Combination Chemotherapy in Treating Women With Stage I, Stage II, or Stage IIIA (cT1-3, N0-1, M0) Breast Cancer and Positive Axillary Lymph Nodes

Breast Cancer Clinical Trial

Official title:

A Three-Arm Randomized Trial to Compare Adjuvant Adriamycin and Cyclophosphamide Followed by Taxotere (AC-T); Adriamycin and Taxotere (AT); and Adriamycin, Taxotere, and Cyclophosphamide (ATC) in Breast Cancer Patients With Positive Axillary Lymph Nodes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003782
• Other study ID #: NSABP B-30
• Secondary ID: CDR0000066914
• Status: Completed
• Phase: Phase 3
• Start date: March 1999
• Est. completion date: December 2012

Study information

• Verified date: March 2024
• Source: NSABP Foundation Inc
• Contact: n/a
• Is FDA regulated: No
• 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. Giving combination chemotherapy after surgery may kill any tumor cells remaining following surgery. It is not yet known which regimen of combination chemotherapy is more effective in treating breast cancer with positive axillary lymph nodes.

PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy in treating women who have undergone surgery for stage I, stage II, or stage IIIA breast cancer with positive axillary lymph nodes.

Description:

OBJECTIVES:

• Compare the efficacy of adjuvant doxorubicin, cyclophosphamide, and docetaxel given concurrently vs adjuvant doxorubicin and cyclophosphamide followed by docetaxel, in terms of overall survival and disease-free survival, of women with breast cancer and positive axillary lymph nodes.

• Compare the efficacy of adjuvant doxorubicin and docetaxel vs regimens containing cyclophosphamide in these patients.

• Compare the toxic effects of these regimens in these patients.

• Compare the quality of life of patients treated with these regimens. (Quality of life substudy closed to accrual as of 7/20/01.)

• Compare the differences in amenorrhea in premenopausal women in each treatment arm and its relationship to symptoms, quality of life (quality of life substudy closed to accrual as of 7/20/01), disease-free survival, and overall survival.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, number of positive nodes (1-3 vs 4-9 vs at least 10), sequential tamoxifen or anastrozole administration (yes vs no), and type of prior surgery and radiotherapy plan (mastectomy with no local or regional radiotherapy vs mastectomy with local and/or regional radiotherapy vs lumpectomy with local radiotherapy vs lumpectomy with local and regional radiotherapy). Patients are randomized to one of three treatment arms.

• Arm 1: Patients receive doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes every 21 days for 4 courses. Three weeks after the last dose of this combination, patients receive docetaxel IV over 1 hour every 21 days for 4 courses.

• Arm 2: Patients receive doxorubicin IV over 15 minutes and docetaxel IV over 1 hour every 21 days for 4 courses.

• Arm 3: Patients receive doxorubicin IV over 15 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour every 21 days for 4 courses.

Patients in all arms who are estrogen receptor-positive and/or progesterone receptor-positive receive oral tamoxifen daily for 5 years beginning within 3-12 weeks of completion of chemotherapy. Patients who are postmenopausal may receive alternative hormonal therapy at the discretion of the treating physician.

Some patients may receive postmastectomy radiotherapy on SWOG-S9927 or NCIC-MA.20 after recovery from chemotherapy.

Quality of life and menstrual history are assessed before randomization, on day 1 of course 4, and at 6, 12, 18, and 24 months. (Quality of life substudy closed to accrual as of 7/20/01.)

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 5,300 patients will be accrued for this study within 4-5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5351
• Est. completion date: December 2012
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive adenocarcinoma of the breast

• Confined to the breast and ipsilateral axilla on clinical exam

• Stage I, II, or IIIA (cT1-3, N0-1, M0)

• At least one axillary lymph node with evidence of tumor on histologic exam

• Sentinel node biopsy allowed if followed by axillary dissection

• No suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless proven on biopsy to not be involved with tumor

• No bilateral malignancy or mass in the opposite breast, unless mass is histologically proven to be benign

• Must have undergone either a prior total mastectomy and axillary dissection (modified radical mastectomy) OR

• Prior lumpectomy and axillary dissection

• Patients must receive radiotherapy after randomization (not before) AND after chemotherapy

• Margins must be clear

• No ipsilateral lymph nodes that are fixed to one another or to other structures (N2 disease) and/or any positive nonaxillary lymph nodes (intramammary nodes are considered axillary nodes)

• No histologically evident invasive tumor or ductal carcinoma in situ

• No diffuse tumors by mammography that would not be surgically amenable to lumpectomy

