Chemotherapy With or Without Bevacizumab in Treating Women With Stage I, Stage II, or Stage IIIA Breast Cancer That Can Be Removed By Surgery

Study ID	NCT00408408
Status	Recruiting
Phase	3
Source	ClinicalTrials.gov

Started	Nov 1 2006
Last Updated	Feb 2 2010
Estimated Completion	Feb 2 2010

About this clinical study

Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy and bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known which chemotherapy regimen is more effective with or without bevacizumab in treating breast cancer.

PURPOSE: This randomized phase III trial is studying six different chemotherapy regimens to compare how well they work with or without bevacizumab in treating women with stage I, stage II, or stage IIIA breast cancer that can be removed by surgery.

Condition / Disease

Breast Cancer

Therapy

bevacizumab
capecitabine
cyclophosphamide
docetaxel
doxorubicin hydrochloride
gemcitabine hydrochloride
conventional surgery

Study Outcomes

Pathologic complete response (pCR) of the primary tumor in the breast
pCR in the breast and nodes
Clinical overall response (cOR) following docetaxel alone, docetaxel/capecitabine, and docetaxel/gemcitabine hydrochloride, with or without bevacizumab, as assessed by physical exam at the completion of the docetaxel-based portion of chemotherapy
cOR as assessed by physical exam at the completion of the sequential chemotherapy regimens
Clinical complete response (cCR) following docetaxel alone, docetaxel/capecitabine, and docetaxel/gemcitabine hydrochloride, with or without bevacizumab, as assessed by physical exam at completion of therapy
cCR as assessed by physical exam at the completion of the sequential chemotherapy regimens
Percentage of cardiac events
Percentage of surgical complications
Toxicities
Disease-free survival
Incidence of recurrence after mastectomy
Incidence of local recurrence in the ipsilateral breast following lumpectomy
Incidence of regional recurrence
Incidence of distant recurrence
Incidence of contralateral breast cancer
Incidence of second primary cancer
Mortality from any cause prior to recurrence or second primary cancer

Description

OBJECTIVES:

Primary

Compare the efficacy of docetaxel followed by doxorubicin hydrocloride and cyclophosphamide (AC) vs docetaxel and capecitabine followed by AC vs docetaxel and gemcitabine hydrochloride followed by AC, with or without bevacizumab, in terms of an increase in the rate of pathologic complete response (pCR) in the breast, in women with palpable or operable breast cancer.

Secondary

Compare docetaxel/capecitabine with AC vs docetaxel/gemcitabine hydrochloride with AC vs docetaxel with AC, with or without bevacizumab, in terms of the rate of pCR in the breast and all post-therapy lymph nodes evaluated histologically (pCR breast and nodes).

Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens (docetaxel with AC, docetaxel and capecitabine with AC, and docetaxel and gemcitabine hydrochloride with AC) will increase the rate of pCR of the breast and nodes compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients.

Determine whether the addition of capecitabine or gemcitabine hydrochloride to docetaxel, with or without bevacizumab, will increase the rate of clinical overall response (cOR) compared to docetaxel alone with or without bevacizumab in these patients.

Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens will increase the rate of cOR compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients.

Determine whether the addition of capecitabine or gemcitabine hydrochloride to docetaxel, with or without bevacizumab, will increase the rate of clinical complete response (cCR) compared to docetaxel alone with or without bevacizumab in these patients.

Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens (docetaxel with AC, docetaxel/capecitabine with AC, and docetaxel/gemcitabine hydrochloride with AC) will increase the rate of cCR compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients.

Identify gene expression profiles that can predict pCR in patients treated with the different sequential docetaxel/anthracycline-based regimens with or without bevacizumab.

Identify gene expression profiles that can predict cOR in patients treated with docetaxel alone, docetaxel/capecitabine, or docetaxel/gemcitabine hydrochloride with or without bevacizumab.

Determine the accuracy of an in vitro chemoresponse assay (ChemoFx��) as a predictor of pCR in patients treated with the different sequential docetaxel/anthracycline-based regimens without bevacizumab.

Determine the accuracy of ChemoFx�� as a predictor of cOR in patients treated with docetaxel alone, docetaxel/capecitabine, or docetaxel/gemcitabine hydrochloride without bevacizumab in these patients.

