Adjuvant FEC Versus EP in Breast Cancer (MIG5) (MIG5)

Fluorouracil, Epirubicin and Cyclophosphamide Versus Concurrent Epirubicin and Paclitaxel in Node Positive Early Breast Cancer Patients: a Randomized, Phase III Trial of Gruppo Oncologico Nord-Ovest - Mammella Intergruppo Group

In this multicenter, randomized phase III trial, node positive early breast cancer patients are randomly assigned to receive either 6 cycles of FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, on day 1, every three weeks) or 4 cycles of EP (epirubicin 90 mg/m2 and paclitaxel 175 mg/m2, on day 1, every three weeks). The primary study endpoint is overall survival (OS). Secondary endpoints include toxicity and event free survival (EFS).

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Chemotherapy, Adjuvant
• Intervention / Treatment: Drug: 5-fluorouracil; Drug: epirubicin; Drug: cyclophosphamide; Drug: epirubicin; Drug: paclitaxel

Detailed Description

At the time the Gruppo Oncologico Nord-Ovest- Mammella Intergruppo trial 5 (GONO-MIG5) was designed in 1996, paclitaxel was known to have efficacy in patients with advanced breast cancer, but its role was still to be established in the adjuvant setting. Therefore the GONO-MIG5 trial was designed to compare a standard anthracycline-containing chemotherapy regimen, i.e. 5fluorouracil, epirubicin, ciclophosphamide (FEC), given for 6 cycles to a new regimen containing both epirubicin and paclitaxel (EP), given concurrently, for 4 cycles. This latter regimen was chosen on the basis of the results obtained in metastatic breast cancer patients, where the combination of doxorubicin and paclitaxel was associated with more than 90% of objective response . Only four cycles of the new regimen were planned since the expected toxicity, particularly the cardiotoxicity, was high, and a short treatment duration was hoped to be the best strategy to obtain a favourable balance between the toxicity and the expected high efficacy.

• Study Type: Interventional
• Enrollment (Actual): 1055
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Alba, Italy, 12051
    • Federico Castiglione
  • Cuneo, Italy, 12100
    • Ornella Garrone
  • Genoa, Italy, 16132
    • Lucia Del Mastro
  • Mantova, Italy, 46100
    • Giovanna Cavazzini
  • Pisa, Italy, 56100
    • Andrea Michelotti
  • Sassari, Italy, 07100
    • Tiziana Scotto
  • Torino, Italy, 10126
    • Antonio Durando
  • Torino, Italy, 10126
    • Saverio Danese

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women with histologically confirmed breast cancer who had undergone radical mastectomy or breast-conserving surgery in addition to full ipsilateral axillary lymph node dissection
• Lymph node-positive disease with less than 10 involved axillary lymph nodes
• Surgery performed not more than 5 weeks before randomization
• ECOG performance status 0
• Absolute neutrophil count ≥ 2,000/mm³
• WBC ≥ 3,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN
• Postoperative regional radiotherapy limited to the remaining breast admitted for patients who received breast-conserving surgery
• Written informed consent

Exclusion Criteria:

• Prior or concurrent ipsilateral or contralateral invasive breast carcinoma within the last 10 years
• Metastatic disease, including metastasis in the ipsilateral supraclavicular lymph nodes
• Prior chemotherapy or prior cytotoxic regimens or prior hormonal therapy
• Pregnant or nursing
• Other serious medical illness requiring medication, uncontrolled infections
• Other malignancy except adequately treated, cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin
• Recent myocardial infarction, congestive heart failure, or serious arrhythmia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FEC; 5-Fluorouracil 600 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, intravenously on day 1, every 21 days	Drug: 5-fluorouracil; 600 mg/m2 intravenously on day 1, every 21 days for six cycles; Drug: epirubicin; 60 mg/m2 intravenously on day 1, every 21 days for six cyles; Drug: cyclophosphamide; 600 mg/m2, intravenously on day 1, every 21 days for six cycles; Drug: epirubicin; 90 mg/m2 on day 1, every 21 days for four cycles
Active Comparator: EP; Epirubicin 90 mg/m2 and paclitaxel 175 mg/m2, 3-hour infusion on day 1, every 21 days	Drug: epirubicin; 60 mg/m2 intravenously on day 1, every 21 days for six cyles; Drug: epirubicin; 90 mg/m2 on day 1, every 21 days for four cycles; Drug: paclitaxel; 175 mg/m2, 3-hour infusion on day 1, every 21 days for four cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	estimated from the date of randomization to the date of death from any cause	within 11 years since the enrolment of the 1st patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
event free survival	from the date of randomization to the date of local recurrence, distant metastases, second primary cancer, or death from any cause	within 11 years since the enrolment of the 1st patient
toxicity as measured according to the World Health Organization Criteria		within the first 30 days after the end of chemotherapy

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• Investigators: Principal Investigator: Lucia Del Mastro, MD, IRCCS San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genoa

Study record dates

Study Major Dates

• Study Start: November 1, 1996
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: May 14, 2015
• First Submitted That Met QC Criteria: May 18, 2015
• First Posted (Estimate): May 21, 2015

Study Record Updates

• Last Update Posted (Estimate): May 21, 2015
• Last Update Submitted That Met QC Criteria: May 18, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: paclitaxel; adjuvant chemotherapy; early breast cancer; FEC
• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Fluorouracil; Epirubicin
• Other Study ID Numbers: OMI96.018