AzTrials
AzTrials

Breast CancerPhase 3NCT00004067

Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2

A Phase 3 study testing herceptin, adriamycin and cyclophosphamide in people with Breast Cancer, run by NSABP Foundation Inc at 149 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
herceptin, adriamycin and cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,130 participants
Where
149 sitesin 2 countries
Study dates
Feb 2000to Nov 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient must have a life expectancy of at least 10 years, excluding her diagnosis of breast cancer. (Comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer.)
  • The interval between the last surgery for breast cancer treatment (lumpectomy, mastectomy, axillary dissection, or re-excision of lumpectomy margins) and randomization must be less than or equal to 84 days.
  • All of the following staging criteria must be met:
  • Primary tumor must be T1-3 by clinical and pathologic evaluation.
  • Ipsilateral nodes must be cN0-1 by clinical evaluation.
  • Ipsilateral nodes must be pN1, pN2a, or pN3a by pathologic evaluation.
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  • M0
  • Patients must have undergone either a total mastectomy and an axillary dissection or a lumpectomy and an axillary dissection. Sentinel node biopsy is permitted, but must be followed by an axillary dissection.
  • The tumor must be invasive adenocarcinoma on histologic examination.
  • The tumor must be determined to be HER2-positive prior to randomization. Assays performed using fluorescent in situ hybridization (FISH) require gene amplification to be eligible. Assays using immunohistochemistry (IHC) must be performed at an NSABP-approved reference laboratory and require a strongly positive staining score.
  • Patients must have an analysis of both estrogen and progesterone receptors performed on the primary tumor prior to randomization. "Marginal," "borderline," etc., results (i.e., those not definitely negative) will also be considered positive regardless of the methodology used.
  • At the time of randomization, the patient must have had the following: history and physical exam, EKG, and PA and lateral chest x-ray within the past 3 months; and a bilateral mammogram (or unilateral if patient has had a mastectomy) and a pelvic exam (for women who have a uterus and who will be taking tamoxifen) within the past year.
  • Within 3 months prior to entry, the patient must have a baseline left ventricular ejection fraction (LVEF) measured by MUGA scan equal to or greater than the lower limit of normal for the radiology facility. (If LVEF is > 75%, the investigator should consider having the LVEF determination reviewed prior to randomization. Following randomization, the LVEF determination may be reviewed up until the time of the post-AC MUGA. Please note that if a more accurate value is obtained from the review of the baseline MUGA, the corrected value must be submitted to the NSABP Biostatistical Center before the post-AC MUGA is performed.)
  • At the time of randomization:
  • The postoperative absolute neutrophil count (ANC) must be ≥ 1500/mm3 (or <1500/mm3 if, in the opinion of the investigator, this represents an ethnic or racial variation of normal).
  • Postoperative platelet count must be ≥ 100,000/mm3. Significant underlying hematologic disorders must be excluded when the platelet count is above the upper limit of normal for the lab.
  • There must be postoperative evidence of adequate hepatic function, i.e., total bilirubin must be ≤ ULN for the lab unless the patient has a chronic grade 1 bilirubin elevation (>ULN to ≤1.5 x ULN) due to Gilbert's disease or similar syndrome; and alkaline phosphatase must be <2.5 times the ULN for the lab; and the serum glutamic-oxaloacetic transaminase (SGOT [AST]) must be <1.5 times the ULN for the lab.
  • There must be postoperative evidence of adequate renal function (serum creatinine within or less than the institution's normal range).
  • Patients must have no clinical or radiologic evidence of metastatic disease. Suspicious findings must be confirmed as benign by radiologic evaluation or biopsy. A patient with skeletal pain is eligible for inclusion in the study if bone scan and/or roentgenological examination fails to disclose metastatic disease.
  • Patients with a history of non-breast malignancies are eligible if they have been disease-free for 5 or more years prior to randomization and are deemed by their physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Prior to randomization, the investigator must designate whether the patients who had a lumpectomy will receive local or locoregional radiation therapy. For patients who had a mastectomy, the investigator must designate whether or not the patient will receive radiation therapy. (Pre-randomization discussion and/or consultation with a radiation oncologist is encouraged.) Note: Irradiation of any internal mammary nodes is prohibited in this trial.
  • Special conditions for eligibility of lumpectomy patients: irradiation and surgery
  • Patients treated by lumpectomy and axillary node dissection to be followed by breast radiation therapy must meet all the eligibility criteria in addition to the following: Generally, lumpectomy should be reserved for tumors <5 cm. However, at the investigator's discretion, patients treated with lumpectomy for tumors ≥ 5 cm are eligible. The margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist. In patients in whom pathologic examination demonstrates tumor present at the line of resection, additional operative procedures may be performed to obtain clear margins. This is permissible even if axillary dissection has been performed. Patients in whom tumor is still present at the resected margin after re-excision(s) must undergo total mastectomy to be eligible. Whole breast irradiation is required. Irradiation of regional lymph nodes is optional, but partial breast irradiation and irradiation of any internal mammary nodes are prohibited in this trial. Intent to irradiate the axilla or other regional node groups must be declared by the investigator prior to randomization for stratification purposes.
  • Special conditions for eligibility of mastectomy patients: irradiation. The decision to use locoregional irradiation in patients who have undergone total mastectomy and axillary node dissection must be declared by the investigator prior to randomization for stratification purposes. Failure to adhere to the radiation therapy plan will be a protocol violation.

