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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


Phase 3
18 Years
N/A
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Overall Survival

Outcome Time Frame:

8 years

Safety Issue:

No

Principal Investigator

Norman Wolmark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NSABP Foundation, Inc.

Authority:

United States: Federal Government

Study ID:

NSABP B-30

NCT ID:

NCT00003782

Start Date:

March 1999

Completion Date:

December 2012

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • Breast Neoplasms

Name

Location

Akron City HospitalAkron, Ohio  44304
Baylor College of MedicineHouston, Texas  77030
National Naval Medical CenterBethesda, Maryland  20889
Rush-Presbyterian-St. Luke's Medical CenterChicago, Illinois  60612
Arthur G. James Cancer Hospital - Ohio State UniversityColumbus, Ohio  43210
CCOP - Upstate CarolinaSpartanburg, South Carolina  29303
St. Luke's Medical CenterMilwaukee, Wisconsin  53215
CCOP - WichitaWichita, Kansas  67214-3882
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
CCOP - Atlanta RegionalAtlanta, Georgia  30342-1701
CCOP - Kansas CityKansas City, Missouri  64131
CCOP - Missouri Valley Cancer ConsortiumOmaha, Nebraska  68131
CCOP - Southern Nevada Cancer Research FoundationLas Vegas, Nevada  89106
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
CCOP - Southeast Cancer Control ConsortiumWinston-Salem, North Carolina  27104-4241
MBCCOP - Massey Cancer CenterRichmond, Virginia  23298-0037
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Carle Cancer CenterUrbana, Illinois  61801
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
CCOP - KalamazooKalamazoo, Michigan  49007-3731
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
CCOP - Northern New JerseyHackensack, New Jersey  07601
St. Vincent Hospital and Health Care CenterIndianapolis, Indiana  46260
Methodist Cancer Center at Methodist HospitalIndianapolis, Indiana  46202
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
CCOP - DuluthDuluth, Minnesota  55805
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
MD Anderson Cancer Center OrlandoOrlando, Florida  32806
CCOP - OchsnerNew Orleans, Louisiana  70121
CCOP - Merit Care HospitalFargo, North Dakota  58122
Comprehensive Cancer Center at Wake Forest UniversityWinston-Salem, North Carolina  27157-1082
California Cancer CenterFresno, California  93720
Sutter Health Western Division Cancer Research GroupGreenbrae, California  94904
CCOP - Bay Area Tumor InstituteOakland, California  94609-3305
CCOP - Santa Rosa Memorial HospitalSanta Rosa, California  95403
Halifax Medical CenterDaytona Beach, Florida  32114
CCOP - Central IllinoisSpringfield, Illinois  62526
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
Newark Beth Israel Medical CenterNewark, New Jersey  07112
CCOP - ColumbusColumbus, Ohio  43206
CCOP - DaytonKettering, Ohio  45429
Albert Einstein Cancer CenterPhiladelphia, Pennsylvania  19141
Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Mercy Hospital Cancer Center - ScrantonScranton, Pennsylvania  18501
CCOP - MainLine HealthWynnewood, Pennsylvania  19096
CCOP - GreenvilleGreenville, South Carolina  29615
Joe Arrington Cancer Research and Treatment CenterLubbock, Texas  79410-1894
Green Mountain Oncology GroupRutland, Vermont  05701
CCOP - Western Regional, ArizonaPhoenix, Arizona  85006-2726
Chao Family Comprehensive Cancer Center at University of California Irvine Cancer CenterOrange, California  92868
University of Colorado Cancer Center at University of Colorado Health Sciences CenterDenver, Colorado  80010
CCOP - EvanstonEvanston, Illinois  60201
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
CCOP - Grand RapidsGrand Rapids, Michigan  49503
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
MBCCOP - University of New Mexico HSCAlbuquerque, New Mexico  87131
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Charles M. Barrett Cancer Center at University HospitalCincinnati, Ohio  45267-0526
CCOP - Columbia River Oncology ProgramPortland, Oregon  97225
Kimmel Cancer Center at Thomas Jefferson University - PhiladelphiaPhiladelphia, Pennsylvania  19107
CCOP - Scott and White HospitalTemple, Texas  76508
CCOP - St. Vincent Hospital Cancer Center, Green BayGreen Bay, Wisconsin  54301
Baptist Regional Cancer Institute - JacksonvilleJacksonville, Florida  32207
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Dwight David Eisenhower Army Medical CenterFort Gordon, Georgia  30905-5650
CCOP - St. Louis-Cape GirardeauSaint Louis, Missouri  63141
CCOP - Virginia Mason Research CenterSeattle, Washington  98101
CCOP - NorthwestTacoma, Washington  98405-0986
Puget Sound Oncology ConsortiumSeattle, Washington  98109
Sutter Cancer CenterSacramento, California  95816
