Chemotherapy in Treating Women With Breast Cancer That Can Be Surgically Removed
Overview[ - collapse ][ - ]
| Purpose | 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 | Breast Cancer |
| Intervention | Drug: Cyclophosphamide Drug: Docetaxel Drug: Doxorubicin Drug: Tamoxifen |
| Phase | Phase 3 |
| Sponsor | National Surgical Adjuvant Breast and Bowel Project (NSABP) |
| Responsible Party | National Surgical Adjuvant Breast and Bowel Project (NSABP) |
| ClinicalTrials.gov Identifier | NCT00002707 |
| First Received | November 1, 1999 |
| Last Updated | February 2, 2010 |
| Last verified | February 2010 |
Tracking Information[ + expand ][ + ]
| First Received Date | November 1, 1999 |
|---|---|
| Last Updated Date | February 2, 2010 |
| Start Date | December 1995 |
| Estimated Primary Completion Date | February 2010 |
| Current Primary Outcome Measures | 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 Frame: Time from randomization to death from any cause.] [Designated as safety issue: No] |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Chemotherapy in Treating Women With Breast Cancer That Can Be Surgically Removed |
|---|---|
| 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 |
| 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. |
| 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 Type | Interventional |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Breast Cancer |
| Intervention | 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 |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 2411 |
| Estimated Completion Date | February 2010 |
| Estimated Primary Completion Date | June 2002 |
| Eligibility Criteria | 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) |
| Gender | Female |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Canada |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00002707 |
|---|---|
| Other Study ID Numbers | NSABP B-27 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | National Surgical Adjuvant Breast and Bowel Project (NSABP) |
| Study Sponsor | National Surgical Adjuvant Breast and Bowel Project (NSABP) |
| Collaborators | National Cancer Institute (NCI) |
| Investigators | Study Chair: Harry D. Bear, MD, PhD Massey Cancer Center |
| Verification Date | February 2010 |
Locations[ + expand ][ + ]
| Huntsville Hospital System | Huntsville, Alabama, United States, 35801 |
|---|---|
| CCOP - Greater Phoenix | Phoenix, Arizona, United States, 85006-2726 |
| Sutter Health Western Division Cancer Research Group | Greenbrae, California, United States, 94904 |
| Loma Linda University Medical Center | Loma Linda, California, United States, 92354 |
| Saint Mary Medical Center - Long Beach | Long Beach, California, United States, 90813-0887 |
| Beckman Research Institute, City of Hope | Los Angeles, California, United States, 91010 |
| CCOP - Bay Area Tumor Institute | Oakland, California, United States, 94609-3305 |
| Chao Family Comprehensive Cancer Center | Orange, California, United States, 92868 |
| Comprehensive Cancer Centers of the Desert | Palm Springs, California, United States, 92262 |
| Kaiser Permanente-Southern California Permanente Medical Group | San Diego, California, United States, 92120 |
| Catholic Healthcare West - Westbay Region | San Francisco, California, United States, 94107-1728 |
| CCOP - Santa Rosa Memorial Hospital | Santa Rosa, California, United States, 95403 |
| Kaiser Permanente Medical Center - Vallejo | Vallejo, California, United States, 94589 |
| CCOP - Colorado Cancer Research Program, Inc. | Denver, Colorado, United States, 80209-5031 |