Determine the impact of preoperative bevacizumab and sequential chemotherapy regimens and postoperative bevacizumab therapy on cardiac function in these patients.

Determine the impact of bevacizumab on surgical complications in these patients.

Determine the toxicity of the preoperative regimens and the toxicity of postoperative bevacizumab in these patients.

Compare the docetaxel/anthracycline-based regimens with vs without bevacizumab, in terms of an increase in disease-free survival, of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor size (2-4 cm vs > 4 cm), nodal status (negative vs positive), hormone receptor status (estrogen receptor [ER]-positive and/or progesterone-receptor [PgR]-positive vs ER- and PgR-negative), and age (< 50 years vs �� 50 years). Patients are randomized to 1 of 6 treatment arms.

Arm I: Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive AC comprising doxorubicin hydrochloride IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses. Patients then undergo surgery (lumpectomy or mastectomy).

Arm II: Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel as in Arm I. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive AC as in Arm I and 2 additional courses of bevacizumab concurrent with the first 2 courses of AC. Patients then undergo surgery as in Arm I. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Arm III: Patients receive docetaxel as in Arm I and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive AC as in Arm I. Patients then undergo surgery as in Arm I.

Arm IV: Patients receive bevacizumab as in Arm II and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive bevacizumab IV over 30 minutes on day 1 and AC as in Arm I. Treatment repeats every 3 weeks for up to 4 courses (2 courses of bevacizumab). Patients then undergo surgery as in Arm I. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm II.

Arm V: Patients receive docetaxel as in Arm I and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive AC as in Arm I. Patients then undergo surgery as in Arm I.

Arm VI: Patients receive docetaxel as in Arm I, gemcitabine hydrochloride as in Arm V, and bevacizumab as in Arm II. Patients then receive AC with bevacizumab as in Arm II. Patients then undergo surgery as in Arm I. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm II.

Core needle biopsies are performed at baseline. Tumor tissue samples are also collected during definitive surgery. Samples are examined for gene expression and polymorphism by reverse transcriptase-polymerase chain reaction analysis and chemoresponse assay (ChemoFx��).

After completion of study therapy, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 1,200 patients will be accrued for this study.

