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Chemotherapy in Treating Women With Breast Cancer That Can Be Surgically Removed

Sponsor
NSABP Foundation Inc (Other)
Overall Status
Completed
CT.gov ID
NCT00002707
Collaborator
National Cancer Institute (NCI) (NIH)
2,411
Enrollment
145
Locations
3
Arms
170.1
Duration (Months)
16.6
Patients Per Site
0.1
Patients Per Site Per Month

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. It is not yet known if chemotherapy given before surgery is more effective with or without docetaxel given before or after surgery for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy using doxorubicin and cyclophosphamide with or without docetaxel in treating women who have stage II or stage III breast cancer.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

OBJECTIVES: I. Compare overall and disease-free survival in patients with operable adenocarcinoma of the breast treated with 4 courses of preoperative doxorubicin and cyclophosphamide (AC) alone vs 4 courses of preoperative or postoperative docetaxel (TXT) following 4 courses of preoperative AC. II. Evaluate whether the addition of preoperative TXT to preoperative AC results in improved rates of clinical and pathologic locoregional tumor response. III. Assess whether the addition of preoperative TXT to preoperative AC results in improved rates of breast conservation. IV. Assess whether postoperative TXT improves disease-free and overall survival in patients who receive preoperative AC, especially in certain subgroups of patients (e.g., those with pathologically positive nodes).

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 50 vs 50 and over), clinical tumor size (less than 2.1 cm vs 2.1-4.0 cm vs greater than 4.0 cm), clinical nodal status (negative vs positive), and participating center. Patients are randomized to one of three treatment arms. Arm I: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1 every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After completion of chemotherapy, patients are offered surgery (e.g., lumpectomy with axillary node dissection, or modified radical mastectomy). Post-operative radiotherapy is given post-lumpectomy. Arm II: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours followed by docetaxel IV over 1 hour on day 1 once every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After the completion of chemotherapy, surgery is offered (as in arm I). Radiotherapy follows surgery in post-lumpectomy patients. Arm III: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1 every 21 days for 4 courses. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After completion of chemotherapy, surgery is offered (as in arm I). After surgical recovery, docetaxel IV is given over 1 hour once every 21 days for 4 courses. Radiotherapy follows docetaxel in post-lumpectomy patients. Chemotherapy is repeated every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 2,400 patients will be accrued for this study within 5 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
2411 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A RANDOMIZED TRIAL COMPARING PREOPERATIVE DOXORUBICIN (ADRIAMYCIN)/CYCLOPHOSPHAMIDE (AC) TO PREOPERATIVE AC FOLLOWED BY PREOPERATIVE DOCETAXEL (TAXOTERE) AND TO PREOPERATIVE AC FOLLOWED BY POSTOPERATIVE DOCETAXEL IN PATIENTS WITH OPERABLE CARCINOMA OF THE BREAST
Study Start Date :
Dec 1, 1995
Actual Primary Completion Date :
Jun 1, 2002
Actual Study Completion Date :
Feb 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group 2

doxorubicin and cyclophosphamide plus Taxotere prior to surgery plus tamoxifen

Drug: Cyclophosphamide
600 mg/m2 IV every 21 days for 4 cycles

Drug: Docetaxel
100 mg/m2 IV every 21 days for 4 cycles

Drug: Doxorubicin
60 mg/m2 IV every 21 days fo 4 cycles

Drug: Tamoxifen
20 mg p.o. once daily for 5 years starting on day 1 of ther first AC cycle
Experimental: Group 3

doxorubicin and cyclophosphamide followed by surgery followed by taxotere plus tamoxifen

