Combination Chemotherapy in Treating Women With Stage IIIB or Stage IV Breast Cancer

A Phase II Study in Patients With Metastatic or Locally Advanced Breast Cancer to Evaluate the Worth of the Combination of Adriamycin (Doxorubicin), Taxotere (Docetaxel), and Cyclophosphamide (ATC)

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy consisting of doxorubicin, cyclophosphamide, and docetaxel in treating women with stage IIIB or stage IV breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: Taxotere; Drug: Adriamycin

Detailed Description

OBJECTIVES: I. Determine the overall response rate to doxorubicin, docetaxel, and cyclophosphamide (ATC) in women with metastatic or locally advanced breast cancer. II. Determine survival, time to first response, time to progression, and duration of response in these patients. III. Evaluate the feasibility of administering ATC for at least 4 courses. IV. Evaluate the toxicity profile of ATC and its effect on cardiac function.

OUTLINE: Patients receive intravenous doxorubicin over 15 minutes on day 0, followed by intravenous cyclophosphamide over 30 minutes. An hour after the end of the doxorubicin infusion, intravenous docetaxel is administered over 1 hour. Patients receive courses every 21 days until disease progression or unacceptable toxic effects are observed. When the maximum dose of doxorubicin is reached, treatment continues with docetaxel and cyclophosphamide. Patients with locally advanced breast cancer receive chemotherapy for at least 2 courses after documented response. Patients are followed every 6 weeks.