Overview

Gender	female

Target Enrollment	1200

Recruiting Healthy Volunteers	No

Locations

Newark Beth Israel Medical Center	Newark	NJ
Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	NY
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	NJ
Cancer Institute of New Jersey at Hamilton	Hamilton Square	NJ
Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	NJ
Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	NY
Saint Francis Hospital Cancer Center	Poughkeepsie	NY
Batte Cancer Center at Northeast Medical Center	Concord	NC
Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	NC
Annie Penn Cancer Center	Reidsville	NC
Alamance Cancer Center at Alamance Regional Medical Center	Burlington	NC
Tucker Center for Cancer Care at Orange Regional Medical Center	Middletown	NY
Seacoast Cancer Center at Wentworth - Douglass Hospital	Dover	NH
Immanuel Medical Center
St. James Healthcare Cancer Care	Butte	MT
St. Peter's Hospital	Helena	MT
Sletten Cancer Institute at Benefis Healthcare	Great Falls	MT
Northern Rockies Radiation Oncology Center	Billings	MT
Montana Cancer Specialists at Montana Cancer Center	Missoula	MT
St. Vincent Healthcare Cancer Care Services	Billings	MT
Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	NE
Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	NE
Creighton University Medical Center	Omaha	NE
CCOP - Missouri Valley Cancer Consortium	Omaha	NE
Cancer Resource Center - Lincoln	Lincoln	NE
Forsyth Regional Cancer Center at Forsyth Medical Center	Winston Salem	NC
Hope A Women's Cancer Center	Asheville	NC
Case Comprehensive Cancer Center	Cleveland	OH
CCOP - Dayton	Dayton	OH
Cancer Treatment Center	Wooster	OH
Cancer Care Center, Incorporated	Salem	OH
Blanchard Valley Medical Associates	Findlay	OH
CCOP - Toledo Community Hospital	Toledo	OH
Charles F. Kettering Memorial Hospital	Dayton	OH
Fulton County Health Center	Wauseon	OH
Good Samaritan Hospital
Flower Hospital Cancer Center	Sylvania	OH
David L. Rike Cancer Center at Miami Valley Hospital	Dayton	OH
Clinton Memorial Hospital	Wilmington	OH
Barberton Citizens Hospital	Barberton	OH
Aultman Cancer Center at Aultman Hospital	Canton	OH
Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	NC
Randolph Hospital	Asheboro	NC
Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	NC
Marion L. Shepard Cancer Center at Beaufort County Hospital	Washington	NC
Iredell Memorial Hospital	Statesville	NC
Rutherford Hospital	Rutherfordton	NC
Southeastern Medical Oncology Center - Goldsboro	Goldsboro	NC
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
Altru Cancer Center at Altru Hospital	Grand Forks	ND
Wayne Memorial Hospital, Incorporated	Goldsboro	NC
Wake Forest University Comprehensive Cancer Center	Winston Salem	NC
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	MT
Kalispell Regional Medical Center	Kalispell	MT
Miller - Dwan Medical Center	Duluth	MN
Minnesota Oncology Hematology, PA - Maplewood	Maplewood	MN
Mercy and Unity Cancer Center at Unity Hospital	Minneapolis	MN
Mercy and Unity Cancer Center at Mercy Hospital	Minneapolis	MN
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Minneapolis	MN
Minnesota Oncology Hematology, PA - Woodbury	Saint Paul	MN
Park Nicollet Cancer Center	Saint Louis Park	MN
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	MN
Hattiesburg Clinic, PA at Forrest General	Hattiesburg	MS
United Hospital	St. Paul	MN
St. Francis Cancer Center at St. Francis Medical Center	Shakopee	MN
Ridgeview Medical Center	Waconia	MN
Hennepin County Medical Center - Minneapolis	Minneapolis	MN
Fairview Southdale Hospital
St. Joseph Mercy Oakland	Pontiac	MI
St. Mary Mercy Hospital	Livonia	MI
St. John Macomb Hospital	Warren	MI
Sparrow Regional Cancer Center	Lansing	MI
Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	MI
Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe	MI
West Michigan Cancer Center	Kalamazoo	MI
Fairview Ridges Hospital	Burnsville	MN
Duluth Clinic Cancer Center - Duluth	Duluth	MN
CCOP - Metro-Minnesota	Minneapolis	MN
CCOP - Duluth	Duluth	MN
CCOP - Cancer Research for the Ozarks	Springfield	MO
CCOP - Kansas City	Kansas City	MO
Billings Clinic - Downtown	Billings	MT
Bozeman Deaconess Cancer Center	Bozeman	MT
Big Sky Oncology	Great Falls	Mt
Truman Medical Center - Hospital Hill	Kansas City	MO