Who cannot join

  • Bilateral malignancy or a mass or mammographic abnormality in the opposite breast suspicious for malignancy unless there is biopsy proof that the mass is not malignant.
  • Primary tumor staged as T4 for any reason.
  • Nodes staged as clinical N2 or N3 for any reason and nodes staged as pathologic pN2b, pN3b, or pN3c.
  • Prior history of breast cancer, including DCIS (patients with a history of lobular carcinoma in situ [LCIS] are eligible).
  • Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to randomization. The only exception is hormonal therapy, which may have been given for up to a total of 28 days anytime after diagnosis and before randomization. In such a case, hormonal therapy must stop at or before randomization and be re-started if indicated following chemotherapy.
  • Prior anthracycline or taxane therapy for any malignancy.
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  • Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible only if this therapy is discontinued prior to randomization.)
  • Therapy with any hormonal agents such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention. (Patients are eligible only if these medications are discontinued prior to randomization. These medications are not permitted while on the study except for the use of tamoxifen as described in the protocol)
  • Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude a patient from being subjected to any of the treatment options or would prevent prolonged follow-up.
  • Cardiac disease that would preclude the use of Adriamycin, Taxol or Herceptin. This includes:
  • Active cardiac disease:
  • angina pectoris that requires the use of antianginal medication;
  • cardiac arrhythmia requiring medication;
  • severe conduction abnormality;
  • clinically significant valvular disease;
  • cardiomegaly on chest x-ray;
  • ventricular hypertrophy on EKG; or
  • patients with poorly controlled hypertension, i.e., diastolic greater than 100 mm/Hg. (Patients with hypertension who are well controlled on medication are eligible for entry.)
  • History of cardiac disease:
  • myocardial infarction documented as a clinical diagnosis or by EKG or any other tests;
  • documented congestive heart failure; or
  • documented cardiomyopathy.
  • Psychiatric or addictive disorders that would preclude obtaining informed consent.
  • Pregnancy or lactation at the time of proposed randomization. This protocol excludes pregnant or lactating women based on the fetal toxicity of both tamoxifen and Taxol which are listed as Pregnancy Category D agents. Pregnant women who received tamoxifen have experienced fetal deaths, birth defects, spontaneous abortions, and vaginal bleeding. Women of reproductive potential must agree to use an effective barrier method of contraception. Hormonal birth control methods are not permitted.
  • Sensory/motor neuropathy ≥ grade 2, as defined by the NCI's Common Toxicity Criteria version 2.0.
  • Contraindications to corticosteroid use which, in the opinion of the investigator, would preclude participation in this study.
  • Concurrent treatment with other investigational agents.
  • Sensitivity to benzyl alcohol.
  • Special conditions for ineligibility of lumpectomy patients: irradiation and surgery. For patients treated by lumpectomy with axillary dissection, breast irradiation is required. Please see guidelines for radiation therapy in Appendix A. In addition, the following patients will also be ineligible:
  • Patients with diffuse tumors (as demonstrated on mammography) that would not be considered surgically amenable to lumpectomy.
  • Patients treated with lumpectomy in whom there is another clinically dominant mass or mammographically suspicious abnormality within the ipsilateral breast remnant. Such a mass must be biopsied and demonstrated to be histologically benign prior to randomization or, if malignant, must be surgically removed with clear margins.
  • Patients in whom the margins of the resected specimen are involved with invasive tumor or ductal carcinoma in situ (DCIS). Additional surgical resections to obtain free margins are allowed. Patients in whom tumor is still present after the additional resection(s) must undergo mastectomy to be eligible.

