Cyclophosphamide, Methotrexate, and Fluorouracil, With or Without Epirubicin Hydrochloride, in Treating Women Who Have Undergone Surgery for Breast Cancer (Group III Closed to New Patients as of 12/7/2009)

August 1, 2013 updated by: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Adjuvant Treatment of Biologically Aggressive Breast Cancer (N-,N+1,3): Controlled Clinical Study

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, methotrexate, fluorouracil, and epirubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving cyclophosphamide together with methotrexate and fluorouracil before, after, or without epirubicin hydrochloride is more effective in treating patients with breast cancer that can be removed by surgery.

PURPOSE: This randomized phase III trial is comparing three regimens of cyclophosphamide given together with methotrexate and fluorouracil, with or without epirubicin hydrochloride, to see how well it works in treating women who have undergone surgery for breast cancer. (Group III was closed to new patients as of 12/7/2009.)

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the impact of adjuvant chemotherapy comprising epirubicin hydrochloride followed by cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, methotrexate, and fluorouracil followed by epirubicin hydrochloride versus cyclophosphamide, methotrexate, and fluorouracil on overall survival of patients with biologically aggressive, resectable, node-negative or node-positive breast cancer.

Secondary

  • To assess the disease-free survival and patterns of relapse in these patients.
  • To assess the tolerance to and toxicity of treatment in these patients.
  • To determine the quality of life of these patients.
  • To verify the effectiveness of these treatments in different subgroups of patients.
  • To collect, retrospectively, information on the expression of tumor suppressor gene p53, oncogene c-erbB-2, and bcl-2 protein involved in apoptosis. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to center, lymph node status (N0 vs N1-3), and estrogen receptor status (negative vs positive). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Beginning 4-6 weeks following surgery, patients receive epirubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1-8. Treatment repeats every 4 weeks for 4 courses.
  • Arm II: Beginning 4-6 weeks following surgery, patients receive cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1-8. Treatment repeats every 4 weeks for 4 courses. Patients then receive epirubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 4 courses.
  • Arm III (closed to accrual as of 12/7/2009): Beginning 4-6 weeks following surgery, patients receive cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1-8. Treatment repeats every 4 weeks for 6 courses.

Patients with estrogen receptor-positive disease receive tamoxifen daily for 5 years after completing chemotherapy.

After completion of study therapy, patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

Study Type

Interventional

Enrollment (Anticipated)

800

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed breast cancer

    • Underwent radical mastectomy, guadrantectomy, or tumorectomy with axillary node dissection within the past 4-6 weeks
    • Biologically aggressive disease

    • At least 10 lymph nodes removed

      • Node-negative (> 1 cm, or > 2 cm if histology is favorable, esp. tubular carcinoma and/or prevalent intraductal component > 50%) tumors OR node-positive (1-3) tumors, meeting the following criteria:

        • High thymidine-labeling index (> 3%)
        • Poorly differentiated tumor (grade III)
        • High S-phase fraction (> 10% by flow cytometry)
        • High Ki67/MIB1 expression (< 20%)
  • No bilateral breast cancer
  • No T4a, inoperable T4b, T4c, or T4d disease
  • Any estrogen receptor status (positive, negative, unknown)
  • No distant metastases

PATIENT CHARACTERISTICS:

  • Any menopause status
  • WBC ≥ 3,500/mL
  • ANC ≥ 1,500/mL
  • Platelet count ≥ 120,000/mL
  • AST and ALT ≤ 1.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 mg/mL
  • Bilirubin ≤ 1.5 times ULN
  • Not pregnant
  • Geographically accessible for follow-up
  • No prior breast cancer and/or other cancer except for carcinoma in situ of the cervix or basal cell skin cancer treated with radical intent
  • No significant alterations in cardiovascular function
  • No serious psychiatric disorders
  • No impaired renal or liver function

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival

Secondary Outcome Measures

Outcome Measure
Toxicity
Quality of life
Disease-free survival
Efficacy in subgroups of patients

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Investigators

  • Principal Investigator: Dino Amadori, MD, Morgagni-Pierantoni Ospedale

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 1997

Primary Completion (Anticipated)

December 1, 2010

Study Registration Dates

First Submitted

December 11, 2009

First Submitted That Met QC Criteria

December 11, 2009

First Posted (Estimate)

December 14, 2009

Study Record Updates

Last Update Posted (Estimate)

August 2, 2013

Last Update Submitted That Met QC Criteria

August 1, 2013

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRST-IBIS-03
  • CDR0000661068 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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