St. John's Regional Medical Center
CCOP - Montana Cancer Consortium	Billings	MT
Community Medical Center
Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	MT
Kalispell Medical Oncology at KRMC	Kalispell	MT
Guardian Oncology and Center for Wellness	Missoula	MT
Great Falls Clinic - Main Facility	Great Falls	MT
Glacier Oncology, PLLC	Kalispell	MT
St. John's Regional Health Center
Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	MO
Heartland Regional Medical Center	St Joseph	MO
Hulston Cancer Center at Cox Medical Center South	Springfield	MO
Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	MO
David C. Pratt Cancer Center at St. John's Mercy	St Louis	MO
CCOP - St. Louis-Cape Girardeau	Saint Louis	MO
Liberty Hospital	Liberty	MO
Midwest Hematology Oncology Group, Incorporated	Saint Louis	MO
Saint Louis University Cancer Center	Saint Louis	MO
Saint Francis Medical Center	Cape Girardeau	MO
Research Medical Center
Parvin Radiation Oncology	Kansas City	MO
Grandview Hospital	Dayton	OH
Hematology Oncology Center	Elyria	OH
Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	WA
Good Samaritan Cancer Center	Puyallup	WA
CCOP - Northwest	Tacoma	WA
Auburn Regional Center for Cancer Care	Auburn	WA
Allenmore Hospital	Tacoma	WA
MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	WA
Providence Centralia Hospital	Centralia	WA
Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	WV
Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	WV
St. Francis Hospital	Evanston	IL
St. Clare Hospital	Lakewood	WA
Providence St. Peter Hospital Regional Cancer Center	Olympia	WA
Virginia Commonwealth University Massey Cancer Center	Richmond	VA
Fredericksburg Oncology, Incorporated	Fredericksburg	VA
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Salt Lake City	UT
LDS Hospital	Salt Lake City	UT
Huntsman Cancer Institute at University of Utah	Salt Lake City	UT
Dixie Regional Medical Center - East Campus	Saint George	UT
American Fork Hospital
Sandra L. Maxwell Cancer Center	Cedar City	UT
Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	UT
Mountainview Medical	Montpelier	VT
Fletcher Allen Health Care - University Health Center Campus	Burlington	VT
Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	UT
Utah Valley Regional Medical Center - Provo	Provo	UT
Schiffler Cancer Center at Wheeling Hospital	Wheeling	WV
West Virginia University Health Sciences Center - Charleston	Charleston	WV
Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	WY
CHUM - Hopital Saint-Luc	Montreal	Quebec
Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	WI
Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	WI
Saint Joseph's Hospital	Marshfield	WI
CHUM - Hotel Dieu Hospital	Montreal	Quebec
Hopital Notre-Dame du CHUM	Montreal	Quebec
St. Mary's Hospital Center	Montreal	Quebec
San Juan City Hospital	San Juan
Royal Victoria Hospital - Montreal	Montreal	Quebec
Montreal General Hospital	Montreal	Quebec
Jewish General Hospital - Montreal	Montreal	Quebec
Ministry Medical Group at Saint Mary's Hospital	Rhinelander	WI
Medical College of Wisconsin Cancer Center	Milwaukee	WI
Marshfield Clinic - Chippewa Center	Chippewa Falls	WI
Marshfield Clinic - Indianhead Center	Rice Lake	WI
Gundersen Lutheran Center for Cancer and Blood	La Crosse	WI
Aurora Women's Pavilion of West Allis Memorial Hospital	Milwaukee	WI
Aurora Sinai Medical Center	Milwaukee	WI
Marshfield Clinic - Lakeland Center	Minocqua	WI
Marshfield Clinic - Marshfield Center	Marshfield	WI
Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	WI
Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	WI
Marshfield Clinic - Weston Center	Weston	WI
Marshfield Clinic - Wausau Center	Wausau	WI
University of Texas Health Science Center at San Antonio	San Antonio	TX
Doctor's Hospital of Laredo	Laredo	TX
Toledo Clinic, Incorporated - Main Clinic	Toledo	OH
Toledo Hospital
Toledo Clinic - Oregon	Oregon	OH
Summa Center for Cancer Care at Akron City Hospital	Akron	OH
St. Vincent Mercy Medical Center	Toledo	OH
UVMC Cancer Care Center at Upper Valley Medical Center	Troy	OH
Wayne Hospital	Greenville	OH
Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	PA
Bryn Mawr Hospital	Bryn Mawr	PA
Kaiser Permanente Health Care - Portland	Portland	OR