| University of Colorado Cancer Center | Denver, Colorado, United States, 80262 |
| University of Connecticut Health Center | Farmington, Connecticut, United States, 06360-7106 |
| Hartford Hospital | Hartford, Connecticut, United States, 06102-5037 |
| CCOP - Christiana Care Health Services | Wilmington, Delaware, United States, 19899 |
| George Washington University Cancer Center | Washington, District of Columbia, United States, 20037 |
| Halifax Medical Center | Daytona Beach, Florida, United States, 32114 |
| Baptist Regional Cancer Institute - Jacksonville | Jacksonville, Florida, United States, 32207 |
| Sylvester Cancer Center, University of Miami | Miami, Florida, United States, 33136 |
| CCOP - Mount Sinai Medical Center | Miami Beach, Florida, United States, 33140 |
| Good Samaritan Medical Center | West Palm Beach, Florida, United States, 33401 |
| Winship Cancer Institute | Atlanta, Georgia, United States, 30322 |
| CCOP - Atlanta Regional | Atlanta, Georgia, United States, 30342-1701 |
| Medical College of Georgia Comprehensive Cancer Center | Augusta, Georgia, United States, 30912-4000 |
| Dwight David Eisenhower Army Medical Center | Fort Gordon, Georgia, United States, 30905-5650 |
| Cancer Research Center of Hawaii | Honolulu, Hawaii, United States, 96813 |
| North Idaho Cancer Center | Coeur d'Alene, Idaho, United States, 83814 |
| Illinois Masonic Medical Center | Chicago, Illinois, United States, 60657 |
| CCOP - Evanston | Evanston, Illinois, United States, 60201 |
| CCOP - Illinois Oncology Research Association | Peoria, Illinois, United States, 61602 |
| Rockford Clinic | Rockford, Illinois, United States, 61103 |
| CCOP - Carle Cancer Center | Urbana, Illinois, United States, 61801 |
| St. Vincent Hospital and Health Care Center | Indianapolis, Indiana, United States, 46260 |
| Memorial Hospital of South Bend | South Bend, Indiana, United States, 46601 |
| CCOP - Iowa Oncology Research Association | Des Moines, Iowa, United States, 50309-1016 |
| University of Iowa Hospitals and Clinics | Iowa City, Iowa, United States, 52242 |
| CCOP - Wichita | Wichita, Kansas, United States, 67214-3882 |
| Lucille Parker Markey Cancer Center, University of Kentucky | Lexington, Kentucky, United States, 40536-0093 |
| Norton Healthcare System | Louisville, Kentucky, United States, 40202-5070 |
| CCOP - Ochsner | New Orleans, Louisiana, United States, 70121 |
| Louisiana State University Medical Center - New Orleans | New Orleans, Louisiana, United States, 70112 |
| Tulane University School of Medicine | New Orleans, Louisiana, United States, 70112 |
| Eastern Maine Medical Center | Bangor, Maine, United States, 04401 |
| Franklin Square Hospital Center | Baltimore, Maryland, United States, 21237 |
| National Naval Medical Center | Bethesda, Maryland, United States, 20889-5000 |
| Regional Cancer Therapy Center - Frederick | Frederick, Maryland, United States, 21701 |
| Boston Medical Center | Boston, Massachusetts, United States, 02118 |
| Lahey Clinic - Burlington | Burlington, Massachusetts, United States, 01805 |
| Berkshire Medical Center | Pittsfield, Massachusetts, United States, 01201 |
| Baystate Medical Center | Springfield, Massachusetts, United States, 01199 |
| CCOP - Ann Arbor Regional | Ann Arbor, Michigan, United States, 48106 |
| Henry Ford Hospital | Detroit, Michigan, United States, 48202 |
| Michigan State University | East Lansing, Michigan, United States, 48824 |
| CCOP - Grand Rapids Clinical Oncology Program | Grand Rapids, Michigan, United States, 49503 |
| CCOP - Kalamazoo | Kalamazoo, Michigan, United States, 49007-3731 |
