Clinical trial NCT00268398: Combination Chemotherapy in Treating Patients With Colorectal Cancer and Resectable Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Metastatic Cancer
Chemotherapy
Keywords: adenocarcinoma of the colon
stage IV colon cancer
adenocarcinoma of the rectum
stage IV rectal cancer
resectable metastases
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
First posted: 2005-12-22
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: disease-free survival
timeFrame: 2-year
Secondary outcomes:
measure: Overall survival
timeFrame: 2-year, 3-year, 5-year
measure: Tolerability
timeFrame: 2-year
measure: Quality of life
timeFrame: 2-year
measure: Pharmacogenetics
timeFrame: 2-year
Other outcomes:
Locations:
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Avignon
country: France
facility: Hopital Duffaut
city: Beauvais
country: France
facility: C.H.G. Beauvais
city: Bordeaux
country: France
facility: Hopital Saint Andre
city: Boulogne Sur Mer
country: France
facility: Centre Hospitalier Docteur Duchenne
city: Boulogne-Billancourt
country: France
facility: Hopital Ambroise Pare
city: Briey
country: France
facility: Centre Hospitalier de Briey
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Chartres
country: France
facility: Hopital Louis Pasteur
city: Clichy
country: France
facility: Hopital Beaujon
city: Colombes Cedex
country: France
facility: Louis Mourier Hospital
city: Croix
country: France
facility: Clinique du Parc
city: Dijon
country: France
facility: Hopital Drevon
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: La Rochelle
country: France
facility: Hopital Saint - Louis
city: Libourne
country: France
facility: Hopital Robert Boulin
city: Lille
country: France
facility: Polyclinique Du Bois
city: Lille
country: France
facility: Centre Hospital Universitaire Hop Huriez
city: Lormont
country: France
facility: Polyclinique des Quatre Pavillons
city: Marseille
country: France
facility: Hopital Saint Joseph
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Montfermeil
country: France
facility: Centre Hospitalier Intercommunal Le Raincy - Montfermeil
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: CHU Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Tenon
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Reims
country: France
facility: Polyclinique De Courlancy
city: Saint Martin Boulogne
country: France
facility: Clinique Specialise du Littoral-Cote d'Opale
city: Sainte Foy Les Lyon
country: France
facility: Clinique Charcot
city: Senlis
country: France
facility: C.H. Senlis
city: Suresnes
country: France
facility: Hopital Foch
Study officials:
affiliation: Centre Hospital Universitaire Hop Huriez
name: Mohamed Hebbar, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.