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

Breast Cancer Clinical Trial

Official title:

A RANDOMIZED TRIAL COMPARING PREOPERATIVE DOXORUBICIN (ADRIAMYCIN)/CYCLOPHOSPHAMIDE (AC) TO PREOPERATIVE AC FOLLOWED BY PREOPERATIVE DOCETAXEL (TAXOTERE) AND TO PREOPERATIVE AC FOLLOWED BY POSTOPERATIVE DOCETAXEL IN PATIENTS WITH OPERABLE CARCINOMA OF THE BREAST

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002707
• Other study ID #: NSABP B-27
• Secondary ID: CDR0000064521
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: February 2, 2010
• Start date: December 1995
• Est. completion date: February 2010

Study information

• Verified date: February 2010
• Source: NSABP Foundation Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES: I. Compare overall and disease-free survival in patients with operable adenocarcinoma of the breast treated with 4 courses of preoperative doxorubicin and cyclophosphamide (AC) alone vs 4 courses of preoperative or postoperative docetaxel (TXT) following 4 courses of preoperative AC. II. Evaluate whether the addition of preoperative TXT to preoperative AC results in improved rates of clinical and pathologic locoregional tumor response. III. Assess whether the addition of preoperative TXT to preoperative AC results in improved rates of breast conservation. IV. Assess whether postoperative TXT improves disease-free and overall survival in patients who receive preoperative AC, especially in certain subgroups of patients (e.g., those with pathologically positive nodes).

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 50 vs 50 and over), clinical tumor size (less than 2.1 cm vs 2.1-4.0 cm vs greater than 4.0 cm), clinical nodal status (negative vs positive), and participating center. Patients are randomized to one of three treatment arms. Arm I: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1 every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After completion of chemotherapy, patients are offered surgery (e.g., lumpectomy with axillary node dissection, or modified radical mastectomy). Post-operative radiotherapy is given post-lumpectomy. Arm II: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours followed by docetaxel IV over 1 hour on day 1 once every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After the completion of chemotherapy, surgery is offered (as in arm I). Radiotherapy follows surgery in post-lumpectomy patients. Arm III: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1 every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After completion of chemotherapy, surgery is offered (as in arm I). After surgical recovery, docetaxel IV is given over 1 hour once every 21 days for 4 courses. Radiotherapy follows docetaxel in post-lumpectomy patients. Chemotherapy is repeated every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 2,400 patients will be accrued for this study within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2411
• Est. completion date: February 2010
• Est. primary completion date: June 2002
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Cyclophosphamide
600 mg/m2 IV every 21 days for 4 cycles
• Docetaxel
100 mg/m2 IV every 21 days for 4 cycles
• Doxorubicin
60 mg/m2 IV every 21 days fo 4 cycles
• Tamoxifen
20 mg p.o. once daily for 5 years starting on day 1 of ther first AC cycle

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Jewish General Hospital - Montreal	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Royal Victoria Hospital - Montreal	Montreal	Quebec
Canada	St. Mary's Hospital Center	Montreal	Quebec
Canada	Hopital du Saint-Sacrament, Quebec	Quebec City	Quebec
Canada	L'Hopital Laval	Ste-Foy	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Akron City Hospital	Akron	Ohio
United States	University of New Mexico Cancer Research & Treatment Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Medical College of Georgia Comprehensive Cancer Center	Augusta	Georgia
United States	Franklin Square Hospital Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	CCOP - Southwestern Vermont Regional Cancer Center	Bennington	Vermont
United States	National Naval Medical Center	Bethesda	Maryland
United States	St. Luke's Network - Bethlehem	Bethlehem	Pennsylvania
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Boston Medical Center	Boston	Massachusetts
United States	Lahey Clinic - Burlington	Burlington	Massachusetts
United States	Vermont Cancer Center	Burlington	Vermont
United States	Cooper Cancer Institute	Camden	New Jersey
United States	Aultman Cancer Center	Canton	Ohio
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	David Lee Cancer Center	Charleston	West Virginia
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Illinois Masonic Medical Center	Chicago	Illinois
United States	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio
United States	Jewish Hospital of Cincinnati, Inc.	Cincinnati	Ohio
United States	South Pointe Hospital	Cleveland	Ohio
United States	North Idaho Cancer Center	Coeur d'Alene	Idaho
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Medical Group of Texas	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Halifax Medical Center	Daytona Beach	Florida
United States	CCOP - Colorado Cancer Research Program, Inc.	Denver	Colorado
United States	University of Colorado Cancer Center	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	CCOP - Duluth	Duluth	Minnesota
United States	Michigan State University	East Lansing	Michigan
United States	Trinitas Hospital - Jersey Street Campus	Elizabeth	New Jersey
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Regional Cancer Therapy Center - Frederick	Frederick	Maryland
United States	University of Texas Medical Branch	Galveston	Texas
United States	CCOP - Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	CCOP - Greenville	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey
United States	Hartford Hospital	Hartford	Connecticut
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Huntsville Hospital System	Huntsville	Alabama
United States	St. Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Baptist Regional Cancer Institute - Jacksonville	Jacksonville	Florida
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Dayton	Kettering	Ohio
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Lucille Parker Markey Cancer Center, University of Kentucky	Lexington	Kentucky
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Saint Mary Medical Center - Long Beach	Long Beach	California
United States	Beckman Research Institute, City of Hope	Los Angeles	California
United States	Norton Healthcare System	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin
United States	CCOP - Baptist Cancer Institute	Memphis	Tennessee
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	Louisiana State University Medical Center - New Orleans	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	Virginia Oncology Associates	Newport News	Virginia
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Methodist Cancer Center - Omaha	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	Comprehensive Cancer Centers of the Desert	Palm Springs	California
United States	Camden-Clark Memorial Hospital	Parkersburg	West Virginia
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	CCOP - Greater Phoenix	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Berkshire Medical Center	Pittsfield	Massachusetts
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	Rockford Clinic	Rockford	Illinois
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	St. Louis University School of Medicine	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	Catholic Healthcare West - Westbay Region	San Francisco	California
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Puget Sound Oncology Consortium	Seattle	Washington
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Providence Hospital - Southfield	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Baystate Medical Center	Springfield	Massachusetts
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Overlook Hospital	Summit	New Jersey
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	CCOP - Northwest	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	CCOP - Sooner State	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center - Vallejo	Vallejo	California
United States	Kent County Memorial Hospital - Rhode Island	Warwick	Rhode Island
United States	George Washington University Cancer Center	Washington	District of Columbia
United States	Good Samaritan Medical Center	West Palm Beach	Florida
United States	CCOP - Wichita	Wichita	Kansas
United States	CCOP - Christiana Care Health Services	Wilmington	Delaware
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	York Hospital	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
NSABP Foundation Inc	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (9)

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 docet — View Citation

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 car

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 cyclop — View Citation

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. Review. — View Citation

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.

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 can — View Citation

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.

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. Erratum in: J Clin Oncol. 2008 Jun 1;26(16):2793. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No
Secondary	Clinical loco-regional tumor response to preoperative chemotherapy.		3-4 weeks after the last cycle of pre-op chemotherapy.	No
Secondary	Pathologic loco-regional tumor response to pre-op chemotherapy.		At time of surgery.	No
Secondary	Breast conservation assessment.		Assessed following surgery.	No
Secondary	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.	No