Kaiser Permanente Medical Center - VallejoVallejo, California  94589
Hartford HospitalHartford, Connecticut  06102-5037
Sarasota Memorial HospitalSarasota, Florida  34239
Medical College of Georgia Comprehensive Cancer CenterAugusta, Georgia  30912-4000
Eastern Maine Medical CenterBangor, Maine  04401
Franklin Square Hospital CenterBaltimore, Maryland  21237
Berkshire Medical CenterPittsfield, Massachusetts  01201
Baystate Medical CenterSpringfield, Massachusetts  01199
Michigan State UniversityEast Lansing, Michigan  48824
Staten Island University HospitalStaten Island, New York  10305
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.Syracuse, New York  13217
CCOP - OklahomaTulsa, Oklahoma  74136
Allegheny General HospitalPittsburgh, Pennsylvania  15212-4772
Utah Valley Regional Medical Center - ProvoProvo, Utah  84604
Virginia Oncology Associates - Newport NewsNewport News, Virginia  23606
Eastern Virginia Medical SchoolNorfolk, Virginia  23507
Oncology and Hematology Associates of Southwest Virginia, Inc.Roanoke, Virginia  24014
Camden-Clark Memorial HospitalParkersburg, West Virginia  26102
Providence Alaska Medical CenterAnchorage, Alaska  99508
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San DiegoSan Diego, California  92120
City of Hope Comprehensive Cancer CenterDuarte, California  91010
CCOP - BeaumontRoyal Oak, Michigan  48073-6769
CCOP - Colorado Cancer Research Program, IncorporatedDenver, Colorado  80224
Hillman Cancer Center at University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15236
Markey Cancer Center at University of Kentucky Chandler Medical CenterLexington, Kentucky  40536-0084
Cancer Research Center at Boston Medical CenterBoston, Massachusetts  02118
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
St. Louis University Hospital Cancer CenterSaint Louis, Missouri  63110
Thompson Cancer Survival CenterKnoxville, Tennessee  37916
Comprehensive Cancer Centers of the DesertPalm Springs, California  92262
Catholic Healthcare West - Westbay RegionSan Francisco, California  94107-1728
North Idaho Cancer CenterCoeur d'Alene, Idaho  83814
Stanford Cancer Center at Stanford University Medical CenterStanford, California  94305
CCOP - Toledo Community HospitalToledo, Ohio  43623-3456
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Scripps Cancer Center at Scripps ClinicLa Jolla, California  92037
Lahey Clinic Medical Center - BurlingtonBurlington, Massachusetts  01805
Methodist Hospital Cancer Center at Nebraska Methodist Hospital - OmahaOmaha, Nebraska  68114-4199
Aultman Hospital Cancer Center at Aultman Health FoundationCanton, Ohio  44710-1799
Wellspan Health - York Cancer CenterYork, Pennsylvania  17403
CCOP - Marshfield Clinic Research FoundationMarshfield, Wisconsin  54449
Comprehensive Cancer InstituteHuntsville, Alabama  35801
MBCCOP - Howard University Cancer CenterWashington, District of Columbia  20060
Leo W. Jenkins Cancer Center of University Health Systems of Eastern CarolinaGreenville, North Carolina  27858-4354
Simmons Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390-9063
MBCCOP-Our Lady of Mercy Cancer CenterBronx, New York  10466
Charleston Area Medical CenterCharleston, West Virginia  25304
Creticos Cancer Center at Advocate Illinois Masonic Medical CenterChicago, Illinois  60657
John and Dorothy Morgan Cancer Center at Lehigh Valley HospitalAllentown, Pennsylvania  18105
Pacific Shores Medical GroupLong Beach, California  90813
Genesis Medical CenterDavenport, Iowa  52804
Providence Cancer Institute at Providence HospitalSouthfield, Michigan  48075
University of Connecticut Cancer Center at University of Connecticut Health CenterFarmington, Connecticut  06360-7106
Morton Plant HospitalClearwater, Florida  33756
University of Miami Sylvester Cancer CenterMiami, Florida  33136
John H. Stroger, Jr. Hospital of Cook CountyChicago, Illinois  60612-9985
Community HospitalMunster, Indiana  46321
Consultants in Blood Disorders and CancerLouisville, Kentucky  40207
Norton Healthcare Cancer CenterLouisville, Kentucky  40202-5070
Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New OrleansNew Orleans, Louisiana  70112
Tulane University Medical CenterNew Orleans, Louisiana  70112
New York Oncology Hematology, P.C. - Albany Regional Cancer CenterAlbany, New York  12208
Lincoln Medical and Mental Health CenterBronx, New York  10451
Charles R. Wood Foundation Cancer Center at Glens Falls HospitalGlens Falls, New York  12801
Alamance Cancer CenterBurlington, North Carolina  27216
Jewish Hospital of Cincinnati, IncorporatedCincinnati, Ohio  45236
South Pointe Hospital - Cancer Care CenterWarrensville Heights, Ohio  44122
Baptist Cancer Institute - Memphis at Baptist Memorial Hospital - MemphisMemphis, Tennessee  38146