• No other dominant mass in the ipsilateral breast remnant unless one of the following is true:

• Histologically benign

• Surgically removed with clear margins if malignant

• No ulceration, erythema, infiltration of the skin or underlying chest wall (complete fixation), peau d'orange, or skin edema of any magnitude

• Tethering or dimpling of the skin or nipple inversion allowed

• No metastatic disease

• Skeletal pain allowed if bone scan negative for metastases

• Hormone receptor status:

• Estrogen and progesterone status determined

PATIENT CHARACTERISTICS:

Age:

• greater than or equal to 18 years

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• At least 10 years, excluding diagnosis of cancer

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3 (may be less, if in the opinion of the investigator, this represents an ethnic or racial variation)

• Platelet count at least 100,000/mm^3* NOTE: *If platelet count is above the upper limit of normal (ULN), significant underlying hematologic disorders must be excluded

Hepatic:

• Bilirubin no greater than ULN

• Alkaline phosphatase less than 2.5 times ULN*

• SGOT less than 1.5 times ULN*

• No nonmalignant systemic hepatic disease that would preclude study participation NOTE:

*Alkaline phosphatase and SGOT cannot both be greater than ULN

Renal:

• Creatinine no greater than normal

• No nonmalignant systemic renal disease that would preclude study participation

Cardiovascular:

• No nonmalignant systemic cardiovascular disease that would preclude study participation

• LVEF at least lower limit of normal (LLN) by MUGA or echocardiogram

• No active cardiac disease that would preclude use of doxorubicin or docetaxel, including the following:

• Any prior myocardial infarction

• Angina pectoris requiring anti-anginal medication

• History of congestive heart failure

• Cardiac arrhythmia requiring medication

• Severe conduction abnormality

• Valvular disease with documented cardiac function compromise

• Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG, unless LVEF at least LLN

• Poorly controlled hypertension (diastolic greater than 100 mm/Hg)

• Hypertension well controlled by medication allowed

Other:

• No grade 2 or greater peripheral neuropathy

• No other prior malignancy within the past 5 years except:

• Effectively treated squamous cell or basal cell skin cancer

• Surgically treated carcinoma in situ of the cervix

• Segmentally resected lobular carcinoma in situ of the ipsilateral or contralateral breast

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• No nonmalignant systemic disease that would preclude study participation

• No diabetes with morning fasting blood glucose of 200 mg/dL or greater

• No psychiatric or addictive disorders that would preclude informed consent

• No contraindication to corticosteroids that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy for breast cancer

Chemotherapy:

• No prior chemotherapy for breast cancer

• No prior anthracyclines or taxanes

• No other concurrent investigational chemotherapy

Endocrine therapy:

• No prior hormonal therapy for breast cancer

• No concurrent hormonal birth control methods or other hormonal therapy

• No concurrent raloxifene, including for osteoporosis

• Concurrent low-dose topical estrogen in the form of conjugated estrogen ring or conjugated estrogen vaginal cream (dose no more than 0.3 mg or 1/8 of an applicator applied vaginally 3 times a week) allowed

Radiotherapy:

• See Disease Characteristics

• No prior radiotherapy for this malignancy

Surgery:

• See Disease Characteristics

• No more than 84 days since prior surgery for breast cancer (e.g., lumpectomy, mastectomy, sentinel node biopsy, axillary dissection, or re-excision of lumpectomy margins)

Other:

• No prior systemic therapy for this malignancy

• No concurrent medications that alter cardiac conduction (e.g., digitalis, beta blockers, or calcium-channel blockers) for cardiac arrhythmia, angina, or congestive heart failure (allowed if administered for other reasons [e.g., hypertension])

• Concurrent bisphosphonates allowed

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• cyclophosphamide
Arm 1: 600 mg/m2 IV every 21 days for 4 cycles; Arm 3: 500 mg/m2 IV every 21 days for 4 cycles
• docetaxel
Arm 1: 100 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 75 mg/m2 IV every 21 days for 4 cycles
• doxorubicin
Arm 1: 60 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 50 mg/m2 IV every 21 days for 4 cycles

