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

• Sponsor: NSABP Foundation Inc (Other)
• Overall Status: Completed
• CT.gov ID: NCT00004067
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 2,130
• Locations: 149
• Arms: 2
• Duration (Months): 237
• Patients Per Site: 14.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: herceptin; Drug: adriamycin; Drug: cyclophosphamide; Drug: taxol	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Feb 1, 2000
• Actual Primary Completion Date: Mar 1, 2005
• Actual Study Completion Date: Nov 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1: adriamycin + cyclophosphamide then taxol	Drug: adriamycin; 60 mg/m2 IV push every 21 days for 4 cycles.; Other Names: doxorubicin ; Drug: cyclophosphamide; 600 mg/m2 IV every 21 days for 4 cycles; Drug: taxol; 175 mg/m2 IV every 21 days for 4 cycles; Other Names: paclitaxel
Experimental: Arm 2: adriamycin + cyclophosphamide then taxol + herceptin	Biological: herceptin; 4 mg/kg loading dose then 2 mg/kg weekly for 1 year.; Other Names: trastuzumab ; Drug: adriamycin; 60 mg/m2 IV push every 21 days for 4 cycles.; Other Names: doxorubicin ; Drug: cyclophosphamide; 600 mg/m2 IV every 21 days for 4 cycles; Drug: taxol; 175 mg/m2 IV every 21 days for 4 cycles; Other Names: paclitaxel

Outcome Measures

Primary Outcome Measures

1. Disease Free Survival (DFS) [Time from randomization through 5 years]

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

2. Cardiotoxicity [time from randomization through 4 months]

Secondary Outcome Measures

1. Survival [time from randomization through 5 years]

   Death from any cause.