| Providence Hospital - Southfield | Southfield, Michigan, United States, 48075-9975 |
| CCOP - Duluth | Duluth, Minnesota, United States, 55805 |
| Hennepin County Medical Center - Minneapolis | Minneapolis, Minnesota, United States, 55415 |
| University of Mississippi Medical Center | Jackson, Mississippi, United States, 39216-4505 |
| Ellis Fischel Cancer Center - Columbia | Columbia, Missouri, United States, 65203 |
| CCOP - St. Louis-Cape Girardeau | Saint Louis, Missouri, United States, 63141 |
| St. Louis University School of Medicine | Saint Louis, Missouri, United States, 63104 |
| CCOP - Cancer Research for the Ozarks | Springfield, Missouri, United States, 65807 |
| CCOP - Montana Cancer Consortium | Billings, Montana, United States, 59101 |
| CCOP - Missouri Valley Cancer Consortium | Omaha, Nebraska, United States, 68131 |
| Methodist Cancer Center - Omaha | Omaha, Nebraska, United States, 68114 |
| CCOP - Southern Nevada Cancer Research Foundation | Las Vegas, Nevada, United States, 89106 |
| Cooper Cancer Institute | Camden, New Jersey, United States, 08103 |
| Trinitas Hospital - Jersey Street Campus | Elizabeth, New Jersey, United States, 07201 |
| CCOP - Northern New Jersey | Hackensack, New Jersey, United States, 07601 |
| Hackensack University Medical Center | Hackensack, New Jersey, United States, 07601 |
| Cancer Institute of New Jersey at Hamilton | Hamilton, New Jersey, United States, 08690 |
| Cancer Institute of New Jersey | New Brunswick, New Jersey, United States, 08901 |
| Newark Beth Israel Medical Center | Newark, New Jersey, United States, 07112 |
| University of Medicine and Dentistry of New Jersey | Newark, New Jersey, United States, 07103-2425 |
| Overlook Hospital | Summit, New Jersey, United States, 07902-0220 |
| University of New Mexico Cancer Research & Treatment Center | Albuquerque, New Mexico, United States, 87131 |
| CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. | Syracuse, New York, United States, 13210 |
| Lineberger Comprehensive Cancer Center, UNC | Chapel Hill, North Carolina, United States, 27599-7295 |
| East Carolina University School of Medicine | Greenville, North Carolina, United States, 27858-4354 |
| Comprehensive Cancer Center of Wake Forest University Baptist Medical Center | Winston-Salem, North Carolina, United States, 27157-1082 |
| CCOP - Southeast Cancer Control Consortium | Winston-Salem, North Carolina, United States, 27104-4241 |
| CCOP - Merit Care Hospital | Fargo, North Dakota, United States, 58122 |
| Akron City Hospital | Akron, Ohio, United States, 44309 |
| Aultman Cancer Center | Canton, Ohio, United States, 44710 |
| Jewish Hospital of Cincinnati, Inc. | Cincinnati, Ohio, United States, 45236 |
| Barrett Cancer Center, The University Hospital | Cincinnati, Ohio, United States, 45219 |
| South Pointe Hospital | Cleveland, Ohio, United States, 44122 |
| CCOP - Columbus | Columbus, Ohio, United States, 43206 |
| Arthur G. James Cancer Hospital - Ohio State University | Columbus, Ohio, United States, 43210 |
| CCOP - Dayton | Kettering, Ohio, United States, 45429 |
| CCOP - Sooner State | Tulsa, Oklahoma, United States, 74136 |
| CCOP - Columbia River Program | Portland, Oregon, United States, 97213 |
| Oregon Cancer Center at Oregon Health Sciences University | Portland, Oregon, United States, 97201-3098 |
| Lehigh Valley Hospital | Allentown, Pennsylvania, United States, 18105-1556 |
| St. Luke's Network - Bethlehem | Bethlehem, Pennsylvania, United States, 18015 |
| Geisinger Medical Center | Danville, Pennsylvania, United States, 17822-2001 |