Cleo Craig Cancer Research Clinic	Lawton	OK
Wood County Oncology Center	Bowling Green	OH
St. Luke's Hospital	Bethlehem	PA
St. Charles Mercy Hospital	Oregon	OH
Mercy Hospital of Tiffin	Tiffin	OH
Middletown Regional Hospital	Middletown	OH
Medical University of Ohio Cancer Center	Toledo	OH
McDowell Cancer Center at Akron General Medical Center	Akron	OH
Lima Memorial Hospital
North Coast Cancer Care - Clyde	Clyde	OH
North Coast Cancer Care, Incorporated	Sandusky	OH
St. Anne Mercy Hospital	Toledo	OH
Samaritan North Cancer Care Center	Dayton	OH
Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	OH
Northwest Ohio Oncology Center	Maumee	OH
Cancer Center of Paoli Memorial Hospital	Paoli	PA
CCOP - Main Line Health	Wynnewood	PA
Hollings Cancer Center at Medical University of South Carolina	Charleston	SC
Roper St. Francis Cancer Center at Roper Hospital	Charleston	SC
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	SC
CCOP - Upstate Carolina	Spartanburg	SC
CCOP - Greenville	Greenville	SC
Medical X-Ray Center, PC	Sioux Falls	SD
Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	SD
University of Tennessee Cancer Institute - Memphis	Germantown	TN
Thompson Cancer Survival Center	Knoxville	TN
Nashville Oncology Associates, PC	Nashville	TN
MBCCOP - Meharry Medical College - Nashville	Nashville	TN
AnMed Cancer Center	Anderson	SC
York Cancer Center at Apple Hill Medical Center	York	PA
Geisinger Medical Group - Scenery Park	State College	PA
Lankenau Cancer Center at Lankenau Hospital	Wynnewood	PA
Geisinger Cancer Institute at Geisinger Health	Danville	PA
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
Cherry Tree Cancer Center	Hanover	PA
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	PA
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	PA
UPMC Cancer Centers	Pittsburgh	PA
St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	PA
Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	PA
Mount Nittany Medical Center	State College	PA
Saint Joseph Mercy Cancer Center	Ann Arbor	MI
Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	MI
Aurora Presbyterian Hospital
Boulder Community Hospital
Valley Medical Oncology	Fremont	CA
Valley Medical Oncology Consultants - Pleasanton	Pleasanton	CA
Valley Medical Oncology Consultants - Castro Valley	Castro Valley	CA
CCOP - Colorado Cancer Research Program	Denver	CO
Exempla Lutheran Medical Center	Wheat Ridge	CO
North Colorado Medical Center	Greeley	CO
North Suburban Medical Center	Thornton	CO
Memorial Hospital Cancer Center - Colorado Springs	Colorado Springs	CO
McKee Medical Center	Loveland	CO
Hope Cancer Care Center at Longmont United Hospital	Longmont	CO
Valley Care Medical Center	Pleasanton	CA
Tom K Lee, Incorporated	Oakland	CA
Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	CA
Kaiser Permanente Medical Facility - Stockton	Stockton	CA
Kaiser Permanente Medical Center - Vallejo	Vallejo	CA
Kaiser Permanente Medical Center - South San Francisco	South San Francisco	CA
Kaiser Permanente Medical Center - Santa Teresa	San Jose	CA
Larry G Strieff MD Medical Corporation	Oakland	CA
Pacific Shores Medical Group - Long Beach	Long Beach	CA
St. Joseph Hospital Regional Cancer Center - Orange	Orange	CA
South Sacramento Kaiser-Permanente Medical Center	Sacramento	CA
Scripps Cancer Center - San Diego	La Jolla	CA
Salinas Valley Memorial Hospital	Salinas	CA
Penrose Cancer Center at Penrose Hospital	Colorado Springs	CO
Porter Adventist Hospital	Denver	CO
Herbert D. Kerman Regional Oncology Center - Daytona Beach	Daytona Beach	FL
M.D. Anderson Cancer Center at Orlando	Orlando	FL
Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	FL
Broward General Medical Center Cancer Center	Fort Lauderdale	FL
Baptist Cancer Institute - Jacksonville	Jacksonville	FL
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	GA
Hawaii Medical Center - East	Honolulu	HI
Kapiolani Medical Center at Pali Momi	Aiea	HI
Cancer Research Center of Hawaii	Honolulu	HI
Phoebe Cancer Center at Phoebe Putney Memorial Hospital	Albany	GA
Northeast Georgia Medical Center	Gainesville	GA
Tunnell Cancer Center at Beebe Medical Center	Lewes	DE
CCOP - Christiana Care Health Services	Newark	DE
St. Anthony Central Hospital	Denver	CO
St. Joseph Hospital	Denver	CO
Sky Ridge Medical Center	Lone Tree	CO