2. Long term effect of trastuzumab on cardiac function [At 5 and 10 years after randomization]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Institute	Huntsville	Alabama	United States	35801
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99519-6604
3	CCOP - Western Regional, Arizona	Phoenix	Arizona	United States	85006-2726
4	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
5	Sutter Health Western Division Cancer Research Group	Greenbrae	California	United States	94904
6	Scripps Cancer Center at Scripps Clinic	La Jolla	California	United States	92037
7	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
8	Pacific Shores Medical Group Comprehensive Hematology-Oncology Services - Long Beach	Long Beach	California	United States	90813
9	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
10	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California	United States	92868
11	Comprehensive Cancer Center at Desert Regional Medical Center	Palm Springs	California	United States	92262
12	Sutter Cancer Center	Sacramento	California	United States	95816
13	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	San Diego	California	United States	92120
14	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
15	Kaiser Permanente Medical Center - Vallejo	Vallejo	California	United States	94589
16	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado	United States	80010
17	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado	United States	80209-5031
18	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut	United States	06360-7106
19	Helen and Harry Gray Cancer Center at Hartford Hospital	Hartford	Connecticut	United States	06102-5037
20	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
21	Morton Plant Hospital	Clearwater	Florida	United States	33756
22	Halifax Medical Center	Daytona Beach	Florida	United States	32114
23	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
24	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
25	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
26	M.D. Anderson Cancer Center - Orlando	Orlando	Florida	United States	32806
27	Cancer Research Network, Inc.	Plantation	Florida	United States	33324
28	Florida Cancer Specialists	Sarasota	Florida	United States	34236
29	Phoebe Cancer Center at Phoebe Putney Memorial Hospital	Albany	Georgia	United States	31701
30	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
31	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
32	MBCCOP-Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912-4000
33	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
34	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
35	North Idaho Cancer Center	Coeur d'Alene	Idaho	United States	83814
36	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612-9985
37	Rush Cancer Institute at Rush University Medical Center	Chicago	Illinois	United States	60612
38	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois	United States	60657
39	CCOP - Central Illinois	Decatur	Illinois	United States	62526
40	CCOP - Evanston	Evanston	Illinois	United States	60201
41	West Suburban Hospital Medical Center	Oak Park	Illinois	United States	60302
42	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61602
43	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
44	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana	United States	46206-1367
45	Community Hospital	Munster	Indiana	United States	46321
46	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
47	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa	United States	52803
48	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309-1016
49	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
50	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
51	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0093
52	Norton Cancer Center at Norton Hospital	Louisville	Kentucky	United States	40202-5070
53	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
54	Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans	New Orleans	Louisiana	United States	70112
55	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana	United States	70112
56	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
57	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine	United States	04401
58	Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
59	National Naval Medical Center	Bethesda	Maryland	United States	20889-5000
60	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
61	Berkshire Medical Center	Pittsfield	Massachusetts	United States	01201
62	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts	United States	01199
63	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts	United States	01655
64	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
65	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan	United States	48202
66	Michigan State University	East Lansing	Michigan	United States	48824
67	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
68	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
69	William Beaumont Hospital - Royal Oak	Royal Oak	Michigan	United States	48073
70	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan	United States	48075-9975
71	CCOP - Duluth	Duluth	Minnesota	United States	55805
72	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
73	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
74	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
75	CCOP - Kansas City	Kansas City	Missouri	United States	64131
76	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110-0250
77	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
78	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
79	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
80	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
81	Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska	United States	68114
82	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68131
83	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
84	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
85	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
86	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
87	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico	United States	87131
88	New York Oncology Hematology, P.C. at Albany Regional Cancer Care	Albany	New York	United States	12208
89	Lincoln Medical and Mental Health Center	Bronx	New York	United States	10451
90	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York	United States	10466
91	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York	United States	12801
92	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York	United States	10305
93	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13217
94	Alamance Cancer Center	Burlington	North Carolina	United States	27216
95	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
96	Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital	Greenville	North Carolina	United States	27858-4354
97	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
98	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
99	CCOP - Merit Care Hospital	Fargo	North Dakota	United States	58122
100	Akron City Hospital at Summa Health System	Akron	Ohio	United States	44309
101	Aultman Hospital Cancer Center at Aultman Health Foundation	Canton	Ohio	United States	44710
102	Cancer Center at Jewish Hospital	Cincinnati	Ohio	United States	45236
103	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267-0502
104	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio	United States	44106-5065
105	South Pointe Hospital Cancer Care Center	Cleveland	Ohio	United States	44122
106	CCOP - Columbus	Columbus	Ohio	United States	43206
107	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio	United States	43210-1240
108	CCOP - Dayton	Kettering	Ohio	United States	45429
109	Cancer Care Center at Northside Medical Center	Youngstown	Ohio	United States	44501
110	CCOP - Oklahoma	Tulsa	Oklahoma	United States	74136
111	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97213
112	John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18103
113	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
114	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
115	Albert Einstein Cancer Center	Philadelphia	Pennsylvania	United States	19141
116	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212-4772
117	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15213-3489
118	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
119	York Cancer Center at Wellspan Health	York	Pennsylvania	United States	17315
120	Kent County Memorial Hospital	Warwick	Rhode Island	United States	02886
121	CCOP - Greenville	Greenville	South Carolina	United States	29615
122	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
123	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota	United States	57104
124	Medical City Dallas Hospital	Dallas	Texas	United States	75230
125	Baylor College of Medicine	Houston	Texas	United States	77030
126	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410-1894
127	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
128	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
129	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
130	Vermont Cancer Center at University of Vermont	Burlington	Vermont	United States	05405-0075
131	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia	United States	23507
132	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037
133	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
134	Puget Sound Oncology Consortium	Seattle	Washington	United States	98109
135	CCOP - Northwest	Tacoma	Washington	United States	98405-0986
136	David Lee Cancer Center at Charleston Area Medical Center	Charleston	West Virginia	United States	25304-1297
137	Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26102
138	St. Vincent Hospital	Green Bay	Wisconsin	United States	54307-3508
139	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
140	Oncology Alliance, S.C. - Milwaukee	Milwaukee	Wisconsin	United States	53211-2906
141	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
142	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
143	Carlo Fidani Peel Regional Cancer Centre at Credit Valley Hospital	Mississauga	Ontario	Canada	L5M 2N1
144	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2L 4M1
145	Royal Victoria Hospital - Montreal	Montreal	Quebec	Canada	H3A 1A1
146	Montreal General Hospital	Montreal	Quebec	Canada	H3G 1A4
147	Jewish General Hospital - Montreal	Montreal	Quebec	Canada	H3T 1E2
148	St. Mary's Hospital Center	Montreal	Quebec	Canada	H3T 1M5
149	Hopital du Saint-Sacrement, Quebec	Quebec City	Quebec	Canada	G1S 4L8

Sponsors and Collaborators

• NSABP Foundation Inc
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Norman Wolmark, MD, NSABP Foundation Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med. 2005 Oct 20;353(16):1652-4.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
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• Responsible Party: NSABP Foundation Inc
• ClinicalTrials.gov Identifier: NCT00004067
• Other Study ID Numbers: NSABP B-31; CDR0000067269
• First Posted: Jan 27, 2003
• Last Update Posted: Apr 29, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by NSABP Foundation Inc: stage II breast cancer; stage IIIA breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Cyclophosphamide; Doxorubicin; Trastuzumab; Liposomal doxorubicin

Study Results

No Results Posted as of Apr 29, 2021