| Allegheny General Hospital | Pittsburgh, Pennsylvania, United States, 15212-4772 |
| University of Pittsburgh Cancer Institute | Pittsburgh, Pennsylvania, United States, 15213 |
| Mercy Hospital Cancer Center - Scranton | Scranton, Pennsylvania, United States, 18501 |
| CCOP - MainLine Health | Wynnewood, Pennsylvania, United States, 19096 |
| York Hospital | York, Pennsylvania, United States, 17315 |
| Kent County Memorial Hospital - Rhode Island | Warwick, Rhode Island, United States, 02886 |
| Medical University of South Carolina | Charleston, South Carolina, United States, 29425-0721 |
| CCOP - Greenville | Greenville, South Carolina, United States, 29615 |
| CCOP - Upstate Carolina | Spartanburg, South Carolina, United States, 29303 |
| CCOP - Sioux Community Cancer Consortium | Sioux Falls, South Dakota, United States, 57105-1080 |
| CCOP - Baptist Cancer Institute | Memphis, Tennessee, United States, 38117 |
| Medical Group of Texas | Dallas, Texas, United States, 75243 |
| Simmons Cancer Center - Dallas | Dallas, Texas, United States, 75235-9154 |
| University of Texas Medical Branch | Galveston, Texas, United States, 77555-1329 |
| Baylor College of Medicine | Houston, Texas, United States, 77030 |
| Joe Arrington Cancer Research and Treatment Center | Lubbock, Texas, United States, 79410-1894 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas, United States, 78284-7811 |
| CCOP - Scott and White Hospital | Temple, Texas, United States, 76508 |
| Utah Valley Regional Medical Center - Provo | Provo, Utah, United States, 84604 |
| CCOP - Southwestern Vermont Regional Cancer Center | Bennington, Vermont, United States, 05201 |
| Vermont Cancer Center | Burlington, Vermont, United States, 05401-3498 |
| Virginia Oncology Associates | Newport News, Virginia, United States, 23606 |
| Eastern Virginia Medical School | Norfolk, Virginia, United States, 23507 |
| MBCCOP - Massey Cancer Center | Richmond, Virginia, United States, 23298-0037 |
| CCOP - Virginia Mason Research Center | Seattle, Washington, United States, 98101 |
| Puget Sound Oncology Consortium | Seattle, Washington, United States, 98109 |
| CCOP - Northwest | Tacoma, Washington, United States, 98405-0986 |
| David Lee Cancer Center | Charleston, West Virginia, United States, 25304 |
| West Virginia University Hospitals | Morgantown, West Virginia, United States, 26506-9162 |
| Camden-Clark Memorial Hospital | Parkersburg, West Virginia, United States, 26102 |
| St. Vincent Hospital | Green Bay, Wisconsin, United States, 54307-3508 |
| CCOP - Marshfield Medical Research and Education Foundation | Marshfield, Wisconsin, United States, 54449 |
| Medical College of Wisconsin | Milwaukee, Wisconsin, United States, 53226 |
| St. Luke's Medical Center | Milwaukee, Wisconsin, United States, 53215 |
| Tom Baker Cancer Center - Calgary | Calgary, Alberta, Canada, T2N 4N2 |
| Cross Cancer Institute | Edmonton, Alberta, Canada, T6G 1Z2 |
| CancerCare Manitoba | Winnipeg, Manitoba, Canada, R3E 0V9 |
| Credit Valley Hospital | Mississauga, Ontario, Canada, L5M 2N1 |
| Centre Hospitalier de l'Universite de Montreal | Montreal, Quebec, Canada, H2L-4M1 |
| St. Mary's Hospital Center | Montreal, Quebec, Canada, H3T 1M5 |
| Jewish General Hospital - Montreal | Montreal, Quebec, Canada, H3T 1E2 |
| Royal Victoria Hospital - Montreal | Montreal, Quebec, Canada, H3A 1A1 |
| Montreal General Hospital | Montreal, Quebec, Canada, H3G 1A4 |
| Hopital du Saint-Sacrament, Quebec | Quebec City, Quebec, Canada, G1S 4L8 |
| L'Hopital Laval | Ste-Foy, Quebec, Canada, G1V 4G5 |