Drug: Cyclophosphamide
600 mg/m2 IV every 21 days for 4 cycles

Drug: Docetaxel
100 mg/m2 IV every 21 days for 4 cycles

Drug: Doxorubicin
60 mg/m2 IV every 21 days fo 4 cycles

Drug: Tamoxifen
20 mg p.o. once daily for 5 years starting on day 1 of ther first AC cycle
Active Comparator: Group 1

doxorubicin and cyclophosphamide plus tamoxifen

Drug: Cyclophosphamide
600 mg/m2 IV every 21 days for 4 cycles

Drug: Doxorubicin
60 mg/m2 IV every 21 days fo 4 cycles

Drug: Tamoxifen
20 mg p.o. once daily for 5 years starting on day 1 of ther first AC cycle

Outcome Measures

Primary Outcome Measures

  1. Determine if 4 cycle of pre-op or post-op Taxotere given after 4 cycles of pre-op AC will more effectively prolong survival (S) than does 4 cycles of pre-op AC alone. [Time from randomization to death from any cause.]

Secondary Outcome Measures

  1. Prolonging disease-free survival (DFS). [Time from randomization to first related event of inoperable disease; residual disease following surgery; local, regional or distant recurrence; second primary cancer; death from any cause other than cancer.]

  2. Clinical loco-regional tumor response to preoperative chemotherapy. [3-4 weeks after the last cycle of pre-op chemotherapy.]

  3. Pathologic loco-regional tumor response to pre-op chemotherapy. [At time of surgery.]

  4. Breast conservation assessment. [Assessed following surgery.]

  5. Evaluate if post-op Taxotere is of benefit in patients who received pre-op AC and, if so, whether it is of benefit in certain subgroups of patients. [DFS and S will be assessed in patient subgroups.]

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No

DISEASE CHARACTERISTICS: Histologically or cytologically proven invasive adenocarcinoma of the breast Fine-needle aspiration is acceptable Core or Tru-cut biopsies are preferable No more than 63 days between initial diagnosis and randomization Tumor palpable on clinical exam and confined to the breast and ipsilateral axilla If clinically negative axillary nodes (N0): primary tumor greater than 1 cm (T1c-T3) If clinically positive axillary nodes (N1): any size primary tumor (T1-3) No N2 disease, i.e., ipsilateral nodes clinically fixed to one another or to other structures No skeletal pain unless: Bone scan and/or roentgenologic exam negative for metastatic disease Suspicious findings confirmed as benign by x-ray, MRI, or biopsy No ulceration, erythema, skin infiltration (complete fixation), or peau d'orange, or skin edema of any magnitude Tethering or dimpling of skin or nipple inversion allowed No bilateral malignancy Suspicious contralateral mass proven benign on biopsy allowed None of the following unless proven benign on biopsy: Suspicious palpable nodes in contralateral axilla Palpable supraclavicular or infraclavicular nodes Hormone receptor status: Any status

PATIENT CHARACTERISTICS: Age: Any age Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: At least 10 years (exclusive of cancer diagnosis) Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal AST/ALT normal Alkaline phosphatase normal Renal: Creatinine normal Cardiovascular: No active cardiac disease that would preclude doxorubicin, e.g.: Documented myocardial infarction History of congestive heart failure Angina pectoris requiring medication Valvular disease with documented cardiac function compromise Arrhythmia associated with heart failure or cardiac dysfunction Poorly controlled hypertension, i.e., diastolic blood pressure greater than 100 mm Hg Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG unless left ventricular ejection fraction at least 45% by MUGA Other: No other malignancy within the past 10 years except: Segmentally resected lobular carcinoma in situ of the ipsilateral or contralateral breast Effectively treated nonmelanomatous skin cancer Surgically treated carcinoma in situ of the cervix No systemic disease that would preclude therapy No psychiatric or addictive disorder that would preclude informed consent Geographically accessible for follow-up Not pregnant

PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer No prior anthracyclines for any malignancy No concurrent sex hormones (e.g., birth control pills or ovarian replacement therapy)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Huntsville Hospital System Huntsville Alabama United States 35801
2 CCOP - Greater Phoenix Phoenix Arizona United States 85006-2726
3 Sutter Health Western Division Cancer Research Group Greenbrae California United States 94904
4 Loma Linda University Medical Center Loma Linda California United States 92354
5 Saint Mary Medical Center - Long Beach Long Beach California United States 90813-0887
6 Beckman Research Institute, City of Hope Los Angeles California United States 91010
7 CCOP - Bay Area Tumor Institute Oakland California United States 94609-3305
8 Chao Family Comprehensive Cancer Center Orange California United States 92868
9 Comprehensive Cancer Centers of the Desert Palm Springs California United States 92262
10 Kaiser Permanente-Southern California Permanente Medical Group San Diego California United States 92120
11 Catholic Healthcare West - Westbay Region San Francisco California United States 94107-1728
12 CCOP - Santa Rosa Memorial Hospital Santa Rosa California United States 95403
13 Kaiser Permanente Medical Center - Vallejo Vallejo California United States 94589
14 CCOP - Colorado Cancer Research Program, Inc. Denver Colorado United States 80209-5031
15 University of Colorado Cancer Center Denver Colorado United States 80262
16 University of Connecticut Health Center Farmington Connecticut United States 06360-7106
17 Hartford Hospital Hartford Connecticut United States 06102-5037
18 CCOP - Christiana Care Health Services Wilmington Delaware United States 19899
19 George Washington University Cancer Center Washington District of Columbia United States 20037
20 Halifax Medical Center Daytona Beach Florida United States 32114
21 Baptist Regional Cancer Institute - Jacksonville Jacksonville Florida United States 32207
22 CCOP - Mount Sinai Medical Center Miami Beach Florida United States 33140
23 Sylvester Cancer Center, University of Miami Miami Florida United States 33136
24 Good Samaritan Medical Center West Palm Beach Florida United States 33401
25 Winship Cancer Institute Atlanta Georgia United States 30322
26 CCOP - Atlanta Regional Atlanta Georgia United States 30342-1701
27 Medical College of Georgia Comprehensive Cancer Center Augusta Georgia United States 30912-4000
28 Dwight David Eisenhower Army Medical Center Fort Gordon Georgia United States 30905-5650
29 Cancer Research Center of Hawaii Honolulu Hawaii United States 96813
30 North Idaho Cancer Center Coeur d'Alene Idaho United States 83814
31 Illinois Masonic Medical Center Chicago Illinois United States 60657
32 CCOP - Evanston Evanston Illinois United States 60201
33 CCOP - Illinois Oncology Research Association Peoria Illinois United States 61602
34 Rockford Clinic Rockford Illinois United States 61103
35 CCOP - Carle Cancer Center Urbana Illinois United States 61801
36 St. Vincent Hospital and Health Care Center Indianapolis Indiana United States 46260
37 Memorial Hospital of South Bend South Bend Indiana United States 46601
38 CCOP - Iowa Oncology Research Association Des Moines Iowa United States 50309-1016
39 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
40 CCOP - Wichita Wichita Kansas United States 67214-3882
41 Lucille Parker Markey Cancer Center, University of Kentucky Lexington Kentucky United States 40536-0093
42 Norton Healthcare System Louisville Kentucky United States 40202-5070
43 Louisiana State University Medical Center - New Orleans New Orleans Louisiana United States 70112
44 Tulane University School of Medicine New Orleans Louisiana United States 70112
45 CCOP - Ochsner New Orleans Louisiana United States 70121
46 Eastern Maine Medical Center Bangor Maine United States 04401
47 Franklin Square Hospital Center Baltimore Maryland United States 21237
48 National Naval Medical Center Bethesda Maryland United States 20889-5000
