/or endocrine therapy vs ER- or PR-, and HER2- vs HER2+), and number of involved organ systems with distant disease (regional nodes in the axillary, supraclavicular, and internal mammary locations are not considered distant sites) (1 vs > 1). Patients are randomized to 1 of 2 treatment arms in 1:1 ratio.

• Arm I: Patients receive standard palliative therapy, if needed, to address symptoms such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a combination of both.

• Arm II: Patients undergo surgery comprising breast-conserving therapy (BCT) or total mastectomy according to patient and treating physician preference. Surgery is to occur no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical margins must be achieved with re-excision or mastectomy for patients undergoing BCT. After completion of BCT, patients undergo radiotherapy once a day, 5 days per week. Patients who had mastectomy undergo radiotherapy at the discretion of treating physician.

Patients may undergo blood and tumor tissue sample collection for circulating tumor cells (CTC) burden and future studies.

Patients complete the Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT- TOI) and FACT - General (22) and the Breast Cancer Subscale (FACT-B) quality-of-life questionnaires at baseline and periodically during study.

After completion of study therapy, patients are followed up periodically for 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: December 21, 2022
• Est. primary completion date: December 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

Inclusion Criteria:

• Diagnosis of intact primary (not recurrent) invasive carcinoma of the breast

• Stage IV disease

• Confirmation of the primary tumor should be by needle biopsy (preferred)

• Incisional surgical biopsy allowed as long as there is residual palpable or tumor image in the breast

• Patients must be judged to be candidates for complete resection with free margins followed by radiation therapy (if radiation therapy is indicated)

• For women not undergoing axillary dissection, sentinel node biopsy should document an axillary nodal burden of 1-2 involved lymph nodes (i.e., ACOSOG Z-11 criteria may be applied)

• Prior non-invasive (Ductal Carcinoma In Situ) cancer allowed provided there has been no recurrence

• Prior ipsilateral invasive cancer allowed if more than 5 years previous

• Patients should have at least one organ system involved with distant metastatic disease

• If patient has only one metastatic lesion/focus, this must be proven by biopsy and the pathology report confirming the diagnosis of primary breast cancer, as well as the metastatic site, must be available

• Must have available radiologic reports documenting disease status within the past 6 weeks prior to initiating systemic therapy

• CNS metastases allowed provided projected survival > 6 months

• Patients must have completed at least 16 weeks of optimal systemic therapy (appropriate to the tumor biological profile and the patient's age and menopausal status)

• If systemic therapy is discontinued for toxicity, but there is no distant progression and at least 12 weeks of therapy have been delivered, then the patient remains eligible

• Radiation therapy (if indicated) must begin within 12 weeks of final therapeutic surgical procedure (including re-excision for free margins and completion of axillary dissection)

• Patients may register at any time from the time of diagnosis of stage IV breast cancer (if eligibility criteria met) to the time when a maximum of 30 weeks of induction systemic therapy has been completed

• Patients must be randomized within 16-32 weeks after the start of systemic therapy

• Patients must not have experienced disease progression since the start of systemic therapy, as evidenced by radiographic documentation of disease status before treatment and within 4 weeks +/- 2 weeks prior to randomization, including:

• No new sites of disease

• No enlargement of existing sites by 20% or more in longest diameter

• No symptomatic deterioration

• Patients who require radiotherapy to bone metastases during induction systemic therapy are eligible

• Local disease at the primary site must be asymptomatic

• Hormone receptor status known

• Menopausal status not specified

• Patients must have adequate organ function to undergo local therapy 4 weeks +/- 2 weeks prior to randomization per investigator discretion and institutional guidelines

• More than 5 years since other primary cancers that were curatively treated

• Negative pregnancy test

• Fertile patients must use an accepted and effective contraception method

Exclusion criteria:

• Synchronous contralateral breast cancer

• Pregnant or nursing

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Stage IV Breast Cancer

Intervention

Procedure:
• palliative surgery
Undergo standard palliative surgery
• therapeutic conventional surgery
Undergo early surgery

Radiation:
• palliative radiation therapy
Undergo standard palliative radiotherapy
• radiation therapy
Undergo radiotherapy

