Epirubicin and Docetaxel Combination (ET) or Epirubicin Followed by Docetaxel (E/T) for Node Negative (N0) High Risk Breast Cancer Patients

A Multicenter Randomized Phase III Study of Adjuvant Treatment With Epirubicin Followed by Docetaxel (E/T) Versus Epirubicin and Docetaxel Combination (ET) in High Risk Lymph Node Negative Breast Cancer Patients

The combination of taxanes, and especially docetaxel, with an anthracycline seems to be an important part of the chemotherapy regimens used in the adjuvant setting of patients with early-stage node-positive breast cancer patients. Whether sequential or concurrent administration of these drugs is preferable is not yet known, especially in patients with node-negative high risk tumors.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Epirubicin; Drug: Epirubicin; Drug: Docetaxel

• Study Type: Interventional
• Enrollment (Actual): 658
• Phase: Phase 3

Contacts and Locations

Study Locations

• Greece
  • Alexandroupolis, Greece
    • University Hospital of Alexandroupolis Dept. of Medical Oncology
  • Athens, Greece
    • 401 Military Hospital of Athens
  • Athens, Greece
    • Air Forces Military Hospital of Athens
  • Athens, Greece
    • "IASO" General Hospital of Athens
  • Athens, Greece
    • "Agios Savvas" Anticancer Hospital of Athens
  • Athens, Greece
    • "Laikon" General Hospital
  • Athens, Greece
    • "Marika Iliadis" Hospital of Athens
  • Athens, Greece
    • "Metaxa's" Anticancer Hospital of Pireas
  • Larissa, Greece
    • State General Hospital of Larissa
  • Thessaloniki, Greece
    • "Theagenion" Anticancer Hospital of Thessaloniki
  • Thessaloniki, Greece
    • "AXEPA" General Hospital of Thessaloniki
  • Crete
    • Heraklion, Crete, Greece, 71110
      • University Hospital of Heraklion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically or cytologically confirmed breast adenocarcinoma.
• Within 20-45 days after the surgical excision of the primary tumor with tumor-free operation margins; at least 10 axillary lymph nodes have to be removed.
• Absence of lymph node involvement after eclosion and hormone (E&H) staining and light microscopy evaluation.

• Premenopausal or postmenopausal women with at least one of the following tumor characteristics is required in order to characterize the tumor as high risk:

  • Estrogen receptor (ER) (-) and progesterone receptor (PR)(-);
  • Ki-67 + > 30%; Grade III; HER2 (3+) (after an amendment on 15.05.2008 women with HER2 (3+) were not included); Perineural infiltration or presence of tumor emboli in blood or lymph vessels.
• Postmenopausal women with tumors 1-2 cm are eligible if the tumor has at least 2 of the above mentioned high risk criteria.
• Premenopausal and postmenopausal women with tumors measuring > 2 cm are eligible irrespectively of the expression of the above adverse prognostic tumor criteria.
• Absence of any clinical or radiological evidence of local or metastatic disease.
• Age > 18 years.
• Performance status (WHO) < 3.
• Adequate bone marrow function (absolute neutrophil count > 1000/mm^3, platelet count > 100000/mm^3, hemoglobin > 9 gr/mm^3).
• Adequate liver (bilirubin < 1.5 times upper limit of normal and SGOT/SGPT < 2 times upper limit of normal) and renal function (creatinine < 2 mg/dl).
• Adequate cardiac function (LVEF > 50%).
• Negative pregnancy test.
• Informed consent.

Exclusion Criteria:

• Other invasive malignancy within the past 5 years except nonmelanoma skin cancer.
• Other concurrent uncontrolled illness that could affect compliance with the study.
• Psychiatric illness or social situation that would preclude study compliance.
• Pregnant or nursing women.
• History of allergic reaction attributed to docetaxel.
• Other concurrent investigational agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Docetaxel; Docetaxel at the dose of 75 mg/m2 intravenously (IV) every 3 weeks for 4 consecutive cycles; Other Names: Taxotere; Drug: Epirubicin; Epirubicin at the dose of 90 mg/m2 IV every 3 weeks for 4 consecutive cycles; Other Names: Farmorubicin; Drug: Epirubicin; Epirubicin at the dose of 75 mg/m2 IV every 3 weeks for 6 consecutive cycles; Other Names: Farmorubicin; Drug: Docetaxel; Docetaxel at the dose of 75 mg/m2 IV every 3 weeks for 6 consecutive cycles; Other Names: Taxotere
Experimental: 2	Drug: Docetaxel; Docetaxel at the dose of 75 mg/m2 intravenously (IV) every 3 weeks for 4 consecutive cycles; Other Names: Taxotere; Drug: Epirubicin; Epirubicin at the dose of 90 mg/m2 IV every 3 weeks for 4 consecutive cycles; Other Names: Farmorubicin; Drug: Epirubicin; Epirubicin at the dose of 75 mg/m2 IV every 3 weeks for 6 consecutive cycles; Other Names: Farmorubicin; Drug: Docetaxel; Docetaxel at the dose of 75 mg/m2 IV every 3 weeks for 6 consecutive cycles; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease-free interval between the two treatment arms	Five years

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of overall survival and safety between the two treatment arms	Five years

Collaborators and Investigators

• Sponsor: Hellenic Oncology Research Group
• Collaborators: University Hospital of Crete
• Investigators: Principal Investigator: Dimitris Mavrudis, MD, University Hospital of Heraklion Dept. of Medical Oncology

Study record dates

Study Major Dates

• Study Start: June 1, 2001
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: January 18, 2007
• First Submitted That Met QC Criteria: January 18, 2007
• First Posted (Estimate): January 19, 2007

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 19, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: High risk node negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Epirubicin
• Other Study ID Numbers: CT/01.04