Rose Medical Center	Denver	CO
Presbyterian - St. Luke's Medical Center	Denver	CO
St. Mary - Corwin Regional Medical Center	Pueblo	CO
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	CO
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
Helen and Harry Gray Cancer Center at Hartford Hospital	Hartford	CT
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
Swedish Medical Center
Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	CA
Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	CA
St. Mary's Hospital Medical Center - Green Bay	Green Bay	WI
St. Vincent Hospital Regional Cancer Center	Green Bay	WI
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	WI
Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	WI
Diagnostic and Treatment Center	Schofield	WI
Hopedale Medical Complex	Hopedale	IL
Kootenai Cancer Center - Coeur d'Alene	Coeur D Alene	ID
Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	CA
James Graham Brown Cancer Center at University of Louisville	Louisville	KY
George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut
Danville Regional Medical Center	Danville	VA
Union Hospital Cancer Program at Union Hospital	Elkton	MD
Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	WI
Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	WI
Independence Regional Health Center
Veterans Affairs Medical Center - Dayton	Dayton	OH
Avera Cancer Institute	Sioux Falls	SD
Clinton Memorial Hospital
Clemens Regional Medical Center	Mount Clemens	Michigan
CancerCare of Maine at Eastern Maine Medical Center	Bangor	ME
Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	CA
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	FL
Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	FL
CCOP - Mount Sinai Medical Center	Miami Beach	FL
Sibley Memorial Hospital	Washington	DC
Barbara Ann Karmanos Cancer Institute
North Kansas City Hospital
Kaiser Foundation Hospital - San Rafael	San Rafael	CA
Kaiser Permanente - Fremont	Fremont	CA
Highland General Hospital	Oakland	CA
El Camino Hospital Cancer Center	Mountain View	CA
Eden Medical Center	Castro Valley	CA
Kaiser Permanente Medical Center - Hayward	Hayward	CA
Kaiser Permanente Medical Center - Oakland	Oakland	CA
Kaiser Permanente Medical Center - Sacramento	Sacramento	CA
Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	CA
Kaiser Permanente Medical Center - Roseville	Roseville	CA
Kaiser Permanente Medical Center - Richmond	Richmond	CA
Kaiser Permanente Medical Center - Redwood City	Redwood City	CA
East Bay Radiation Oncology Center	Castro Valley	CA
Doctors Medical Center - San Pablo Campus	San Pablo	CA
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	AR
Alta Bates Summit Medical Center - Summit Campus	Oakland	CA
Hopital du Saint-Sacrement - Quebec	Quebec City	Quebec
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	PA
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
Bay Area Breast Surgeons, Incorporated	Oakland	CA
Breastlink Medical Group, Incorporated at Long Beach Memorial Medical Center	Long Beach	CA
Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	CA
Contra Costa Regional Medical Center	Martinez	CA
CCOP - Bay Area Tumor Institute	Oakland	CA
Cancer Care Associates	Oklahoma City	OK
Kapiolani Medical Center for Women and Children	Honolulu	HI
Maui Memorial Medical Center	Wailuku	HI
Lucille P. Markey Cancer Center at University of Kentucky	Lexington	KY
CCOP - Ochsner	New Orleans	LA
Louisville Oncology at Norton Cancer Institute - Louisville	Louisville	KY
Cancer Resource Center at King's Daughters Medical Center	Ashland	KY
Wesley Medical Center
Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	LA
MBCCOP - LSU Health Sciences Center	New Orleans	LA
Tulane Cancer Center Office of Clinical Research	Alexandria	LA
York Hospital's Oncology Treatment Center	York	ME
Ochsner Health Center - Bluebonnet	Baton Rouge	LA
Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	LA
Medical Center of Louisiana - New Orleans	New Orleans	LA
Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	KS
Southwest Medical Center	Liberal	KS
Cancer Center of Kansas, PA - Wellington	Wellington	KS
Cancer Center of Kansas, PA - Winfield	Winfield	KS
Cancer Center of Kansas, PA - Salina	El Dorado	KS
Cancer Center of Kansas, PA - Pratt	Pratt	KS