Trial locations and contacts

149 sites in 2 countries.

149 sites in 2 countries

United States141 sites

  • Akron City Hospital at Summa Health System

    Akron, Ohio, 44309

  • Phoebe Cancer Center at Phoebe Putney Memorial Hospital

    Albany, Georgia, 31701

  • New York Oncology Hematology, P.C. at Albany Regional Cancer Care

    Albany, New York, 12208

  • University of New Mexico Cancer Research and Treatment Center

    Albuquerque, New Mexico, 87131

  • John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital

    Allentown, Pennsylvania, 18103

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99519-6604

  • CCOP - Michigan Cancer Research Consortium

    Ann Arbor, Michigan, 48106

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • CCOP - Atlanta Regional

    Atlanta, Georgia, 30342-1701

  • MBCCOP-Medical College of Georgia Cancer Center

    Augusta, Georgia, 30912-4000

  • Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center

    Baltimore, Maryland, 21237

  • CancerCare of Maine at Eastern Maine Medial Center

    Bangor, Maine, 04401

  • National Naval Medical Center

    Bethesda, Maryland, 20889-5000

  • CCOP - Montana Cancer Consortium

    Billings, Montana, 59101

  • Cancer Research Center at Boston Medical Center

    Boston, Massachusetts, 02118

  • Alamance Cancer Center

    Burlington, North Carolina, 27216

  • Vermont Cancer Center at University of Vermont

    Burlington, Vermont, 05405-0075

  • Aultman Hospital Cancer Center at Aultman Health Foundation

    Canton, Ohio, 44710

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

  • David Lee Cancer Center at Charleston Area Medical Center

    Charleston, West Virginia, 25304-1297

  • John H. Stroger, Jr. Hospital of Cook County

    Chicago, Illinois, 60612-9985

  • Rush Cancer Institute at Rush University Medical Center

    Chicago, Illinois, 60612

  • Creticos Cancer Center at Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Cancer Center at Jewish Hospital

    Cincinnati, Ohio, 45236

  • Charles M. Barrett Cancer Center at University Hospital

    Cincinnati, Ohio, 45267-0502

  • Morton Plant Hospital

    Clearwater, Florida, 33756

  • Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University

    Cleveland, Ohio, 44106-5065

  • South Pointe Hospital Cancer Care Center

    Cleveland, Ohio, 44122

  • North Idaho Cancer Center

    Coeur d'Alene, Idaho, 83814

  • Ellis Fischel Cancer Center at University of Missouri - Columbia

    Columbia, Missouri, 65203

  • CCOP - Columbus

    Columbus, Ohio, 43206

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

    Columbus, Ohio, 43210-1240

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822-2001

  • Genesis Regional Cancer Center at Genesis Medical Center

    Davenport, Iowa, 52803

  • Halifax Medical Center

    Daytona Beach, Florida, 32114

  • CCOP - Central Illinois

    Decatur, Illinois, 62526

  • University of Colorado Cancer Center at University of Colorado Health Sciences Center

    Denver, Colorado, 80010

  • CCOP - Colorado Cancer Research Program, Incorporated

    Denver, Colorado, 80209-5031

  • CCOP - Iowa Oncology Research Association

    Des Moines, Iowa, 50309-1016

  • Josephine Ford Cancer Center at Henry Ford Health System

    Detroit, Michigan, 48202

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • CCOP - Duluth

    Duluth, Minnesota, 55805

  • Michigan State University

    East Lansing, Michigan, 48824

  • CCOP - Evanston

    Evanston, Illinois, 60201

  • CCOP - Merit Care Hospital

    Fargo, North Dakota, 58122

  • Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

    Farmington, Connecticut, 06360-7106

  • Dwight David Eisenhower Army Medical Center

    Fort Gordon, Georgia, 30905-5650

  • Charles R. Wood Cancer Center at Glens Falls Hospital

    Glens Falls, New York, 12801

  • CCOP - Grand Rapids

    Grand Rapids, Michigan, 49503

  • St. Vincent Hospital

    Green Bay, Wisconsin, 54307-3508

  • Sutter Health Western Division Cancer Research Group

    Greenbrae, California, 94904

  • Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital

    Greenville, North Carolina, 27858-4354

  • CCOP - Greenville

    Greenville, South Carolina, 29615

  • CCOP - Northern New Jersey

    Hackensack, New Jersey, 07601

  • Helen and Harry Gray Cancer Center at Hartford Hospital

    Hartford, Connecticut, 06102-5037

  • Cancer Research Center of Hawaii

    Honolulu, Hawaii, 96813

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Comprehensive Cancer Institute