49 Regional Cancer Therapy Center - Frederick Frederick Maryland United States 21701
50 Boston Medical Center Boston Massachusetts United States 02118
51 Lahey Clinic - Burlington Burlington Massachusetts United States 01805
52 Berkshire Medical Center Pittsfield Massachusetts United States 01201
53 Baystate Medical Center Springfield Massachusetts United States 01199
54 CCOP - Ann Arbor Regional Ann Arbor Michigan United States 48106
55 Henry Ford Hospital Detroit Michigan United States 48202
56 Michigan State University East Lansing Michigan United States 48824
57 CCOP - Grand Rapids Clinical Oncology Program Grand Rapids Michigan United States 49503
58 CCOP - Kalamazoo Kalamazoo Michigan United States 49007-3731
59 Providence Hospital - Southfield Southfield Michigan United States 48075-9975
60 CCOP - Duluth Duluth Minnesota United States 55805
61 Hennepin County Medical Center - Minneapolis Minneapolis Minnesota United States 55415
62 University of Mississippi Medical Center Jackson Mississippi United States 39216-4505
63 Ellis Fischel Cancer Center - Columbia Columbia Missouri United States 65203
64 St. Louis University School of Medicine Saint Louis Missouri United States 63104
65 CCOP - St. Louis-Cape Girardeau Saint Louis Missouri United States 63141
66 CCOP - Cancer Research for the Ozarks Springfield Missouri United States 65807
67 CCOP - Montana Cancer Consortium Billings Montana United States 59101
68 Methodist Cancer Center - Omaha Omaha Nebraska United States 68114
69 CCOP - Missouri Valley Cancer Consortium Omaha Nebraska United States 68131
70 CCOP - Southern Nevada Cancer Research Foundation Las Vegas Nevada United States 89106
71 Cooper Cancer Institute Camden New Jersey United States 08103
72 Trinitas Hospital - Jersey Street Campus Elizabeth New Jersey United States 07201
73 CCOP - Northern New Jersey Hackensack New Jersey United States 07601
74 Hackensack University Medical Center Hackensack New Jersey United States 07601
75 Cancer Institute of New Jersey at Hamilton Hamilton New Jersey United States 08690
76 Cancer Institute of New Jersey New Brunswick New Jersey United States 08901
77 University of Medicine and Dentistry of New Jersey Newark New Jersey United States 07103-2425
78 Newark Beth Israel Medical Center Newark New Jersey United States 07112
79 Overlook Hospital Summit New Jersey United States 07902-0220
80 University of New Mexico Cancer Research & Treatment Center Albuquerque New Mexico United States 87131
81 CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. Syracuse New York United States 13210
82 Lineberger Comprehensive Cancer Center, UNC Chapel Hill North Carolina United States 27599-7295
83 East Carolina University School of Medicine Greenville North Carolina United States 27858-4354
84 CCOP - Southeast Cancer Control Consortium Winston-Salem North Carolina United States 27104-4241
85 Comprehensive Cancer Center of Wake Forest University Baptist Medical Center Winston-Salem North Carolina United States 27157-1082
86 CCOP - Merit Care Hospital Fargo North Dakota United States 58122
87 Akron City Hospital Akron Ohio United States 44309
88 Aultman Cancer Center Canton Ohio United States 44710
89 Barrett Cancer Center, The University Hospital Cincinnati Ohio United States 45219
90 Jewish Hospital of Cincinnati, Inc. Cincinnati Ohio United States 45236
91 South Pointe Hospital Cleveland Ohio United States 44122
92 CCOP - Columbus Columbus Ohio United States 43206
93 Arthur G. James Cancer Hospital - Ohio State University Columbus Ohio United States 43210
94 CCOP - Dayton Kettering Ohio United States 45429
95 CCOP - Sooner State Tulsa Oklahoma United States 74136
96 Oregon Cancer Center at Oregon Health Sciences University Portland Oregon United States 97201-3098
97 CCOP - Columbia River Program Portland Oregon United States 97213
98 Lehigh Valley Hospital Allentown Pennsylvania United States 18105-1556
99 St. Luke's Network - Bethlehem Bethlehem Pennsylvania United States 18015