PROJECTED ACCRUAL: Approximately 89 patients will be accrued to this study within 14 months.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center - Calgary
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Manitoba Cancer Treatment and Research Foundation
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital - Toronto
  • Quebec
    • Montreal, Quebec, Canada, H2W-W1T8
      • Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H3G 1A4
      • Montreal General Hospital
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital - Montreal
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital - Montreal
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre Hospitalier Universitaire de Quebec, Pavillion de Quebec
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • Hôpital Laval
• Puerto Rico
  • San Juan, Puerto Rico, 00927-5800
    • MBCCOP - San Juan
  • San Juan, Puerto Rico, 00927-5800
    • Veterans Affairs Medical Center - San Juan
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Baptist Medical Center - Birmingham
    • Huntsville, Alabama, United States, 35801
      • Huntsville Hospital System
    • Mobile, Alabama, United States, 36688
      • MBCCOP - University of South Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85006-2726
      • CCOP - Greater Phoenix
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Duarte, California, United States, 91010
      • Beckman Research Institute, City of Hope
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego Cancer Center
    • La Jolla, California, United States, 92037
      • Scripps Clinic and Research Foundation - La Jolla
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Long Beach, California, United States, 90813-0887
      • Saint Mary Medical Center - Long Beach
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94627-5000
      • Naval Medical Center - Oakland
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • Sacramento, California, United States, 95820
      • Veterans Affairs Satellite Clinic - Sacramento
    • San Diego, California, United States, 92134-3202
      • Naval Medical Center - San Diego
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center - San Francisco
    • Santa Rosa, California, United States, 95403
      • CCOP - Santa Rosa Memorial Hospital
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Medical Center - Vallejo
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Cancer Center
    • Denver, Colorado, United States, 80209-5031
      • CCOP - Colorado Cancer Research Program, Inc.
  • Connecticut
    • Hartford, Connecticut, United States, 06102-5037
      • Hartford Hospital
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • CCOP - Christiana Care Health Services
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Regional Cancer Institute - Jacksonville
    • Miami, Florida, United States, 33136
      • Sylvester Cancer Center, University of Miami
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center Orlando
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Center
    • Augusta, Georgia, United States, 30912-4000
      • Medical College of Georgia Comprehensive Cancer Center
    • Decatur, Georgia, United States, 30033
      • Veterans Affairs Medical Center - Atlanta (Decatur)
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush-Presbyterian-St. Luke's Medical Center
    • Chicago, Illinois, United States, 60657
      • Illinois Masonic Medical Center
    • Evanston, Illinois, United States, 60201
      • CCOP - Evanston
    • Highland Park, Illinois, United States, 60035-2497
      • Highland Park Hospital
    • Oak Park, Illinois, United States, 60302
      • West Suburban Hospital Medical Center
    • Rockford, Illinois, United States, 61103
      • Rockford Clinic
    • Springfield, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46219
      • Community Hospitals of Indianapolis - Regional Cancer Center
    • Indianapolis, Indiana, United States, 46206-1367
      • Methodist Cancer Center - Indianapolis
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Des Moines, Iowa, United States, 10309-1016
      • CCOP - Iowa Oncology Research Association
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille Parker Markey Cancer Center, University of Kentucky
    • Louisville, Kentucky, United States, 40207
      • Baptist Hospital East - Louisville
    • Louisville, Kentucky, United States, 40202-5070
      • Norton Healthcare System
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70112
      • Veterans Affairs Medical Center - New Orleans
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Medical Center - New Orleans
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital Center
    • Bethesda, Maryland, United States, 20889-5000
      • National Naval Medical Center
    • Frederick, Maryland, United States, 21701
      • Regional Cancer Therapy Center - Frederick
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02111
      • New England Medical Center Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic - Burlington
    • Pittsfield, Massachusetts, United States, 01201
      • Berkshire Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Ann Arbor Regional
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids Clinical Oncology Program
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
    • Southfield, Michigan, United States, 48075-9975
      • Providence Hospital - Southfield
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Mississippi
    • Keesler AFB, Mississippi, United States, 39534-2576
      • Keesler Medical Center - Keesler AFB
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center - Columbia
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center - Omaha
    • Omaha, Nebraska, United States, 68131
      • CCOP - Missouri Valley Cancer Consortium
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
  • New Jersey
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Affairs Medical Center - East Orange
    • Hackensack, New Jersey, United States, 07601
      • CCOP - Northern New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Robert Wood Johnson Medical School
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Research & Treatment Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Regional Cancer Center
    • Brooklyn, New York, United States, 11203
      • State University of New York Health Science Center at Brooklyn
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center, NY
    • Rochester, New York, United States, 14607
      • Genesee Hospital - Rochester
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
    • Syracuse, New York, United States, 13210
      • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Greenville, North Carolina, United States, 27858-4354
      • East Carolina University School of Medicine
    • Winston-Salem, North Carolina, United States, 27104-4241
      • CCOP - Southeast Cancer Control Consortium
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Veterans Affairs Medical Center - Fargo
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
  • Ohio
    • Akron, Ohio, United States, 44309
      • Akron City Hospital
    • Cincinnati, Ohio, United States, 45219
      • Barrett Cancer Center, The University Hospital
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45236
      • Jewish Hospital of Cincinnati, Inc.
    • Cleveland, Ohio, United States, 44122
      • Meridia South Pointe Hospital
    • Cleveland, Ohio, United States, 44122
      • Mount Sinai Medical Center - Cleveland
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital - Ohio State University
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Kettering, Ohio, United States, 45429
      • CCOP - Dayton
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital Oncology Program
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • CCOP - St. Francis Hospital/Natalie Warren Bryant Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97201-3098
      • Oregon Cancer Center at Oregon Health Sciences University
    • Portland, Oregon, United States, 97213
      • CCOP - Columbia River Program
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105-1556
      • Lehigh Valley Hospital
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Network - Bethlehem
    • Danville, Pennsylvania, United States, 17822-2001
      • Penn State Geisinger Medical Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Cancer Institute
    • Pittsburgh, Pennsylvania, United States, 15240
      • Veterans Affairs Medical Center - Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15212-4772
      • Allegheny General Hospital
    • Reading, Pennsylvania, United States, 19612-6052
      • Reading Hospital and Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Warwick, Rhode Island, United States, 02886
      • Kent County Memorial Hospital - Rhode Island
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105-1080
      • CCOP - Sioux Community Cancer Consortium
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Veterans Affairs Medical Center - Memphis
    • Memphis, Tennessee, United States, 38117
      • CCOP - Baptist Cancer Institute
  • Texas
    • Dallas, Texas, United States, 75243
      • Medical Group of Texas
    • Houston, Texas, United States, 77025
      • Kelsey Seybold Clinic
    • Lackland Air Force Base, Texas, United States, 78236-5300
      • Wilford Hall - 59th Medical Wing
    • San Antonio, Texas, United States, 78284
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78284-7810
      • MBCCOP - South Texas Pediatric
    • Tyler, Texas, United States, 75710
      • University of Texas Health Center at Tyler
  • Utah
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Virginia Oncology Associates
    • Norfolk, Virginia, United States, 23507
      • Eastern Virginia Medical School
    • Richmond, Virginia, United States, 23298-0037
      • MBCCOP - Massey Cancer Center
    • Richmond, Virginia, United States, 23249
      • Veterans Affairs Medical Center - Richmond
    • Richmond, Virginia, United States, 23298-0037
      • Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia, Inc.
    • Salem, Virginia, United States, 24153
      • Veterans Affairs Medical Center - Salem
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98109
      • Puget Sound Oncology Consortium
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest
  • West Virginia
    • Parkersburg, West Virginia, United States, 26102
      • Camden-Clark Memorial Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • CCOP - Marshfield Medical Research and Education Foundation
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS: Histologically proven metastatic (stage IV) or locally advanced (stage IIIB) adenocarcinoma of the breast. Bidimensionally measurable disease. No active central nervous system (CNS) metastases. Brain metastases must be controlled for at least 3 months and have other sites of measurable disease. No carcinomatous meningitis. No lymphangitic lung metastases as the only site of metastatic disease. Hormone receptor status: Any estrogen or progesterone receptor status.