    Huntsville, Alabama, 35801

  • Methodist Cancer Center at Methodist Hospital

    Indianapolis, Indiana, 46206-1367

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1009

  • Baptist Cancer Institute - Jacksonville

    Jacksonville, Florida, 32207

  • CCOP - Kalamazoo

    Kalamazoo, Michigan, 49007-3731

  • CCOP - Kansas City

    Kansas City, Missouri, 64131

  • CCOP - Dayton

    Kettering, Ohio, 45429

  • Scripps Cancer Center at Scripps Clinic

    La Jolla, California, 92037

  • CCOP - Southern Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89106

  • Markey Cancer Center at University of Kentucky Chandler Medical Center

    Lexington, Kentucky, 40536-0093

  • Loma Linda University Cancer Institute at Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Pacific Shores Medical Group Comprehensive Hematology-Oncology Services - Long Beach

    Long Beach, California, 90813

  • Norton Cancer Center at Norton Hospital

    Louisville, Kentucky, 40202-5070

  • Consultants in Blood Disorders and Cancer

    Louisville, Kentucky, 40207

  • Joe Arrington Cancer Research and Treatment Center

    Lubbock, Texas, 79410-1894

  • CCOP - Marshfield Clinic Research Foundation

    Marshfield, Wisconsin, 54449

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • CCOP - Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Oncology Alliance, S.C. - Milwaukee

    Milwaukee, Wisconsin, 53211-2906

  • Medical College of Wisconsin Cancer Center

    Milwaukee, Wisconsin, 53226

  • Hennepin County Medical Center - Minneapolis

    Minneapolis, Minnesota, 55415

  • Community Hospital

    Munster, Indiana, 46321

  • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08903

  • Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans

    New Orleans, Louisiana, 70112

  • Tulane Cancer Center at Tulane University Hospital and Clinic

    New Orleans, Louisiana, 70112

  • CCOP - Ochsner

    New Orleans, Louisiana, 70121

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Sentara Cancer Institute at Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • West Suburban Hospital Medical Center

    Oak Park, Illinois, 60302

  • CCOP - Bay Area Tumor Institute

    Oakland, California, 94609-3305

  • Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha

    Omaha, Nebraska, 68114

  • CCOP - Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68131

  • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

    Orange, California, 92868

  • M.D. Anderson Cancer Center - Orlando

    Orlando, Florida, 32806

  • Comprehensive Cancer Center at Desert Regional Medical Center

    Palm Springs, California, 92262

  • Camden-Clark Memorial Hospital

    Parkersburg, West Virginia, 26102

  • CCOP - Illinois Oncology Research Association

    Peoria, Illinois, 61602

  • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

    Philadelphia, Pennsylvania, 19107-5541

  • Albert Einstein Cancer Center

    Philadelphia, Pennsylvania, 19141

  • CCOP - Western Regional, Arizona

    Phoenix, Arizona, 85006-2726

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212-4772

  • Hillman Cancer Center at University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15213-3489

  • Berkshire Medical Center

    Pittsfield, Massachusetts, 01201

  • Cancer Research Network, Inc.

    Plantation, Florida, 33324

  • CCOP - Columbia River Oncology Program

    Portland, Oregon, 97213

  • Utah Valley Regional Medical Center - Provo

    Provo, Utah, 84604

  • MBCCOP - Massey Cancer Center

    Richmond, Virginia, 23298-0037

  • William Beaumont Hospital - Royal Oak

    Royal Oak, Michigan, 48073

  • Sutter Cancer Center

    Sacramento, California, 95816

  • CCOP - Metro-Minnesota

    Saint Louis Park, Minnesota, 55416

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78284-7811

  • Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego

    San Diego, California, 92120

  • CCOP - Santa Rosa Memorial Hospital

    Santa Rosa, California, 95403

  • Florida Cancer Specialists

    Sarasota, Florida, 34236

  • Mercy Hospital Cancer Center - Scranton

    Scranton, Pennsylvania, 18501

  • CCOP - Virginia Mason Research Center

    Seattle, Washington, 98101

  • Puget Sound Oncology Consortium

    Seattle, Washington, 98109

  • CCOP - Sioux Community Cancer Consortium

    Sioux Falls, South Dakota, 57104

  • CCOP - Northern Indiana CR Consortium

    South Bend, Indiana, 46601

  • Providence Cancer Institute at Providence Hospital - Southfield Campus

    Southfield, Michigan, 48075-9975

  • CCOP - Upstate Carolina

    Spartanburg, South Carolina, 29303

  • Baystate Regional Cancer Program at D'Amour Center for Cancer Care

    Springfield, Massachusetts, 01199

  • CCOP - Cancer Research for the Ozarks

    Springfield, Missouri, 65807

  • Saint Louis University Cancer Center

    St Louis, Missouri, 63110-0250

  • Missouri Baptist Cancer Center

    St Louis, Missouri, 63131

  • CCOP - St. Louis-Cape Girardeau

    St Louis, Missouri, 63141

  • Nalitt Cancer Institute at Staten Island University Hospital

    Staten Island, New York, 10305

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

    Syracuse, New York, 13217

  • CCOP - Northwest

    Tacoma, Washington, 98405-0986

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • Lincoln Medical and Mental Health Center

    The Bronx, New York, 10451

  • MBCCOP-Our Lady of Mercy Cancer Center

    The Bronx, New York, 10466

  • CCOP - Oklahoma

    Tulsa, Oklahoma, 74136

  • CCOP - Carle Cancer Center

    Urbana, Illinois, 61801

  • Kaiser Permanente Medical Center - Vallejo

    Vallejo, California, 94589

  • Kent County Memorial Hospital

    Warwick, Rhode Island, 02886

  • CCOP - Wichita

    Wichita, Kansas, 67214-3882

  • CCOP - Christiana Care Health Services

    Wilmington, Delaware, 19899

  • CCOP - Southeast Cancer Control Consortium

    Winston-Salem, North Carolina, 27104-4241

  • Comprehensive Cancer Center at Wake Forest University

    Winston-Salem, North Carolina, 27157-1082

  • UMASS Memorial Cancer Center - University Campus

    Worcester, Massachusetts, 01655

  • York Cancer Center at Wellspan Health

    York, Pennsylvania, 17315

  • Cancer Care Center at Northside Medical Center

    Youngstown, Ohio, 44501

Other trials in United States

Canada8 sites

  • Carlo Fidani Peel Regional Cancer Centre at Credit Valley Hospital

    Mississauga, Ontario, L5M 2N1

  • Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec, H2L 4M1

  • Royal Victoria Hospital - Montreal

    Montreal, Quebec, H3A 1A1

  • Montreal General Hospital

    Montreal, Quebec, H3G 1A4

  • Jewish General Hospital - Montreal

    Montreal, Quebec, H3T 1E2

  • St. Mary's Hospital Center

    Montreal, Quebec, H3T 1M5

  • Hopital du Saint-Sacrement, Quebec

    Québec, Quebec, G1S 4L8

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Randomized Trial Comparing the Safety and Efficacy of Adriamycin and Cyclophosphamide Followed by Taxol (AC-T) to That of Adriamycin and Cyclophosphamide Followed by Taxol Plus Herceptin (AC-T+H) in Node-Positive Breast Cancer Patients Who Have Tumors That Overexpress HER2

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy plus trastuzumab is more effective than combination chemotherapy alone for treating breast cancer.

PURPOSE: This randomized phase III trial is studying how well giving combination chemotherapy together with trastuzumab works compared to combination chemotherapy alone in treating women with node-positive stage II or stage IIIA breast cancer that overexpresses HER2.

Read the detailed description

OBJECTIVES:

  • Compare the cardiotoxicity of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab (Herceptin®) in women with operable, node-positive breast cancer that overexpresses HER2.
  • Compare the effect of these regimens on disease-free and overall survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (1-3 vs 4-9 vs 10 or more), administration of hormonal therapy (tamoxifen vs anastrozole vs neither), surgery/radiotherapy (lumpectomy plus breast irradiation vs lumpectomy plus breast irradiation plus regional irradiation vs mastectomy without radiotherapy vs mastectomy with radiotherapy), paclitaxel schedule (every 3 weeks vs weekly), and participating center. Patients are randomized to one of two treatment arms.

