Chemotherapy in Treating Women With Breast Cancer That Can Be Surgically Removed

NCT00002707 | Completed Phase 3 DMC

• 2 other identifiers: NSABP B-27CDR0000064521
• Study Type: interventional
• Target: 2,411
• Locations: 2 countries
• Sites: 145

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if chemotherapy given before surgery is more effective with or without docetaxel given before or after surgery for breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy using doxorubicin and cyclophosphamide with or without docetaxel in treating women who have stage II or stage III breast cancer.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Outcome Measures

Primary Outcomes (1)

• Determine if 4 cycle of pre-op or post-op Taxotere given after 4 cycles of pre-op AC will more effectively prolong survival (S) than does 4 cycles of pre-op AC alone.

  Time from randomization to death from any cause.

Secondary Outcomes (5)

• Prolonging disease-free survival (DFS).

  Time from randomization to first related event of inoperable disease; residual disease following surgery; local, regional or distant recurrence; second primary cancer; death from any cause other than cancer.

• Clinical loco-regional tumor response to preoperative chemotherapy.

  3-4 weeks after the last cycle of pre-op chemotherapy.

• Pathologic loco-regional tumor response to pre-op chemotherapy.

  At time of surgery.

• Breast conservation assessment.

  Assessed following surgery.

• Evaluate if post-op Taxotere is of benefit in patients who received pre-op AC and, if so, whether it is of benefit in certain subgroups of patients.

  DFS and S will be assessed in patient subgroups.

Study Arms (3)

Group 2

EXPERIMENTAL

doxorubicin and cyclophosphamide plus Taxotere prior to surgery plus tamoxifen

Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Tamoxifen

Group 3

EXPERIMENTAL

doxorubicin and cyclophosphamide followed by surgery followed by taxotere plus tamoxifen

Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Tamoxifen

Group 1

ACTIVE COMPARATOR

doxorubicin and cyclophosphamide plus tamoxifen

Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Tamoxifen

Interventions

Cyclophosphamide DRUG

600 mg/m2 IV every 21 days for 4 cycles

Group 1; Group 2; Group 3

Docetaxel DRUG

100 mg/m2 IV every 21 days for 4 cycles

Group 2; Group 3

Doxorubicin DRUG

60 mg/m2 IV every 21 days fo 4 cycles

Group 1; Group 2; Group 3

Tamoxifen DRUG

20 mg p.o. once daily for 5 years starting on day 1 of ther first AC cycle

Group 1; Group 2; Group 3

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: Histologically or cytologically proven invasive adenocarcinoma of the breast Fine-needle aspiration is acceptable Core or Tru-cut biopsies are preferable No more than 63 days between initial diagnosis and randomization Tumor palpable on clinical exam and confined to the breast and ipsilateral axilla If clinically negative axillary nodes (N0): primary tumor greater than 1 cm (T1c-T3) If clinically positive axillary nodes (N1): any size primary tumor (T1-3) No N2 disease, i.e., ipsilateral nodes clinically fixed to one another or to other structures No skeletal pain unless: Bone scan and/or roentgenologic exam negative for metastatic disease Suspicious findings confirmed as benign by x-ray, MRI, or biopsy No ulceration, erythema, skin infiltration (complete fixation), or peau d'orange, or skin edema of any magnitude Tethering or dimpling of skin or nipple inversion allowed No bilateral malignancy Suspicious contralateral mass proven benign on biopsy allowed None of the following unless proven benign on biopsy: Suspicious palpable nodes in contralateral axilla Palpable supraclavicular or infraclavicular nodes Hormone receptor status: Any status PATIENT CHARACTERISTICS: Age: Any age Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: At least 10 years (exclusive of cancer diagnosis) Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal AST/ALT normal Alkaline phosphatase normal Renal: Creatinine normal Cardiovascular: No active cardiac disease that would preclude doxorubicin, e.g.: Documented myocardial infarction History of congestive heart failure Angina pectoris requiring medication Valvular disease with documented cardiac function compromise Arrhythmia associated with heart failure or cardiac dysfunction Poorly controlled hypertension, i.e., diastolic blood pressure greater than 100 mm Hg Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG unless left ventricular ejection fraction at least 45% by MUGA Other: No other malignancy within the past 10 years except: Segmentally resected lobular carcinoma in situ of the ipsilateral or contralateral breast Effectively treated nonmelanomatous skin cancer Surgically treated carcinoma in situ of the cervix No systemic disease that would preclude therapy No psychiatric or addictive disorder that would preclude informed consent Geographically accessible for follow-up Not pregnant PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer No prior anthracyclines for any malignancy No concurrent sex hormones (e.g., birth control pills or ovarian replacement therapy)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• National Cancer Institute (NCI): collaborator