Cancer Center of Kansas, PA - Parsons	Parsons	KS
Cancer Center of Kansas-Independence	Independence	KS
CCOP - Wichita	Wichita	KS
Shawnee Mission Medical Center	Shawnee Mission	KS
Saint Luke's Hospital - South	Overland Park	KS
Menorah Medical Center	Overland Park	KS
Lawrence Memorial Hospital	Lawrence	KS
Associates in Oncology and Hematology - Medical Center Drive	Gaithersburg	MD
Associates in Oncology and Hematology	Chattanooga	TN
Great Lakes Cancer Institute at McLaren Regional Medical Center	Flint	MI
Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	MI
Genesys Hurley Cancer Institute	Flint	MI
Foote Memorial Hospital	Jackson	MI
Community Cancer Center of Monroe	Monroe	MI
Hickman Cancer Center at Bixby Medical Center	Adrian	MI
Hurley Medical Center	Flint	MI
Mercy Regional Cancer Center at Mercy Hospital	Port Huron	MI
Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	MI
Mercy Memorial Hospital - Monroe	Monroe	MI
Lapeer Regional Hospital	Lapeer	MI
Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	MI
CCOP - Michigan Cancer Research Consortium	Ann Arbor	MI
Bronson Methodist Hospital	Kalamazoo	MI
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Rosedale	MD
Mercy Medical Center	Baltimore	MD
Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	MD
Greater Baltimore Medical Center Cancer Center	Towson	MD
Frederick Memorial Hospital Regional Cancer Therapy Center	Frederick	MD
Peninsula Regional Medical Center	Salisbury	MD
St. Agnes Hospital Cancer Center	Baltimore	MD
Breslin Cancer Center at Ingham Regional Medical Center	Lansing	MI
Borgess Medical Center	Kalamazoo	MI
Sturdy Memorial Hospital	Attleboro	MA
MetroWest Medical Center - Framingham Union Hospital	Framingham	MA
Cancer Center of Kansas, PA - Newton	Newton	KS
Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	KS
Good Samaritan Regional Health Center	Mount Vernon	IL
Graham Hospital
Galesburg Cottage Hospital
Galesburg Clinic, PC	Galesburg	IL
Eureka Community Hospital	Eureka	IL
Illinois Valley Community Hospital
John H. Stroger, Jr. Hospital of Cook County	Chicago	IL
Methodist Medical Center of Illinois
Mount Sinai Hospital Medical Center	Chicago	IL
Memorial Hospital	Carthage	IL
McDonough District Hospital	Macomb	IL
Mason District Hospital
Edward Hospital Cancer Center	Naperville	IL
Decatur Memorial Hospital Cancer Care Institute	Decatur	IL
Queen's Cancer Institute at Queen's Medical Center	Honolulu	HI
Straub Clinic and Hospital, Incorporated	Honolulu	HI
Pacific Cancer Institute - Maui	Wailuku	HI
OnCare Hawaii, Incorporated - Lusitana	Honolulu	HI
OnCare Hawaii, Incorporated - Kuakini	Honolulu	HI
Alexian Brothers Radiation Oncology	Elk Grove Village	IL
BroMenn Regional Medical Center	Normal	IL
Community Hospital of Ottawa	Ottawa	IL
Community Cancer Center	Normal	IL
CCOP - Illinois Oncology Research Association	Peoria	IL
Cancer Treatment Center at Pekin Hospital	Pekin	IL
Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	IL
Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	IL
McFarland Clinic, PC	Ames	IA
Associates in Womens Health, PA - North Review	Wichita	KS
Holden Comprehensive Cancer Center at University of Iowa	Iowa City	IA
St. Vincent Indianapolis Hospital	Indianapolis	IN
St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	IN
Cancer Center of Kansas - Fort Scott	Fort Scott	KS
Cancer Center of Kansas, PA - Kingman	Kingman	KS
Cancer Center of Kansas, PA - El Dorado	El Dorado	KS
Cancer Center of Kansas, PA - Dodge City	Dodge City	KS
Cancer Center of Kansas, PA - Chanute	Chanute	KS
Cancer Center of Kansas, PA - Wichita	Wichita	KS
Reid Hospital & Health Care Services	Richmond	IN
Fort Wayne Medical Oncology and Hematology	Fort Wayne	IN
Regional Cancer Center at Memorial Medical Center	Springfield	IL
Rush University Medical Center	Chicago	IL
Proctor Hospital	Peoria	IL
Perry Memorial Hospital	Princeton	IL
OSF St. Francis Medical Center	Peoria	IL
Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	IL
St. Joseph Medical Center	Kansas City	MO
Community Hospital	Munster	IN
Center for Cancer Care at Goshen General Hospital	Goshen	IN
Swedish-American Regional Cancer Center	Rockford	IL
St. Margaret's Hospital	Spring Valley	IL
Joliet Oncology-Hematology Associates, Limited - West	Joliet	IL