PATIENT CHARACTERISTICS: Age: 18 and over. Sex: Female. Menopausal status: Not specified. Performance status: Eastern Cooperative Oncology Group (ECOG) score range 0-2. Life expectancy: At least 6 months. Hematopoietic: Absolute neutrophil count at least 2,000/mm3. Platelet count at least 100,000/mm3. Hepatic: serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamic pyruvic transaminase (SGPT) no greater than 2.5 times upper limit of normal (ULN). Alkaline phosphatase no greater than 5 times ULN. Bilirubin no greater than ULN. No SGOT and/or SGPT greater than 1.5 times ULN if concomitant with alkaline phosphatase greater than 2.5 times ULN. Renal: Calcium no greater than 1.2 times ULN. Creatinine no greater than 1.5 times ULN. Cardiovascular:left ventricular ejection fraction (LVEF) at least institutional lower limit of normal on multiple gated acquisition scan (MUGA) or echocardiogram. No myocardial infarction within 6 months. No angina pectoris requiring antianginal medication. No history of congestive heart failure. No cardiac arrhythmias requiring medication. No vascular disease with documented cardiac function compromise No uncontrolled hypertension (diastolic greater than 100 mm Hg). Other: Not pregnant or nursing. Fertile patients must use effective barrier contraception. No diabetics with fasting blood sugar greater than 200 mg/dL. No peripheral neuropathy greater than grade 1. No psychosis or addictive disorders. No known hypersensitivity to E. coli-derived drugs.

PRIOR CONCURRENT THERAPY: Chemotherapy: No prior chemotherapy for metastatic breast cancer or non-breast cancer. At least 12 months since nontaxane containing adjuvant chemotherapy for primary tumor (in patients with metastatic disease). Prior adjuvant chemotherapy with anthracycline containing regimens allowed (provided total doxorubicin dose did not exceed 240 mg/m2). Endocrine therapy: At least 4 weeks since adjuvant hormone or hormone therapy for metastatic disease (at least 2 weeks for rapidly progressive disease). No concurrent hormonal birth control. Radiotherapy: At least 4 weeks since prior radiotherapy. Prior breast radiotherapy following lumpectomy allowed. No radiotherapy to greater than 30% of bone marrow. No prior left chest wall radiotherapy with anthracycline containing adjuvant chemotherapy. Surgery: Not specified.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Best over-all tumor response that occurs during 6 cycles of chemotherapy	18 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival	18 weeks
Time to first response	18 weeks
Time to progression	18 weeks
Duration of response	18 weeks
Completion of at least four cycles of chemotherapy	12 weeks
Toxicity profile	18 weeks

Collaborators and Investigators

• Sponsor: NSABP Foundation Inc
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Smith RE, Anderson SJ, Brown A, Scholnik AP, Desai AM, Kardinal CG, Lembersky BC, Mamounas EP. Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58. Clin Breast Cancer. 2002 Dec;3(5):333-40. doi: 10.3816/CBC.2002.n.036.

Study record dates

Study Major Dates

• Study Start: June 1, 1998
• Primary Completion (Actual): September 1, 2000
• Study Completion (Actual): December 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: June 26, 2003
• First Posted (Estimate): June 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 11, 2012
• Last Update Submitted That Met QC Criteria: December 10, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; stage IIIB breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: NSABP BP-58; NSABP-BP-58