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

• ClinicalTrials.gov Identifier: NCT02450058
• Recruitment Status: Completed
• First Posted: May 21, 2015
• Last Update Posted: May 21, 2015
• Sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• Information provided by (Responsible Party): Lucia Del Mastro,MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Chemotherapy, Adjuvant	Drug: 5-fluorouracil; Drug: epirubicin; Drug: cyclophosphamide; Drug: paclitaxel	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1055 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 1996
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: May 2012

Arms and Interventions

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
Active Comparator: EP; Epirubicin 90 mg/m2 and paclitaxel 175 mg/m2, 3-hour infusion on day 1, every 21 days	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

Outcome Measures

Primary Outcome Measures :

1. overall survival [ Time Frame: within 11 years since the enrolment of the 1st patient ]
   estimated from the date of randomization to the date of death from any cause

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Italy

Federico Castiglione

Alba, Italy, 12051

Ornella Garrone

Cuneo, Italy, 12100

Lucia Del Mastro

Genoa, Italy, 16132

Giovanna Cavazzini

Mantova, Italy, 46100

Andrea Michelotti

Pisa, Italy, 56100

Tiziana Scotto

Sassari, Italy, 07100

Antonio Durando

Torino, Italy, 10126

Saverio Danese

Torino, Italy, 10126

Sponsors and Collaborators

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

More Information

• Responsible Party: Lucia Del Mastro,MD, MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• ClinicalTrials.gov Identifier: NCT02450058
• Other Study ID Numbers: OMI96.018
• First Posted: May 21, 2015
• Last Update Posted: May 21, 2015
• Last Verified: May 2015

Keywords provided by Lucia Del Mastro,MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:

early breast cancer; adjuvant chemotherapy; FEC; paclitaxel

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Cyclophosphamide; Fluorouracil; Epirubicin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antimetabolites; Antimetabolites, Antineoplastic; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors