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

• Sponsor: NSABP Foundation Inc (Other)
• Overall Status: Completed
• CT.gov ID: NCT00003782
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 5,351
• Locations: 157
• Arms: 3
• Duration (Months): 165.1
• Patients Per Site: 34.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy after surgery may kill any tumor cells remaining following surgery. It is not yet known which regimen of combination chemotherapy is more effective in treating breast cancer with positive axillary lymph nodes.

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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: cyclophosphamide; Drug: docetaxel; Drug: doxorubicin	Phase 3

Detailed Description

OBJECTIVES:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 5351 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Three-Arm Randomized Trial to Compare Adjuvant Adriamycin and Cyclophosphamide Followed by Taxotere (AC-T); Adriamycin and Taxotere (AT); and Adriamycin, Taxotere, and Cyclophosphamide (ATC) in Breast Cancer Patients With Positive Axillary Lymph Nodes
• Study Start Date: Mar 1, 1999
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Doxorubicin + Cyclophosphamide, then Docetaxel Doxorubicin + Cyclophosphamide, then Docetaxel	Drug: cyclophosphamide; Arm 1: 600 mg/m2 IV every 21 days for 4 cycles; Arm 3: 500 mg/m2 IV every 21 days for 4 cycles; Drug: docetaxel; Arm 1: 100 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 75 mg/m2 IV every 21 days for 4 cycles; Other Names: Taxotere ; Drug: doxorubicin; Arm 1: 60 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 50 mg/m2 IV every 21 days for 4 cycles; Other Names: Adriamycin
Experimental: Arm 2: Doxorubicin + Docetaxel Doxorubicin + Docetaxel	Drug: docetaxel; Arm 1: 100 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 75 mg/m2 IV every 21 days for 4 cycles; Other Names: Taxotere ; Drug: doxorubicin; Arm 1: 60 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 50 mg/m2 IV every 21 days for 4 cycles; Other Names: Adriamycin
Experimental: Arm 3: Doxorubicin + Docetaxel + Cyclophosphamide Doxorubicin + Docetaxel + Cyclophosphamide	Drug: cyclophosphamide; Arm 1: 600 mg/m2 IV every 21 days for 4 cycles; Arm 3: 500 mg/m2 IV every 21 days for 4 cycles; Drug: docetaxel; Arm 1: 100 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 75 mg/m2 IV every 21 days for 4 cycles; Other Names: Taxotere ; Drug: doxorubicin; Arm 1: 60 mg/m2 IV every 21 days for 4 cycles; Arms 2 and 3: 50 mg/m2 IV every 21 days for 4 cycles; Other Names: Adriamycin

Outcome Measures

Primary Outcome Measures

1. Overall Survival [8 years]

2. Disease Free Survival [time to event: breast cancer recurrence; second primary cancer; death from any cause as a first event]

Secondary Outcome Measures

1. Toxicities Among the 3 Regimens [9 years]

2. Quality of Life Among Breast Cancer Patients [baseline, 9 weeks, and 6, 12, 18, and 24 months]

3. Amenorrhea in Premenopausal Women [baseline, 9 weeks, and 6, 12, 18, and 24 months]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive adenocarcinoma of the breast

• Confined to the breast and ipsilateral axilla on clinical exam

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

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

• Sentinel node biopsy allowed if followed by axillary dissection

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

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

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

• Prior lumpectomy and axillary dissection

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

• Margins must be clear

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

• No histologically evident invasive tumor or ductal carcinoma in situ

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

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

• Histologically benign

• Surgically removed with clear margins if malignant

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

• Tethering or dimpling of the skin or nipple inversion allowed

• No metastatic disease

• Skeletal pain allowed if bone scan negative for metastases

• Hormone receptor status:

• Estrogen and progesterone status determined

PATIENT CHARACTERISTICS:

Age:

• greater than or equal to 18 years

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• At least 10 years, excluding diagnosis of cancer

Hematopoietic:

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

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

Hepatic:

• Bilirubin no greater than ULN

• Alkaline phosphatase less than 2.5 times ULN*

• SGOT less than 1.5 times ULN*

• No nonmalignant systemic hepatic disease that would preclude study participation NOTE: *Alkaline phosphatase and SGOT cannot both be greater than ULN

Renal:

• Creatinine no greater than normal

• No nonmalignant systemic renal disease that would preclude study participation

Cardiovascular:

• No nonmalignant systemic cardiovascular disease that would preclude study participation

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

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

• Any prior myocardial infarction

• Angina pectoris requiring anti-anginal medication

• History of congestive heart failure

• Cardiac arrhythmia requiring medication

• Severe conduction abnormality

• Valvular disease with documented cardiac function compromise

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

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

• Hypertension well controlled by medication allowed

Other:

• No grade 2 or greater peripheral neuropathy

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

• Effectively treated squamous cell or basal cell skin cancer

• Surgically treated carcinoma in situ of the cervix

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

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• No nonmalignant systemic disease that would preclude study participation

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

• No psychiatric or addictive disorders that would preclude informed consent

• No contraindication to corticosteroids that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy for breast cancer

Chemotherapy:

• No prior chemotherapy for breast cancer

• No prior anthracyclines or taxanes

• No other concurrent investigational chemotherapy

Endocrine therapy:

• No prior hormonal therapy for breast cancer

• No concurrent hormonal birth control methods or other hormonal therapy

• No concurrent raloxifene, including for osteoporosis

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

Radiotherapy:

• See Disease Characteristics

• No prior radiotherapy for this malignancy

Surgery:

• See Disease Characteristics

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

Other:

• No prior systemic therapy for this malignancy

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

• Concurrent bisphosphonates allowed

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	California Cancer Center	Fresno	California	United States	93720
6	Sutter Health Western Division Cancer Research Group	Greenbrae	California	United States	94904
7	Scripps Cancer Center at Scripps Clinic	La Jolla	California	United States	92037
8	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
9	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
10	Pacific Shores Medical Group	Long Beach	California	United States	90813
11	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
12	Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center	Orange	California	United States	92868
13	Comprehensive Cancer Centers of the Desert	Palm Springs	California	United States	92262
14	Stanford Cancer Center at Stanford University Medical Center	Palo Alto	California	United States	94305-5408
15	Sutter Cancer Center	Sacramento	California	United States	95816
16	Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego	San Diego	California	United States	92120
17	Catholic Healthcare West - Westbay Region	San Francisco	California	United States	94107-1728
18	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
19	Kaiser Permanente Medical Center - Vallejo	Vallejo	California	United States	94589
20	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado	United States	80010
21	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado	United States	80209-5031
22	University of Connecticut Cancer Center at University of Connecticut Health Center	Farmington	Connecticut	United States	06360-7106
23	Hartford Hospital	Hartford	Connecticut	United States	06102-5037
24	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
25	MBCCOP - Howard University Cancer Center	Washington	District of Columbia	United States	20060
26	Morton Plant Hospital	Clearwater	Florida	United States	33756
27	Halifax Medical Center	Daytona Beach	Florida	United States	32114
28	Baptist Regional Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
29	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
30	University of Miami Sylvester Cancer Center	Miami	Florida	United States	33136
31	MD Anderson Cancer Center Orlando	Orlando	Florida	United States	32806
32	Sarasota Memorial Hospital	Sarasota	Florida	United States	34239
33	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
34	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
35	Medical College of Georgia Comprehensive Cancer Center	Augusta	Georgia	United States	30912-4000
36	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
37	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
38	North Idaho Cancer Center	Coeur d'Alene	Idaho	United States	83814
39	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612-9985
40	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois	United States	60612
41	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois	United States	60657
42	CCOP - Central Illinois	Decatur	Illinois	United States	62526
43	CCOP - Evanston	Evanston	Illinois	United States	60201
44	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61602
45	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
46	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana	United States	46206-1367
47	St. Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
48	Community Hospital	Munster	Indiana	United States	46321
49	Genesis Medical Center	Davenport	Iowa	United States	52804
50	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309-1016
51	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
52	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
53	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0093
54	Norton Healthcare Cancer Center	Louisville	Kentucky	United States	40202-5070
55	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
56	Stanley S. Scott Cancer Center at Louisiana State University Medical Center - New Orleans	New Orleans	Louisiana	United States	70112
57	Tulane University Medical Center	New Orleans	Louisiana	United States	70112
58	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
59	Eastern Maine Medical Center	Bangor	Maine	United States	04401
60	Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
61	National Naval Medical Center	Bethesda	Maryland	United States	20889-5000
62	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
63	Lahey Clinic Medical Center - Burlington	Burlington	Massachusetts	United States	01805
64	Berkshire Medical Center	Pittsfield	Massachusetts	United States	01201
65	Baystate Medical Center	Springfield	Massachusetts	United States	01199
66	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
67	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
68	Michigan State University	East Lansing	Michigan	United States	48824
69	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
70	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
71	CCOP - Beaumont	Royal Oak	Michigan	United States	48073-6769
72	Providence Cancer Institute at Providence Hospital	Southfield	Michigan	United States	48075-9975
73	CCOP - Duluth	Duluth	Minnesota	United States	55805
74	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
75	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
76	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
77	CCOP - Kansas City	Kansas City	Missouri	United States	64131
78	St. Louis University Hospital Cancer Center	Saint Louis	Missouri	United States	63110-0250
79	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
80	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
81	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
82	Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha	Omaha	Nebraska	United States	68114
83	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68131
84	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
85	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
86	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
87	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
88	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico	United States	87131
89	New York Oncology Hematology, P.C. - Albany Regional Cancer Center	Albany	New York	United States	12208
90	Lincoln Medical and Mental Health Center	Bronx	New York	United States	10451
91	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York	United States	10466
92	Charles R. Wood Foundation Cancer Center at Glens Falls Hospital	Glens Falls	New York	United States	12801
93	Staten Island University Hospital	Staten Island	New York	United States	10305
94	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13217
95	Alamance Cancer Center	Burlington	North Carolina	United States	27216
96	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
97	Leo W. Jenkins Cancer Center of University Health Systems of Eastern Carolina	Greenville	North Carolina	United States	27858-4354
98	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
99	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
100	CCOP - Merit Care Hospital	Fargo	North Dakota	United States	58122
101	Akron City Hospital	Akron	Ohio	United States	44309
102	Aultman Hospital Cancer Center at Aultman Health Foundation	Canton	Ohio	United States	44710
103	Jewish Hospital of Cincinnati, Incorporated	Cincinnati	Ohio	United States	45236
104	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267-0502
105	CCOP - Columbus	Columbus	Ohio	United States	43206
106	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210-1240
107	CCOP - Dayton	Kettering	Ohio	United States	45429
108	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43623-3456
109	South Pointe Hospital - Cancer Care Center	Warrensville Heights	Ohio	United States	44122
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	Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
119	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
120	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
121	Wellspan Health - York Cancer Center	York	Pennsylvania	United States	17315
122	CCOP - Greenville	Greenville	South Carolina	United States	29615
123	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
124	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
125	Baptist Cancer Institute - Memphis at Baptist Memorial Hospital - Memphis	Memphis	Tennessee	United States	38146
126	Medical City Dallas Hospital	Dallas	Texas	United States	75230
127	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75235-9154
128	Baylor College of Medicine	Houston	Texas	United States	77030
129	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410-1894
130	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
131	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
132	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
133	Green Mountain Oncology Group	Bennington	Vermont	United States	05201
134	Virginia Oncology Associates - Newport News	Newport News	Virginia	United States	23606
135	Eastern Virginia Medical School	Norfolk	Virginia	United States	23507
136	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037
137	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia	United States	24014
138	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
139	Puget Sound Oncology Consortium	Seattle	Washington	United States	98109
140	CCOP - Northwest	Tacoma	Washington	United States	98405-0986
141	Charleston Area Medical Center	Charleston	West Virginia	United States	25304-1297
142	Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26102
143	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin	United States	54301
144	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
145	St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
146	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
147	Tom Baker Cancer Center - Calgary	Calgary	Alberta	Canada	T2N 4N2
148	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
149	Credit Valley Hospital	Mississauga	Ontario	Canada	L5M 2N1
150	Ottawa Regional Cancer Centre	Ottawa	Ontario	Canada	K1H 1C4
151	St. Michael's Hospital - Toronto	Toronto	Ontario	Canada	M5B 1W8
152	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2L-4M1
153	Royal Victoria Hospital - Montreal	Montreal	Quebec	Canada	H3A 1A1
154	Montreal General Hospital	Montreal	Quebec	Canada	H3G 1A4
155	Jewish General Hospital - Montreal	Montreal	Quebec	Canada	H3T 1E2
156	St. Mary's Hospital Center	Montreal	Quebec	Canada	H3T 1M5
157	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

None provided.

• Responsible Party: NSABP Foundation Inc
• ClinicalTrials.gov Identifier: NCT00003782
• Other Study ID Numbers: NSABP B-30; CDR0000066914
• First Posted: Jan 27, 2003
• Last Update Posted: Jan 18, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by NSABP Foundation Inc: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Cyclophosphamide; Docetaxel; Doxorubicin

Study Results

Participant Flow

Arm/Group Title	Arm 1: Doxorubicin + Cyclophosphamide, Then Docetaxel	Arm 2: Doxorubicin + Docetaxel	Arm 3: Doxorubicin + Docetaxel + Cyclophosphamide
Arm/Group Description	Doxorubicin + Cyclophosphamide, then Docetaxel	Doxorubicin + Docetaxel	Doxorubicin + Docetaxel + Cyclophosphamide
Period Title: Overall Study
STARTED	1783	1784	1784
COMPLETED	1753	1753	1758
NOT COMPLETED	30	31	26

Baseline Characteristics

Arm/Group Title	Doxorubicin + Cyclophosphamide, Then Docetaxel	Doxorubicin + Docetaxel	Doxorubicin + Docetaxel + Cyclophosphamide	Total
Arm/Group Description	Doxorubicin + Cyclophosphamide, then Docetaxel	Doxorubicin + Docetaxel	Doxorubicin + Docetaxel + Cyclophosphamide	Total of all reporting groups
Overall Participants	1783	1784	1784	5351
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (9.8)	50 (9.5)	51 (9.9)	51 (9.7)
Sex: Female, Male (Count of Participants)
Female	1783 100%	1784 100%	1784 100%	5351 100%
Male	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Time Frame	8 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Doxorubicin + Cyclophosphamide, Then Docetaxel	Arm 2: Doxorubicin + Docetaxel	Arm 3: Doxorubicin + Docetaxel + Cyclophosphamide
Arm/Group Description	Doxorubicin + Cyclophosphamide, then Docetaxel	Doxorubicin + Docetaxel	Doxorubicin + Docetaxel + Cyclophosphamide
Measure Participants	1753	1753	1758
Number [percentage of patients alive]	83	79	79

2. Primary Outcome

Title	Disease Free Survival
Time Frame	time to event: breast cancer recurrence; second primary cancer; death from any cause as a first event