Locations

Country	Name	City	State
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Saudi Arabia	King Faisal Specialist Hospital and Research Center	Riyadh
South Africa	Pretoria Academic Hospital	Pretoria
United States	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii
United States	Leeward Radiation Oncology	'Ewa Beach	Hawaii
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Lovelace Medical Center - Downtown	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	McFarland Clinic, PC	Ames	Iowa
United States	Providence Cancer Center	Anchorage	Alaska
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland
United States	Langlade Memorial Hospital	Antigo	Wisconsin
United States	Fox Valley Hematology and Oncology - East Grant Street	Appleton	Wisconsin
United States	Fox Valley Surgical Associates at Appleton Medical Center	Appleton	Wisconsin
United States	Theda Care Cancer Institute	Appleton	Wisconsin
United States	Emory Crawford Long Hospital	Atlanta	Georgia
United States	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Harrison Medical Center	Bremerton	Washington
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Memorial Hospital	Carthage	Illinois
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	Resurrection Medical Center	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Enloe Cancer Center at Enloe Medical Center	Chico	California
United States	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Batte Cancer Center at Northeast Medical Center	Concord	North Carolina
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital	Cooperstown	New York
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Herbert D. Kerman Regional Oncology Center - Daytona Beach	Daytona Beach	Florida
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Easton Regional Cancer Center at Easton Hospital	Easton	Pennsylvania
United States	Shore Regional Cancer Center at Memorial Hospital - Easton	Easton	Maryland
United States	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin
United States	St. Elizabeth Medical Center	Edgewood	Kentucky
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Eureka Community Hospital	Eureka	Illinois
United States	North Bay Cancer Center	Fairfield	California
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	Center for Cancer Care at Goshen General Hospital	Goshen	Indiana
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	California Cancer Care, Incorporated - Greenbrae	Greenbrae	California
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Hawaii Medical Center - East	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	St. Mary's Regional Cancer Center at St. Mary's Medical Center	Huntington	West Virginia
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	William N. Wishard Memorial Hospital	Indianapolis	Indiana
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Baylor Medical Center at Irving	Irving	Texas
United States	Foote Memorial Hospital	Jackson	Michigan
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	West Tennessee Cancer Center at Jackson-Madison County General Hospital	Jackson	Tennessee
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	St. Mary Regional Cancer Center	Langhorne	Pennsylvania
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Doctor's Hospital of Laredo	Laredo	Texas
United States	University of New Mexico Cancer Center - South	Las Cruces	New Mexico
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Todd Cancer Institute at Long Beach Memorial Medical Center	Long Beach	California
United States	McDonough District Hospital	Macomb	Illinois
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Norris Cotton Cancer Center at Catholic Medical Center	Manchester	New Hampshire
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	Immanuel St. Joseph's	Mankato	Minnesota
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Vince Lombardi Cancer Clinic - Marinette	Marinette	Wisconsin
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas, PA - McPherson	McPherson	Kansas
United States	Charles A. & Betty Bott Cancer Center at Holy Redeemer Hospital	Meadowbrook	Pennsylvania
United States	Mountain States Tumor Institute - Meridian	Meridian	Idaho
United States	MidMichigan Medical Center - Midland	Midland	Michigan
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Trinity CancerCare Center	Minot	North Dakota
United States	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center	Mishawaka	Indiana
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Community Hospital of the Monterey Peninsula Comprehensive Cancer Center	Monterey	California
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	El Camino Hospital Cancer Center	Mountain View	California
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Saint Luke's Mountain States Tumor Institute	Nampa	Idaho
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Beth Israel Medical Center - Petrie Division	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Lakeside Hospital	Omaha	Nebraska
United States	St. Joseph Hospital Regional Cancer Center - Orange	Orange	California
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Southern Ohio Medical Center Cancer Center	Portsmouth	Ohio
United States	Dyson Center for Cancer Care at Vassar Brothers Medical Center	Poughkeepsie	New York
United States	CCOP - Kansas City	Prairie Village	Kansas
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Mercy Clinic Cancer and Hematology - Rolla	Rolla	Missouri
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan
United States	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	St. Anthony's Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Doctors Medical Center - San Pablo Campus	San Pablo	California
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Radiation Oncology Center at Kennedy Health System - Sewell	Sewell	New Jersey
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Stanford Cancer Center	Stanford	California
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Aurora Medical Center	Summit	Wisconsin
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	J. Phillip Citta Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Mountain States Tumor Institute at St. Luke's	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic - Two Rivers	Two Rivers	Wisconsin
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. Mary Regional Cancer Center at St. Mary Medical Center	Walla Walla	Washington
United States	St. John Macomb Hospital	Warren	Michigan
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Marshfield Clinic - Wausau Center	Wausau	Wisconsin
United States	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Oncology Alliance, SC - Milwaukee - West	Wauwatosa	Wisconsin
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Dickstein Cancer Treatment Center at White Plains Hospital Center	White Plains	New York
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Susquehanna Cancer Center at Divine Providence Hospital	Williamsport	Pennsylvania
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Riverview UW Cancer Center at Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Saudi Arabia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-year Overall Survival Rate	Overall survival (OS) was defined as time from randomization to death from any cause. All patients will be followed for survival through 5 years. Cases with incomplete follow-up or without record of vital status will be censored at the date of last contact. 3-year OS rate was estimated using Kaplan-Meier method.	Assessed at baseline, then every 3 months within 2 years and every 6 months between 2-5 years, up to 5 years
Secondary	3-year Cumulative Incidence of Locoregional Recurrence/Progression	For patients in arm II (early local therapy), time to locoregional recurrence was defined as time from randomization to date of locoregional recurrence; for patients in arm A (continued systemic therapy), time to locoregional progression was defined as time from randomization to date of locoregional progression. In this study, locoregional recurrence was defined as the new development or clinically significant increase in size of any supraclavicular, infraclavicular, internal mammary or axillary adenopathy or chest wall disease or invasive in-breast recurrence for patients on arm B; for patients on arm A, locoregional progression was defined as the development of symptoms leading to a decision for local therapy. Locoregional recurrence/progression and distant progression were followed separately in the study, and the occurrence of one did not preclude the other getting reported. 3-year cumulative incidence of locoregional recurrence/progression was estimated.	Assessed at baseline, then every 3 months within 2 years and every 6 months between 2-5 years, up to 5 years
Secondary	Health-related Quality of Life (HRQL)	The Functional Assessment of Cancer Therapy-Breast Trial Outcome Index (FACT-B TOI) was used as the primary HRQL endpoint, measured by the prorated aggregate score of the 24 items from the FACT-B (7 functional well-being, 7 physical well-being, 10 breast cancer specific items). The theoretical range of the prorated aggregate score was 0-96, higher scores indicate better quality of life.	Assessed at 18 months after randomization