Combination Chemotherapy in Treating Patients With Colorectal Cancer and Resectable Metastases (MIROX)

Essai De Phase III De Chimiotherapie Par FOLFOX 4 Ou Par Une Succession FOLFOX 7 - FOLFIRI Chez Des Patients Ayant Des Metastases Resecables D'Origine Colorectale - MIROX

PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work in treating patients with colorectal cancer and resectable metastases.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Chemotherapy; Metastatic Cancer
• Intervention / Treatment: Drug: oxaliplatin, folinic acid, fluorouracil; Drug: oxaliplatin, irinotecan, folinic acid, fluorouracil

Detailed Description

OBJECTIVES:

Primary

• Compare the 2-year disease-free survival rate in patients treated with these regimens.

Secondary

• Compare the overall survival of patients treated with these regimens.
• Compare the tolerability of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.
• Compare the objective response rate, postoperative complication rate, and transfusing rate in patients having metastasis surgery,
• Determine the pharmacogenetics of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter phase III study. Patients are stratified according to prior chemotherapy (perioperative vs postoperative), prior treatment (surgery only vs radiotherapy with or without surgery), and Blumgart score (0-1 vs 2-3 vs 4-5). Patients are randomized to 1 of 2 treatment arms.

• Arm I (FOLFOX 4): Patients receive FOLFOX 4 combination chemotherapy comprising oxaliplatin 85mg/m² IV over 2 hours, leucovorin calcium IV over 2 hours, fluorouracil IV bolus /15min and fluorouracil continuously over 22 hours on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.
• Arm II (FOLFOX 7 and FOLFIRI): Patients receive FOLFOX 7 combination chemotherapy comprising high-dose oxaliplatin 130mg/m² IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive FOLFIRI combination chemotherapy comprising irinotecan hydrochloride 180mg/m² IV over 30-90 minutes and leucovorin calcium and fluorouracil IV bolus /15min on day 1, and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients in both arms who have undergone prior resection of metastatic lesions may undergo surgery after 6 courses of chemotherapy or after chemotherapy is completed.

Quality of life is assessed at baseline and after courses 4, 8, and 12.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 284 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 284
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Avignon, France, 84000
    • Institut Sainte Catherine
  • Avignon, France, 84902
    • Hopital Duffaut
  • Beauvais, France, 60021
    • C.H.G. Beauvais
  • Bordeaux, France, 33075
    • Hopital Saint Andre
  • Boulogne Sur Mer, France, 62200
    • Centre Hospitalier Docteur Duchenne
  • Boulogne-Billancourt, France, F-92104
    • Hôpital Ambroise Paré
  • Briey, France, 54151
    • Centre Hospitalier de Briey
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Chartres, France, 28018
    • Hopital Louis Pasteur
  • Clichy, France, 92118
    • Hopital Beaujon
  • Colombes Cedex, France, 92701
    • Louis Mourier Hospital
  • Croix, France, 59170
    • Clinique du Parc
  • Dijon, France, 21000
    • Hopital Drevon
  • La Roche Sur Yon, France, F-85025
    • Centre Hospitalier departemental
  • La Rochelle, France, 17000
    • Hopital Saint - Louis
  • Libourne, France, 33500
    • Hôpital Robert Boulin
  • Lille, France, 59037
    • Centre Hospital Universitaire Hop Huriez
  • Lille, France, 59000
    • Polyclinique Du Bois
  • Lormont, France, 33310
    • Polyclinique des Quatre Pavillons
  • Marseille, France, 13008
    • Hôpital Saint Joseph
  • Metz, France, 57038
    • Hopital Notre-Dame de Bon Secours
  • Montfermeil, France, 93370
    • Centre Hospitalier Intercommunal Le Raincy - Montfermeil
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75651
    • CHU Pitié-Salpêtrière
  • Paris, France, 75970
    • Hôpital Tenon
  • Paris, France, 75571
    • Hôpital Saint Antoine
  • Pessac, France, 33604
    • Hopital Haut Leveque
  • Reims, France, F-51100
    • Polyclinique de Courlancy
  • Saint Martin Boulogne, France, 62280
    • Clinique Specialise du Littoral-Cote d'Opale
  • Sainte Foy Les Lyon, France, 69110
    • Clinique Charcot
  • Senlis, France, 60309
    • C.H. Senlis
  • Suresnes, France, 92151
    • Hopital Foch

