Chemotherapy Plus Surgery in Treating Women With Breast Cancer

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003013
First received: November 1, 1999
Last updated: September 16, 2013
Last verified: June 2000
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining surgery with chemotherapy may kill more tumor cells. It is not yet known which treatment regimen is more effective for breast cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of chemotherapy plus surgery in treating women who have breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: CMF regimen
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: fluorouracil
Drug: methotrexate
Drug: paclitaxel
Drug: tamoxifen citrate
Procedure: conventional surgery
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: European Cooperative Study of Chemotherapy and Surgery Comparing Adjuvant Doxorubicin Followed by CMF vs. Adjuvant Doxorubicin/Paclitaxel Followed by CMF vs. Primary Doxorubicin/Paclitaxel Followed by CMF in Women With Operable Breast Cancer and T>2 cm

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 450
Study Start Date: October 1996
Study Completion Date: March 2009
Detailed Description:

OBJECTIVES:

  • Evaluate whether 8 courses of primary chemotherapy before adequate surgery of breast tumor and locoregional radiotherapy plus tamoxifen for 5 years improves the disease-free and overall survival in women with operable breast carcinoma and tumor at diagnosis greater than 2 cm in diameter.
  • Assess whether, in the postoperative arms, the addition of paclitaxel to doxorubicin before CMF (cyclophosphamide, methotrexate, and fluorouracil) improves disease-free and overall survival in these patients.
  • Define the incidence of pathologic complete response (CR) induced by 8 courses of primary chemotherapy containing paclitaxel.
  • Assess whether a pathologic CR is an independent predictor of disease-free and overall survival.
  • Evaluate the effects of primary chemotherapy on the rate and quality of breast conserving surgery.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, tumor diameter at mammography, nuclear or histological grade, and estrogen/progesterone receptor status. Patients are randomized to one of three treatment arms.

  • Arm I: Patients receive doxorubicin IV over 15 minutes once every 3 weeks for 4 courses. Beginning 21 days after the last administration of doxorubicin, patients receive cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1 and 8. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  • Arms II and III: Patients receive doxorubicin IV over 15 minutes and paclitaxel IV over 3 hours once every 3 weeks for 4 courses. Beginning 21 days after the last administration of doxorubicin and paclitaxel, patients receive cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1 and 8. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

All patients have either mastectomy or breast conserving surgery; patients with unclear surgical margins may have second surgery (re-resection or total mastectomy) or radiotherapy. Lymph node axillary dissection is performed up to at least the second level. For patients in the 2 adjuvant arms (arms I and II), adjuvant chemotherapy starts by day 21 after surgery. For patients in the primary chemotherapy arm (arm III), surgery is performed by day 28 after the last course of chemotherapy or at resolution of all possible hematological or infective complications.

At the end of the combined surgery plus chemotherapy approach (i.e., after the last course of CMF (arms I and II) or after surgery (arm III)), patients enrolled after June 30, 2000 with estrogen or progesterone receptor positive disease receive oral tamoxifen daily for 5 years.

All patients who have breast conserving surgery receive postoperative irradiation within 4 weeks after completing chemotherapy and surgery (i.e., within 4 weeks from last dose of adjuvant chemotherapy (arms I and II) or from surgery (arm III)). All patients who have mastectomy and have pT4 disease must receive irradiation to the chest wall.

Patients are followed at 6, 12, 18, and 24 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 450 patients per arm will be accrued for this study within 5 years.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Unilateral carcinoma of the breast that has not been previously treated with standard therapies
  • Tumor greater than 2 cm in its maximum diameter as assessed by mammography, except:

    • No locally advanced disease, i.e., no tumor with direct extension to the chest wall or skin
    • No metastatic disease
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age:

  • 18 to 70

Sex:

  • Female

Menopausal status:

  • Not specified

Performance status:

  • Karnofsky 80-100%

Hematopoietic:

  • Granulocyte count at least 2,000/mm^3
  • Platelet count at least 150,000/mm^3

Hepatic:

  • Bilirubin within upper limits of normal (ULN)
  • Alkaline phosphatase no greater than 1.5 times ULN
  • AST no greater than 1.5 times ULN
  • No chronic active hepatitis

Renal:

  • Creatinine within ULN

Cardiovascular:

  • No prior atrial or ventricular arrhythmias
  • No history of congestive heart failure
  • No myocardial infarction within the past 6 months
  • No uncontrolled hypertension

Neurologic:

  • No pre-existing motor or sensory neuropathy greater than grade 1

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No active infection
  • No history of second malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior biologic therapy

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • No prior endocrine therapy

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • No prior surgery
  • No prior surgical biopsy of breast nodule
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003013

Locations
Austria
Kaiser Franz Josef Hospital
Vienna, Austria, A-1100
Czech Republic
Radiotherapy Institute
Ostrava-Poruba, Czech Republic, 70852
Estonia
University of Tartu
Tartu, Estonia, 51003
Germany
Frauenklinik Vom Roten Kreuz
Munich, Germany, 80637
Hungary
Semmelweis University
Budapest, Hungary, 1082
Uzsoki Hospital
Budapest, Hungary, 1145
Italy
Policlinico Monteluce
Perugia, Italy, 06122
Ospedale St. Santa Chiara
Pisa, Italy, 56100
Centro di Riferimento Oncologico - Aviano
Trento, Italy, 38100
Universita Degli Studi di Udine
Udine, Italy, 33100
Ospedale San Bortolo
Vicenza, Italy, 36100
Latvia
Latvian Cancer Center
Riga, Latvia, 1079
Poland
Regional Center of Oncology
Bydgoszcz, Poland, 85-796
Jagiellonian University
Krakow (Cracow), Poland, 31-826
Szpital Kliniczny NR 1
Poznan, Poland, PL-61-878
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Warsaw, Poland, 02-781
Russian Federation
Moscow Clinical Dispenser
Moscow, Russian Federation, 129128
N. A. Semashko Central Clinical Hospital
Moscow, Russian Federation, 129128
Russian Academy of Medical Sciences Cancer Research Center
Moscow, Russian Federation, 115478
Regional Oncology Clinic
Murmansk, Russian Federation, 183047
Petrov Research Institute of Oncology
Saint Petersburg, Russian Federation, 197758
Slovakia
St. Elizabeth Cancer Institute Hospital
Bratislava, Slovakia, SK-81250
Spain
Hospital de la Santa Cruz I Sant Pau
Barcelona, Spain, 08025
Hospital General Universitari Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Clinico Universitario - Malaga
Malaga, Spain, 29010
Instituto Valenciano De Oncologia
Valencia, Spain, 46009
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Study Chair: Gianni Bonadonna, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00003013     History of Changes
Other Study ID Numbers: CDR0000065593, INT-23/96, EU-97001
Study First Received: November 1, 1999
Last Updated: September 16, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Methotrexate
Liposomal doxorubicin
Doxorubicin
Tamoxifen
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites
Antimetabolites, Antineoplastic
Abortifacient Agents, Nonsteroidal

ClinicalTrials.gov processed this record on August 28, 2014