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Toxicities Among the 3 Regimens
Time Frame	9 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Quality of Life Among Breast Cancer Patients
Time Frame	baseline, 9 weeks, and 6, 12, 18, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Amenorrhea in Premenopausal Women
Time Frame	baseline, 9 weeks, and 6, 12, 18, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Participants at Risk includes any patient who submitted an AE form.
Arm/Group Title	Doxorubicin + Cyclophosphamide, Then Docetaxel		Doxorubicin + Docetaxel		Doxorubicin + Docetaxel + Cyclophosphamide
Arm/Group Description	Doxorubicin + Cyclophosphamide, then Docetaxel		Doxorubicin + Docetaxel		Doxorubicin + Docetaxel + Cyclophosphamide
All Cause Mortality
	Doxorubicin + Cyclophosphamide, Then Docetaxel		Doxorubicin + Docetaxel		Doxorubicin + Docetaxel + Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Doxorubicin + Cyclophosphamide, Then Docetaxel		Doxorubicin + Docetaxel		Doxorubicin + Docetaxel + Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/1748 (3.8%)		43/1748 (2.5%)		46/1745 (2.6%)
Blood and lymphatic system disorders
Febrile neutropenia	2/1748 (0.1%)		1/1748 (0.1%)		7/1745 (0.4%)
Cardiac disorders
Cardiac disorders - Other, specify	3/1748 (0.2%)		1/1748 (0.1%)		1/1745 (0.1%)
Conduction disorder	0/1748 (0%)		0/1748 (0%)		1/1745 (0.1%)
Myocardial infarction	0/1748 (0%)		1/1748 (0.1%)		0/1745 (0%)
Ventricular arrhythmia	1/1748 (0.1%)		0/1748 (0%)		1/1745 (0.1%)
Left ventricular systolic dysfunction	0/1748 (0%)		1/1748 (0.1%)		1/1745 (0.1%)
Gastrointestinal disorders
Colitis	1/1748 (0.1%)		1/1748 (0.1%)		2/1745 (0.1%)
Diarrhea	0/1748 (0%)		1/1748 (0.1%)		1/1745 (0.1%)
Duodenal ulcer	0/1748 (0%)		1/1748 (0.1%)		0/1745 (0%)
Esophagitis	0/1748 (0%)		1/1748 (0.1%)		0/1745 (0%)
Gastrointestinal disorders - Other, specify	1/1748 (0.1%)		0/1748 (0%)		1/1745 (0.1%)
Mucositis oral	0/1748 (0%)		1/1748 (0.1%)		0/1745 (0%)
Typhlitis	1/1748 (0.1%)		3/1748 (0.2%)		1/1745 (0.1%)
Vomiting	2/1748 (0.1%)		1/1748 (0.1%)		0/1745 (0%)
General disorders
General disorders and administration site conditions - Other, specify	0/1748 (0%)		0/1748 (0%)		1/1745 (0.1%)
Hepatobiliary disorders
Hepatic failure	0/1748 (0%)		1/1748 (0.1%)		0/1745 (0%)
Hepatobiliary disorders - Other, specify	0/1748 (0%)		0/1748 (0%)		1/1745 (0.1%)
Immune system disorders
Anaphylaxis	1/1748 (0.1%)		3/1748 (0.2%)		0/1745 (0%)
Infections and infestations
Infections and infestations - Other, specify	9/1748 (0.5%)		7/1748 (0.4%)		10/1745 (0.6%)
Wound infection	1/1748 (0.1%)		1/1748 (0.1%)		0/1745 (0%)
Injury, poisoning and procedural complications
Dermatitis radiation	0/1748 (0%)		0/1748 (0%)		2/1745 (0.1%)
Investigations
Alanine aminotransferase increased (ALT/SGPT)	1/1748 (0.1%)		0/1748 (0%)		1/1745 (0.1%)
Aspartate aminotransferase increased (AST/SGOT)	1/1748 (0.1%)		1/1748 (0.1%)		2/1745 (0.1%)
Blood bilirubin increased	0/1748 (0%)		0/1748 (0%)		1/1745 (0.1%)
Creatinine increased	1/1748 (0.1%)		1/1748 (0.1%)		0/1745 (0%)
Neutrophil count decreased	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
White blood cell decreased	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Metabolism and nutrition disorders
Anorexia	0/1748 (0%)		2/1748 (0.1%)		1/1745 (0.1%)
Dehydration	2/1748 (0.1%)		0/1748 (0%)		2/1745 (0.1%)
Hyperglycemia	14/1748 (0.8%)		5/1748 (0.3%)		2/1745 (0.1%)
Hypertriglyceridemia	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Hypocalcemia	0/1748 (0%)		1/1748 (0.1%)		0/1745 (0%)
Hypokalemia	1/1748 (0.1%)		0/1748 (0%)		1/1745 (0.1%)
Hyponatremia	0/1748 (0%)		1/1748 (0.1%)		1/1745 (0.1%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Nervous system disorders
Intracranial hemorrhage	0/1748 (0%)		1/1748 (0.1%)		0/1745 (0%)
Nervous system disorders - Other, specify	2/1748 (0.1%)		4/1748 (0.2%)		2/1745 (0.1%)
Peripheral motor neuropathy	2/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Vasovagal reaction	0/1748 (0%)		0/1748 (0%)		1/1745 (0.1%)
Psychiatric disorders
Anxiety	1/1748 (0.1%)		0/1748 (0%)		1/1745 (0.1%)
Confusion	2/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Depression	5/1748 (0.3%)		6/1748 (0.3%)		2/1745 (0.1%)
Psychosis	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Renal and urinary disorders
Hematuria	0/1748 (0%)		0/1748 (0%)		1/1745 (0.1%)
Urinary tract obstruction	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	2/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Dyspnea	6/1748 (0.3%)		0/1748 (0%)		3/1745 (0.2%)
Hypoxia	1/1748 (0.1%)		1/1748 (0.1%)		0/1745 (0%)
Pneumonitis	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Vascular disorders
Capillary leak syndrome	0/1748 (0%)		0/1748 (0%)		1/1745 (0.1%)
Hypertension	1/1748 (0.1%)		0/1748 (0%)		0/1745 (0%)
Hypotension	1/1748 (0.1%)		1/1748 (0.1%)		0/1745 (0%)
Thromboembolic event	12/1748 (0.7%)		4/1748 (0.2%)		8/1745 (0.5%)
Visceral arterial ischemia	0/1748 (0%)		0/1748 (0%)		2/1745 (0.1%)
Other (Not Including Serious) Adverse Events
	Doxorubicin + Cyclophosphamide, Then Docetaxel		Doxorubicin + Docetaxel		Doxorubicin + Docetaxel + Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	845/1748 (48.3%)		561/1748 (32.1%)		641/1745 (36.7%)
Blood and lymphatic system disorders
Febrile neutropenia	383/1748 (21.9%)		223/1748 (12.8%)		275/1745 (15.8%)
Gastrointestinal disorders
Diarrhea	78/1748 (4.5%)		66/1748 (3.8%)		111/1745 (6.4%)
Nausea	162/1748 (9.3%)		127/1748 (7.3%)		155/1745 (8.9%)
Vomiting	140/1748 (8%)		90/1748 (5.1%)		119/1745 (6.8%)
General disorders
Fatigue	212/1748 (12.1%)		135/1748 (7.7%)		167/1745 (9.6%)
Infections and infestations
Infections and infestations - Other, specify	200/1748 (11.4%)		144/1748 (8.2%)		137/1745 (7.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	126/1748 (7.2%)		22/1748 (1.3%)		33/1745 (1.9%)
Myalgia	148/1748 (8.5%)		29/1748 (1.7%)		35/1745 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.