Study Sites (145)

Huntsville Hospital System

Huntsville, Alabama, 35801, United States

Location

CCOP - Greater Phoenix

Phoenix, Arizona, 85006-2726, United States

Location

Sutter Health Western Division Cancer Research Group

Greenbrae, California, 94904, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Saint Mary Medical Center - Long Beach

Long Beach, California, 90813-0887, United States

Location

Beckman Research Institute, City of Hope

Los Angeles, California, 91010, United States

Location

CCOP - Bay Area Tumor Institute

Oakland, California, 94609-3305, United States

Location

Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Comprehensive Cancer Centers of the Desert

Palm Springs, California, 92262, United States

Location

Kaiser Permanente-Southern California Permanente Medical Group

San Diego, California, 92120, United States

Location

Catholic Healthcare West - Westbay Region

San Francisco, California, 94107-1728, United States

Location

CCOP - Santa Rosa Memorial Hospital

Santa Rosa, California, 95403, United States

Location

Kaiser Permanente Medical Center - Vallejo

Vallejo, California, 94589, United States

Location

CCOP - Colorado Cancer Research Program, Inc.

Denver, Colorado, 80209-5031, United States

Location

University of Colorado Cancer Center

Denver, Colorado, 80262, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06360-7106, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102-5037, United States

Location

CCOP - Christiana Care Health Services

Wilmington, Delaware, 19899, United States

Location

George Washington University Cancer Center

Washington D.C., District of Columbia, 20037, United States

Location

Halifax Medical Center

Daytona Beach, Florida, 32114, United States

Location

Baptist Regional Cancer Institute - Jacksonville

Jacksonville, Florida, 32207, United States

Location

Sylvester Cancer Center, University of Miami

Miami, Florida, 33136, United States

Location

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Good Samaritan Medical Center

West Palm Beach, Florida, 33401, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

CCOP - Atlanta Regional

Atlanta, Georgia, 30342-1701, United States

Location

Medical College of Georgia Comprehensive Cancer Center

Augusta, Georgia, 30912-4000, United States

Location

Dwight David Eisenhower Army Medical Center

Fort Gordon, Georgia, 30905-5650, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 96813, United States

Location

North Idaho Cancer Center

Coeur d'Alene, Idaho, 83814, United States

Location

Illinois Masonic Medical Center

Chicago, Illinois, 60657, United States

Location

CCOP - Evanston

Evanston, Illinois, 60201, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61602, United States

Location

Rockford Clinic

Rockford, Illinois, 61103, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

St. Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309-1016, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214-3882, United States

Location

Lucille Parker Markey Cancer Center, University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

Norton Healthcare System

Louisville, Kentucky, 40202-5070, United States

Location

Louisiana State University Medical Center - New Orleans

New Orleans, Louisiana, 70112, United States

Location

Tulane University School of Medicine

New Orleans, Louisiana, 70112, United States

Location

CCOP - Ochsner

New Orleans, Louisiana, 70121, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Franklin Square Hospital Center

Baltimore, Maryland, 21237, United States

Location

National Naval Medical Center

Bethesda, Maryland, 20889-5000, United States

Location

Regional Cancer Therapy Center - Frederick

Frederick, Maryland, 21701, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Lahey Clinic - Burlington

Burlington, Massachusetts, 01805, United States

Location

Berkshire Medical Center

Pittsfield, Massachusetts, 01201, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