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed invasive adenocarcinoma of the breast

Primary breast tumor must be palpable and measure �� 2.0 cm on physical exam

No stage T4 disease

No ipsilateral cN2b or cN3 disease

cN1 or cN2a disease allowed

Histology confirmed by core-needle biopsy

No prior surgical axillary staging procedure

Fine-needle aspiration or core biopsy of an axillary node allowed

Pre-neoadjuvant therapy sentinel lymph node biopsy allowed if axillary nodes clinically negative

HER2-negative disease by immunohistochemistry (< 3+) or by fluorescent in situ hybridization (negative for gene amplification)

No prior excisional or incisional biopsy for primary breast tumor

No synchronous bilateral breast cancer (invasive or ductal carcinoma in situ [DCIS])

No prior breast cancer, including DCIS

Prior lobular carcinoma in situ allowed

No clinical or radiologic evidence of metastatic disease

Hormone receptor status known

PATIENT CHARACTERISTICS:

Female

Menopausal status not specified

ECOG performance status 0-1

Not pregnant or nursing

Negative pregnancy test

LVEF �� the lower limit of normal or �� 50% by MUGA or echocardiogram within the past 3 months

Absolute neutrophil count �� 1,200/mm��

Platelet count �� 100,000/mm��

Hemoglobin �� 10 g/dL

Alkaline phosphatase �� 2.5 times upper limit of normal (ULN)

AST �� 1.5 times ULN

Alkaline phosphatase and AST must not both be > ULN

Patients with either skeletal pain or alkaline phosphatase that is > ULN but �� 2.5 times ULN are allowed if bone scans do not demonstrate metastatic disease

AST or alkaline phosphatase > ULN allowed if liver imaging does not demonstrate metastatic disease

Bilirubin normal (�� 1.5 times ULN for Gilbert's disease or similar syndrome)

Serum creatinine �� ULN

Creatinine clearance > 50 mL/min

Urine protein:urine creatinine ratio < 1.0

Able to swallow oral medications

No other malignancies except carcinoma in situ of the cervix or colon, melanoma in situ, or basal cell or squamous cell carcinoma of the skin, unless the patient is considered to be disease-free for the past 5 years and at low-risk for recurrence

No cardiovascular-related condition that would preclude the use of anthracyclines, including any of the following:

Angina pectoris that requires the use of antianginal medication

History of documented congestive heart failure

Serious cardiac arrhythmia requiring medication

Severe conduction abnormality

Valvular disease with documented cardiac function compromise

Uncontrolled hypertension, defined as blood pressure > 150/90 mm Hg on antihypertensive therapy

Hypertension well controlled with medication allowed

No history of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular function

No history of transient ischemic attack or cerebrovascular accident

No arterial thrombotic event within the past 12 months

No symptomatic peripheral vascular disease

No significant nontraumatic bleeding within the past 6 months

No significant traumatic injury within the past 28 days

No serious or nonhealing wound, skin ulcers, or incompletely healed bone fracture

No active (by endoscopy) gastroduodenal ulcer(s)

No known bleeding diathesis or coagulopathy

Patients on warfarin with an in-range INR (between 2 and 3) allowed

No sensory or motor neuropathy �� grade 2

No conditions that would prohibit administration of corticosteroids

No history of severe hypersensitivity reaction to drugs formulated with polysorbate 80

No other nonmalignant systemic disease that would preclude study treatment or prevent required follow-up

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

No prior radiation therapy, chemotherapy, biologic therapy, and/or hormonal therapy for the currently diagnosed breast cancer

No prior anthracyclines, taxanes, capecitabine, fluorouracil, gemcitabine hydrochloride, or bevacizumab for any malignancy

No investigational agents within the past 30 days

No major surgical procedure or open biopsy within the past 28 days

Placement of a vascular access device is not considered a major surgical procedure

No concurrent sex hormone therapy (e.g., birth control pills, ovarian hormone replacement therapy)

No concurrent hormonal agent, such as raloxifene, tamoxifen, or other selective estrogen-receptor modulator (SERM), either for osteoporosis or breast cancer prevention

No major surgical procedures (other than the required breast surgery) during the course of the study

No other concurrent anticancer therapy

No concurrent partial breast radiation therapy and brachytherapy

No concurrent participation in other clinical trials employing an investigational agent

Contact