Participation Criteria

Eligibility Criteria

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

Description

MAIN ELIGIBILITY CRITERIA

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum
• Resectable or resected metastatic disease,

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
• Bilirubin ≤ 2 times normal
• Creatinine ≤ 135 mmol/L or creatinine clearance ≥ 60 mL/min
• SGOT and SGPT ≤ 3 times ULN
• No peripheral neuropathy that affects normal functions
• No unresolved complications from prior surgery

PRIOR CONCURRENT THERAPY:

• At least 1 year since prior FOLFOX 4 or FOLFIRI regimen in the adjuvant setting
• No concurrent participation in another clinical trial
• Recovered from prior therapy

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
Active Comparator: FOLFOX4	Drug: oxaliplatin, folinic acid, fluorouracil; folinic acid 200 mg/m² (day 1&2) oxaliplatin 85 mg/m² (day 1) bolus 5FU 400 mg/m² (day 1&2) continuous 5FU 600mg/m² (day 1 to 2)
Experimental: FOLFOX7 followed by FOLFIRI	Drug: oxaliplatin, irinotecan, folinic acid, fluorouracil; FOLFOX7 folinic acid 400 mg/m² (day 1) oxaliplatin 130 mg/m² (day 1) continuous 5FU 3000mg/m² (day 1 to 2) FOLFIRI folinic acid 400 mg/m² (day 1) irinotecan 180 mg/m² (day 1) bolus 5FU 400 mg/m² (day 1) continuous 5FU 2400mg/m² (day 1 to 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
disease-free survival	2-year

Secondary Outcome Measures

Outcome Measure	Time Frame
Tolerability	2-year
Overall survival	2-year, 3-year, 5-year
Quality of life	2-year
Pharmacogenetics	2-year

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: Study Chair: Mohamed Hebbar, MD, Centre Hospital Universitaire Hop Huriez

Publications and helpful links

General Publications

• Hamidou Z, Chibaudel B, Hebbar M, Hug de Larauze M, Andre T, Louvet C, Brusquant D, Garcia-Larnicol ML, de Gramont A, Bonnetain F. Time to Definitive Health-Related Quality of Life Score Deterioration in Patients with Resectable Metastatic Colorectal Cancer Treated with FOLFOX4 versus Sequential Dose-Dense FOLFOX7 followed by FOLFIRI: The MIROX Randomized Phase III Trial. PLoS One. 2016 Jun 16;11(6):e0157067. doi: 10.1371/journal.pone.0157067. eCollection 2016.
• Hebbar M, Chibaudel B, Andre T, Mineur L, Smith D, Louvet C, Dutel JL, Ychou M, Legoux JL, Mabro M, Faroux R, Auby D, Brusquant D, Khalil A, Truant S, Hadengue A, Dalban C, Gayet B, Paye F, Pruvot FR, Bonnetain F, Landi B, Flesch M, Carola E, Martin P, Vaillant E, de Gramont A; Group Cooperateur Multidisciplinaire en Oncologie (GERCOR) Group. FOLFOX4 versus sequential dose-dense FOLFOX7 followed by FOLFIRI in patients with resectable metastatic colorectal cancer (MIROX): a pragmatic approach to chemotherapy timing with perioperative or postoperative chemotherapy from an open-label, randomized phase III trial. Ann Oncol. 2015 Feb;26(2):340-7. doi: 10.1093/annonc/mdu539. Epub 2014 Nov 17. Erratum In: Ann Oncol. 2015 May;26(5):1040. Taieb, J [removed]; Brucker, P [removed].

Study record dates

Study Major Dates

• Study Start: July 1, 2002
• Primary Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 20, 2005
• First Submitted That Met QC Criteria: December 20, 2005
• First Posted (Estimate): December 22, 2005

Study Record Updates

• Last Update Posted (Estimate): May 22, 2012
• Last Update Submitted That Met QC Criteria: May 21, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; resectable metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Hematinics; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Levoleucovorin; Folic Acid
• Other Study ID Numbers: CDR0000453815; GERCOR-C02-1; GERCOR-C02-1-MIROX; EU-20567; SANOFI-GERCOR-C02-1