CCOP - Ann Arbor Regional

Ann Arbor, Michigan, 48106, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

CCOP - Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

CCOP - Kalamazoo

Kalamazoo, Michigan, 49007-3731, United States

Location

Providence Hospital - Southfield

Southfield, Michigan, 48075-9975, United States

Location

CCOP - Duluth

Duluth, Minnesota, 55805, United States

Location

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, 55415, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, 65203, United States

Location

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, 65807, United States

Location

St. Louis University School of Medicine

St Louis, Missouri, 63104, United States

Location

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, 63141, United States

Location

CCOP - Montana Cancer Consortium

Billings, Montana, 59101, United States

Location

Methodist Cancer Center - Omaha

Omaha, Nebraska, 68114, United States

Location

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, 68131, United States

Location

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Cooper Cancer Institute

Camden, New Jersey, 08103, United States

Location

Trinitas Hospital - Jersey Street Campus

Elizabeth, New Jersey, 07201, United States

Location

CCOP - Northern New Jersey

Hackensack, New Jersey, 07601, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Cancer Institute of New Jersey at Hamilton

Hamilton, New Jersey, 08690, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

University of Medicine and Dentistry of New Jersey

Newark, New Jersey, 07103-2425, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Overlook Hospital

Summit, New Jersey, 07902-0220, United States

Location

University of New Mexico Cancer Research & Treatment Center

Albuquerque, New Mexico, 87131, United States

Location

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, 13210, United States

Location

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, 27599-7295, United States

Location

East Carolina University School of Medicine

Greenville, North Carolina, 27858-4354, United States

Location

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, 27104-4241, United States

Location

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157-1082, United States

Location

CCOP - Merit Care Hospital

Fargo, North Dakota, 58122, United States

Location

Akron City Hospital

Akron, Ohio, 44309, United States

Location

Aultman Cancer Center

Canton, Ohio, 44710, United States

Location

Barrett Cancer Center, The University Hospital

Cincinnati, Ohio, 45219, United States

Location

Jewish Hospital of Cincinnati, Inc.

Cincinnati, Ohio, 45236, United States

Location

South Pointe Hospital

Cleveland, Ohio, 44122, United States

Location

CCOP - Columbus

Columbus, Ohio, 43206, United States

Location

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, 43210, United States

Location

CCOP - Dayton

Kettering, Ohio, 45429, United States

Location

CCOP - Sooner State

Tulsa, Oklahoma, 74136, United States

Location

Oregon Cancer Center at Oregon Health Sciences University

Portland, Oregon, 97201-3098, United States

Location

CCOP - Columbia River Program

Portland, Oregon, 97213, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18105-1556, United States

Location

St. Luke's Network - Bethlehem

Bethlehem, Pennsylvania, 18015, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822-2001, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212-4772, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

Mercy Hospital Cancer Center - Scranton

Scranton, Pennsylvania, 18501, United States

Location

CCOP - MainLine Health

Wynnewood, Pennsylvania, 19096, United States

Location

York Hospital

York, Pennsylvania, 17315, United States

Location

Kent County Memorial Hospital - Rhode Island

Warwick, Rhode Island, 02886, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425-0721, United States

Location

CCOP - Greenville

Greenville, South Carolina, 29615, United States

Location

CCOP - Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, 57105-1080, United States

Location

CCOP - Baptist Cancer Institute

Memphis, Tennessee, 38117, United States

Location

Simmons Cancer Center - Dallas

Dallas, Texas, 75235-9154, United States

Location

Medical Group of Texas

Dallas, Texas, 75243, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-1329, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410-1894, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78284-7811, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Utah Valley Regional Medical Center - Provo

Provo, Utah, 84604, United States

Location

CCOP - Southwestern Vermont Regional Cancer Center

Bennington, Vermont, 05201, United States

Location

Vermont Cancer Center

Burlington, Vermont, 05401-3498, United States

Location

Virginia Oncology Associates

Newport News, Virginia, 23606, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

