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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004067
• Other study ID #: NSABP B-31
• Secondary ID: CDR0000067269
• Status: Completed
• Phase: Phase 3
• Start date: February 2000
• Est. completion date: November 2019

Study information

• Verified date: April 2021
• Source: NSABP Foundation Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2130
• Est. completion date: November 2019
• Est. primary completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• 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.

• 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.

Exclusion criteria

• 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.

• 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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• herceptin
4 mg/kg loading dose then 2 mg/kg weekly for 1 year.

Drug:
• adriamycin
60 mg/m2 IV push every 21 days for 4 cycles.
• cyclophosphamide
600 mg/m2 IV every 21 days for 4 cycles
• taxol
175 mg/m2 IV every 21 days for 4 cycles

Locations

Country	Name	City	State
Canada	Carlo Fidani Peel Regional Cancer Centre at 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-Sacrement, Quebec	Quebec City	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Akron City Hospital at Summa Health System	Akron	Ohio
United States	New York Oncology Hematology, P.C. at Albany Regional Cancer Care	Albany	New York
United States	Phoebe Cancer Center at Phoebe Putney Memorial Hospital	Albany	Georgia
United States	University of New Mexico Cancer Research and Treatment Center	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	MBCCOP-Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland
United States	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine
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	Vermont Cancer Center at University of Vermont	Burlington	Vermont
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	David Lee Cancer Center at 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 Cancer Institute at Rush University Medical Center	Chicago	Illinois
United States	Cancer Center at Jewish Hospital	Cincinnati	Ohio
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio
United States	South Pointe Hospital Cancer Care Center	Cleveland	Ohio
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 and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Genesis Regional Cancer Center at 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 Health System	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	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	CCOP - Grand Rapids	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	Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Helen and Harry Gray Cancer Center at 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	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Baptist 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	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 Comprehensive Hematology-Oncology Services - Long Beach	Long Beach	California
United States	Consultants in Blood Disorders and Cancer	Louisville	Kentucky
United States	Norton Cancer Center at Norton Hospital	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	University of Miami Sylvester Comprehensive 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	Oncology Alliance, S.C. - Milwaukee	Milwaukee	Wisconsin
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Community Hospital	Munster	Indiana
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	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 Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia
United States	West Suburban Hospital Medical Center	Oak Park	Illinois
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 Medical Center	Orange	California
United States	M.D. Anderson Cancer Center - Orlando	Orlando	Florida
United States	Comprehensive Cancer Center at Desert Regional Medical Center	Palm Springs	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	Cancer Research Network, Inc.	Plantation	Florida
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	William Beaumont Hospital - Royal Oak	Royal Oak	Michigan
United States	Sutter Cancer Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	Saint Louis University 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	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	Florida Cancer Specialists	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	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Nalitt Cancer Institute at 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 - Oklahoma	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	Warwick	Rhode Island
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	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts
United States	York Cancer Center at Wellspan Health	York	Pennsylvania
United States	Cancer Care Center at Northside Medical Center	Youngstown	Ohio

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (22)

Baselga J, Perez EA, Pienkowski T, Bell R. Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist. 2006;11 Suppl 1:4-12. Review. — View Citation

Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med. 2005 Oct 20;353(16):1652-4. — View Citation

Costa RB, Kurra G, Greenberg L, Geyer CE. Efficacy and cardiac safety of adjuvant trastuzumab-based chemotherapy regimens for HER2-positive early breast cancer. Ann Oncol. 2010 Nov;21(11):2153-2160. doi: 10.1093/annonc/mdq096. Epub 2010 Mar 29. Review. — View Citation

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. — View Citation

Garrison LP, Perez EA, Dueck A, et al.: Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2+ breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-6023, 306s, 2006.

Geyer CE Jr, Bryant J, Romond E: Cardiac safety analysis of the first stage of NSABP B-31, a randomized trial comparing the safety and efficacy of adriamycin® and cyclophosphamide (AC) followed by taxol® to that of AC followed by taxol® plus herceptin® in

Geyer CE, Bryant JL, Romond EH, et al.: Update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)?paclitaxel (T) vs. AC?T with trastuzumab (H). [Abstract] J Clin Oncol 24 (Suppl 18): A-581, 2006.

Gupta AK, Mekan SF, Eckman MH: Trastuzumab for all? A decision analysis examining tradeoffs between efficacy and cardiac toxicity of adjuvant therapy in HER2 positive breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-6022, 306s, 2006.

Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med. 2005 Oct 20;353(16):1734-6. — View Citation

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. Review. — View Citation

Kim C, Bryant J, Horne Z, et al.: Trastuzumab sensitivity of breast cancer with co-amplification of HER2 and cMYC suggests pro-apoptotic function of dysregulated cMYC in vivo. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-46, 2005.

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. — View Citation

Liberato NL, Marchetti M, Barosi G. Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2007 Feb 20;25(6):625-33. Erratum in: J Clin Oncol. 2007 Sep 1;25(25):4030. — View Citation

Paik S, Bryant J, Tan-Chiu E, Romond E, Hiller W, Park K, Brown A, Yothers G, Anderson S, Smith R, Wickerham DL, Wolmark N. Real-world performance of HER2 testing--National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst. 2002 Ju — View Citation

Perez E, Romond E, Suman V, et al.: Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patiens with HER2-positive breast cancer. [Abstract] J Clin Oncol 25 (Suppl 18): 512, 6s, 2007.

Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: j — View Citation

Rastogi P, Jeong J, Geyer CE, et al.: Five year update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)?paclitaxel (T) vs. AC?T with trastuzumab(H). [Abstract] J Clin Oncol 25 (Suppl 18): A-LBA513, 2

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.

Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klei — View Citation

Tan-Chiu E, Piccart M. Moving forward: Herceptin in the adjuvant setting. Oncology. 2002;63 Suppl 1:57-63. Review. — View Citation

Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, Shannon RP, Swain SM, Brown A, Fehrenbacher L, Vogel VG, Seay TE, Rastogi P, Mamounas EP, Wolmark N, Bryant J. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and — View Citation

Telli ML, Hunt SA, Carlson RW, Guardino AE. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol. 2007 Aug 10;25(23):3525-33. Review. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival (DFS)	Breast cancer recurrence, second primary cancer, death from any cause as first event	Time from randomization through 5 years
Primary	Cardiotoxicity		time from randomization through 4 months
Secondary	Survival	Death from any cause.	time from randomization through 5 years
Secondary	Long term effect of trastuzumab on cardiac function	Ejection fraction will be measured by multigated acquisition scan (MUGA).	At 5 and 10 years after randomization