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center - Calgary	Calgary	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	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Hopital du Saint-Sacrement, Quebec	Quebec City	Quebec
Canada	St. Michael's Hospital - Toronto	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Akron City Hospital	Akron	Ohio
United States	New York Oncology Hematology, P.C. - Albany Regional Cancer Center	Albany	New York
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	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	Green Mountain Oncology Group	Bennington	Vermont
United States	National Naval Medical Center	Bethesda	Maryland
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Lincoln Medical and Mental Health Center	Bronx	New York
United States	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York
United States	Alamance Cancer Center	Burlington	North Carolina
United States	Lahey Clinic Medical Center - Burlington	Burlington	Massachusetts
United States	Aultman Hospital Cancer Center at Aultman Health Foundation	Canton	Ohio
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Charleston Area Medical Center	Charleston	West Virginia
United States	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Jewish Hospital of Cincinnati, Incorporated	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	North Idaho Cancer Center	Coeur d'Alene	Idaho
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Genesis Medical Center	Davenport	Iowa
United States	Halifax Medical Center	Daytona Beach	Florida
United States	CCOP - Central Illinois	Decatur	Illinois
United States	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Michigan State University	East Lansing	Michigan
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	University of Connecticut Cancer Center at University of Connecticut Health Center	Farmington	Connecticut
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	California Cancer Center	Fresno	California
United States	Charles R. Wood Foundation Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	CCOP - Greenville	Greenville	South Carolina
United States	Leo W. Jenkins Cancer Center of University Health Systems of Eastern Carolina	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	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	Comprehensive Cancer Institute	Huntsville	Alabama
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	St. Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Baptist Regional Cancer Institute - Jacksonville	Jacksonville	Florida
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	CCOP - Dayton	Kettering	Ohio
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Scripps Cancer Center at Scripps Clinic	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	Pacific Shores Medical Group	Long Beach	California
United States	Consultants in Blood Disorders and Cancer	Louisville	Kentucky
United States	Norton Healthcare Cancer Center	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Baptist Cancer Institute - Memphis at Baptist Memorial Hospital - Memphis	Memphis	Tennessee
United States	University of Miami Sylvester Cancer Center	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Community Hospital	Munster	Indiana
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans	New Orleans	Louisiana
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Virginia Oncology Associates - Newport News	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 Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center	Orange	California
United States	MD Anderson Cancer Center Orlando	Orlando	Florida
United States	Comprehensive Cancer Centers of the Desert	Palm Springs	California
United States	Stanford Cancer Center at Stanford University Medical Center	Palo Alto	California
United States	Camden-Clark Memorial Hospital	Parkersburg	West Virginia
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	CCOP - Western Regional, Arizona	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Berkshire Medical Center	Pittsfield	Massachusetts
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Reading Hospital and Medical Center	Reading	Pennsylvania
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	CCOP - Beaumont	Royal Oak	Michigan
United States	Sutter Cancer Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	St. Louis University Hospital Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	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	Sarasota Memorial Hospital	Sarasota	Florida
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	Providence Cancer Institute at Providence Hospital	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	Staten Island University Hospital	Staten Island	New York
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 - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center - Vallejo	Vallejo	California
United States	South Pointe Hospital - Cancer Care Center	Warrensville Heights	Ohio
United States	MBCCOP - Howard University Cancer Center	Washington	District of Columbia
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 at Wake Forest University	Winston-Salem	North Carolina
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Wellspan Health - York Cancer Center	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 (4)

Ganz PA, Land SR, Geyer CE, et al.: NSABP B-30: definitive analysis of quality of life (QOL) and menstrual history (MH) outcomes from a randomized trial evaluating different schedules and combinations of adjuvant therapy containing doxorubicin, docetaxel

Swain SM, Jeong JH, Geyer CE, et al.: NSABP B-30: definitive analysis of patient outcome from a randomized trial evaluating different schedules and combinations of adjuvant therapy containing doxorubicin, docetaxel and cyclophosphamide in women with opera

Swain SM, Land SR, Ritter MW, Costantino JP, Cecchini RS, Mamounas EP, Wolmark N, Ganz PA. Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial. Breast Cancer Res Treat. 2009 Jan;113(2):31 — View Citation

Swain SM, Land SR, Sundry R, et al.: Amenorrhea in premenopausal women on the doxorubicin (A) and cyclophosphamide (C) followed-by docetaxel (T) arm of NSABP B-30: preliminary results. [Abstract] J Clin Oncol 23 (Suppl 16): A-537, 13s, 2005.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		8 years
Primary	Disease Free Survival		time to event: breast cancer recurrence; second primary cancer; death from any cause as a first event
Secondary	Toxicities Among the 3 Regimens		9 years
Secondary	Quality of Life Among Breast Cancer Patients		baseline, 9 weeks, and 6, 12, 18, and 24 months
Secondary	Amenorrhea in Premenopausal Women		baseline, 9 weeks, and 6, 12, 18, and 24 months