  • Arm 1: Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses. Approximately 3 weeks after the last course, patients receive paclitaxel IV over 3 hours every 21 days for 4 courses OR paclitaxel IV over 1 hour once weekly for 12 weeks (12 doses).
  • Arm 2: Patients receive chemotherapy as in arm I and trastuzumab (Herceptin®) IV over 90 minutes on day 1 of the first course of paclitaxel. Trastuzumab is then administered IV over 30 minutes weekly for 51 weeks, beginning on day 8.

All patients with estrogen or progesterone receptor-positive tumors receive hormonal therapy* for at least 5 years, beginning within 3-12 weeks after the last dose of chemotherapy. Patients who have received prior tamoxifen for prevention may be treated with additional tamoxifen for no more than 5 years at the discretion of the principal investigator (PI).

NOTE: *Other hormonal therapeutic agents are allowed in sequence with or as an alternative to tamoxifen therapy.

All patients previously treated with lumpectomy undergo breast irradiation beginning after completion of chemotherapy and concurrently with trastuzumab (in arm 2) administration. Patients previously treated with mastectomy may also receive radiotherapy. Radiotherapy is administered daily for 5-6 weeks.

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

PROJECTED ACCRUAL: A total of 2,700 patients will be accrued for this study within 4.75 years.

Conditions
Breast Cancer
Being tested
herceptin, adriamycin, cyclophosphamide, taxol
Keywords
stage II breast cancer, stage IIIA breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • herceptinBiological

    Also called trastuzumab

    4 mg/kg loading dose then 2 mg/kg weekly for 1 year.

  • adriamycinDrug

    Also called doxorubicin

    60 mg/m2 IV push every 21 days for 4 cycles.

  • cyclophosphamideDrug

    600 mg/m2 IV every 21 days for 4 cycles

  • taxolDrug

    Also called paclitaxel

    175 mg/m2 IV every 21 days for 4 cycles

Study groups in NCT00004067
Study groupRoleWhat they receive
Arm 1: adriamycin + cyclophosphamide then taxolActive comparatorNot described
Receives: Drug: adriamycin; Drug: cyclophosphamide; Drug: taxol
Arm 2: adriamycin + cyclophosphamide then taxol + herceptinExperimentalNot described
Receives: Biological: herceptin; Drug: adriamycin; Drug: cyclophosphamide; Drug: taxol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Free Survival (DFS)

    Breast cancer recurrence, second primary cancer, death from any cause as first event

    Measured: Time from randomization through 5 years

  2. Cardiotoxicity

    Measured: time from randomization through 4 months

Secondary outcomes (2)

  1. Survival

    Death from any cause.

    Measured: time from randomization through 5 years

  2. Long term effect of trastuzumab on cardiac function

    Ejection fraction will be measured by multigated acquisition scan (MUGA).

    Measured: At 5 and 10 years after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startFeb 2000
  3. Primary completionMar 2005
  4. Study completionNov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2,130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004067
Sponsor's protocol ID
NSABP B-31
Other IDs
CDR0000067269
Status last verified
Apr 2021
First submitted
10 Dec 1999
Last updated
29 Apr 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Jahanzeb M. Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer. 2008 Aug;8(4):324-33. doi: 10.3816/CBC.2008.n.037.

    PubMed 18757259

  • Reinholz MM, Dueck AC, Lingle WL, et al.: The concordance between NCCTG's and NSABP's C-myc FISH assays. [Abstract] J Clin Oncol 26 (Suppl 15): A-22110, 2008.

  • Garrison LP Jr, Lubeck D, Lalla D, Paton V, Dueck A, Perez EA. Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Cancer. 2007 Aug 1;110(3):489-98. doi: 10.1002/cncr.22806.

    PubMed 17592827

  • Kurian AW, Thompson RN, Gaw AF, Arai S, Ortiz R, Garber AM. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol. 2007 Feb 20;25(6):634-41. doi: 10.1200/JCO.2006.06.3081.

    PubMed 17308268

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing herceptin, adriamycin and cyclophosphamide in people with Breast Cancer, run by NSABP Foundation Inc at 149 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 149 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (DFS) (time frame: Time from randomization through 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004067, which also lists 28 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2021.

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