100 Geisinger Medical Center Danville Pennsylvania United States 17822-2001
101 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212-4772
102 University of Pittsburgh Cancer Institute Pittsburgh Pennsylvania United States 15213
103 Mercy Hospital Cancer Center - Scranton Scranton Pennsylvania United States 18501
104 CCOP - MainLine Health Wynnewood Pennsylvania United States 19096
105 York Hospital York Pennsylvania United States 17315
106 Kent County Memorial Hospital - Rhode Island Warwick Rhode Island United States 02886
107 Medical University of South Carolina Charleston South Carolina United States 29425-0721
108 CCOP - Greenville Greenville South Carolina United States 29615
109 CCOP - Upstate Carolina Spartanburg South Carolina United States 29303
110 CCOP - Sioux Community Cancer Consortium Sioux Falls South Dakota United States 57105-1080
111 CCOP - Baptist Cancer Institute Memphis Tennessee United States 38117
112 Simmons Cancer Center - Dallas Dallas Texas United States 75235-9154
113 Medical Group of Texas Dallas Texas United States 75243
114 University of Texas Medical Branch Galveston Texas United States 77555-1329
115 Baylor College of Medicine Houston Texas United States 77030
116 Joe Arrington Cancer Research and Treatment Center Lubbock Texas United States 79410-1894
117 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78284-7811
118 CCOP - Scott and White Hospital Temple Texas United States 76508
119 Utah Valley Regional Medical Center - Provo Provo Utah United States 84604
120 CCOP - Southwestern Vermont Regional Cancer Center Bennington Vermont United States 05201
121 Vermont Cancer Center Burlington Vermont United States 05401-3498
122 Virginia Oncology Associates Newport News Virginia United States 23606
123 Eastern Virginia Medical School Norfolk Virginia United States 23507
124 MBCCOP - Massey Cancer Center Richmond Virginia United States 23298-0037
125 CCOP - Virginia Mason Research Center Seattle Washington United States 98101
126 Puget Sound Oncology Consortium Seattle Washington United States 98109
127 CCOP - Northwest Tacoma Washington United States 98405-0986
128 David Lee Cancer Center Charleston West Virginia United States 25304
129 West Virginia University Hospitals Morgantown West Virginia United States 26506-9162
130 Camden-Clark Memorial Hospital Parkersburg West Virginia United States 26102
131 St. Vincent Hospital Green Bay Wisconsin United States 54307-3508
132 CCOP - Marshfield Medical Research and Education Foundation Marshfield Wisconsin United States 54449
133 St. Luke's Medical Center Milwaukee Wisconsin United States 53215
134 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
135 Tom Baker Cancer Center - Calgary Calgary Alberta Canada T2N 4N2
136 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
137 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
138 Credit Valley Hospital Mississauga Ontario Canada L5M 2N1
139 Centre Hospitalier de l'Universite de Montreal Montreal Quebec Canada H2L-4M1
140 Royal Victoria Hospital - Montreal Montreal Quebec Canada H3A 1A1
141 Montreal General Hospital Montreal Quebec Canada H3G 1A4
142 Jewish General Hospital - Montreal Montreal Quebec Canada H3T 1E2
143 St. Mary's Hospital Center Montreal Quebec Canada H3T 1M5
144 Hopital du Saint-Sacrament, Quebec Quebec City Quebec Canada G1S 4L8
145 L'Hopital Laval Ste-Foy Quebec Canada G1V 4G5

Sponsors and Collaborators

  • NSABP Foundation Inc
  • National Cancer Institute (NCI)

Investigators

  • Study Chair: Harry D. Bear, MD, PhD, Massey Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
, ,
ClinicalTrials.gov Identifier:
NCT00002707
Other Study ID Numbers:
  • NSABP B-27
  • CDR0000064521
First Posted:
May 21, 2004
Last Update Posted:
Feb 3, 2010
Last Verified:
Feb 1, 2010
Keywords provided by , ,
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
Additional relevant MeSH terms:
Breast Neoplasms
Tamoxifen
Cyclophosphamide
Docetaxel
Doxorubicin

Study Results

No Results Posted as of Feb 3, 2010