MBCCOP - Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

CCOP - Virginia Mason Research Center

Seattle, Washington, 98101, United States

Location

Puget Sound Oncology Consortium

Seattle, Washington, 98109, United States

Location

CCOP - Northwest

Tacoma, Washington, 98405-0986, United States

Location

David Lee Cancer Center

Charleston, West Virginia, 25304, United States

Location

West Virginia University Hospitals

Morgantown, West Virginia, 26506-9162, United States

Location

Camden-Clark Memorial Hospital

Parkersburg, West Virginia, 26102, United States

Location

St. Vincent Hospital

Green Bay, Wisconsin, 54307-3508, United States

Location

CCOP - Marshfield Medical Research and Education Foundation

Marshfield, Wisconsin, 54449, United States

Location

St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Tom Baker Cancer Center - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2L-4M1, Canada

Location

Royal Victoria Hospital - Montreal

Montreal, Quebec, H3A 1A1, Canada

Location

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Jewish General Hospital - Montreal

Montreal, Quebec, H3T 1E2, Canada

Location

St. Mary's Hospital Center

Montreal, Quebec, H3T 1M5, Canada

Location

Hopital du Saint-Sacrament, Quebec

Québec, Quebec, G1S 4L8, Canada

Location

L'Hopital Laval

Ste-Foy, Quebec, G1V 4G5, Canada

Location

Related Publications (9)

• Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85. doi: 10.1200/JCO.2007.15.0235.

  PMID: 18258986 BACKGROUND

• Soran A, Nesbitt L, Mamounas EP, Lembersky B, Bryant J, Anderson S, Brown A, Passarello M. Centralized medical monitoring in phase III clinical trials: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience. Clin Trials. 2006;3(5):478-85. doi: 10.1177/1740774506070747.

  PMID: 17060221 BACKGROUND

• Heys SD, Sarkar T, Hutcheon AW. Primary docetaxel chemotherapy in patients with breast cancer: impact on response and survival. Breast Cancer Res Treat. 2005 Mar;90(2):169-85. doi: 10.1007/s10549-004-1001-0.

  PMID: 15803364 BACKGROUND

• Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006 May 1;24(13):2019-27. doi: 10.1200/JCO.2005.04.1665. Epub 2006 Apr 10.

  PMID: 16606972 RESULT

• Julian T, Anderson S, Fourchotte V, et al.: Is invasive lobular breast cancer a prognostic factor for neoadjuvant chemotherapy response and long term outcomes? [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3065, S146, 2006.

  RESULT

• Mamounas EP, Brown A, Anderson S, Smith R, Julian T, Miller B, Bear HD, Caldwell CB, Walker AP, Mikkelson WM, Stauffer JS, Robidoux A, Theoret H, Soran A, Fisher B, Wickerham DL, Wolmark N. Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2005 Apr 20;23(12):2694-702. doi: 10.1200/JCO.2005.05.188.

  PMID: 15837984 RESULT

• Bear HD, Anderson S, Smith RE, et al.: A randomized trial comparing preoperative (preop) doxorubicin/cyclophosphamide (AC) to preop AC followed by preop docetaxel (T) and to preop AC followed by postoperative (postop) T in patients (pts) with operable carcinoma of the breast: results of NSABP B-27. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-26, 2004.

  RESULT

• Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N; National Surgical Adjuvant Breast and Bowel Project Protocol B-27. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003 Nov 15;21(22):4165-74. doi: 10.1200/JCO.2003.12.005. Epub 2003 Oct 14.

  PMID: 14559892 RESULT

• Mamounas EP, Brown A, Smith R, et al.: Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: updated results from NSABP B-27. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-140, 2002.

  RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Docetaxel; Doxorubicin; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Stilbenes; Benzylidene Compounds; Benzene Derivatives

Study Officials

• Harry D. Bear, MD, PhD

  Massey Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: May 21, 2004
• Study Start: December 1, 1995
• Primary Completion: June 1, 2002
• Study Completion: February 1, 2010
• Last Updated: February 3, 2010

Record last verified: 2010-02

Locations

US (134); CA (11)