Chemotherapies Associated With Targeted Therapies on the Resection Rate of Hepatic Metastases

Summary

The main objective is to compare resection rates (R0 or R1) for hepatic metastases in the experimental arm (tri chemotherapy plus targeted therapy) versus the control arm (bi chemotherapy plus targeted therapy); in both arms the targeted therapy is selected according to K-Ras status of the patient's tumor.

The secondary objectives are to evaluate the objective response rate (CR and PR) after 4 cycles of treatment, according the RECIST V1.1 evaluation scale.

* the rate of complete remission (CR) at 6 months after the last study treatment (hepatic surgery or last chemotherapy cycle).
* the specific rates of resection R0, R1, R2.
* the complete pathological response Rate,
* the relapse-free survival rate in (R0 or R1) resected patients,
* the response duration in non-resected patients,
* the toxicity according to CTC AE V4 scale except for the neurotoxicity that will be evaluated with the Levi scale,
* the post operative complications using the DINDO classification,
* the progression-free survival (PFS) and overall survival (OS).

The objectives of the biological study are:

* to evaluate tumor-related predictive factors such as somatic mutations (KRAS, BRAF, TP53) and genetic amplification related factors (EGFR),
* to evaluate patient-related predictive factors in connection with genetic polymorphisms (Fc gamma and VEGF receptors),
* to evaluate ADCC activity via immunohistochemistry in order to analyze the lympho free and progression-free survival,
* to study circulating of tumor cells as prognostic factor for metastatic colorectal cancer, non- resectable at presentation.

Conditions

• Colorectal Cancer

Interventions

DRUG

Oxaliplatin

85mg/m² over 120 mn every 2 weeks up to progression or toxicity

DRUG

Folinic Acid

400mg/m² over 120 mn every 2 weeks up to progression or toxicity

DRUG

5-FU

400mg/m² in bolus, then 2400mg/m² over 46 h every 2 weeks up to progression or toxicity

DRUG

Irinotecan

180mg/m² over 90 mn every 2 weeks up to progression or toxicity

DRUG

Irinotecan

150mg/m² over 30-90 mn every 2 weeks up to progression or toxicity

DRUG

Bevacizumab

5mg/kg over 90 mn every 2 weeks up to progression or toxicity

DRUG

Cetuximab

500mg/m² over 90 mn every 2 weeks up to progression or toxicity

Sponsors & Collaborators

• UNICANCER

  lead OTHER

Principal Investigators

• Marc YCHOU, Pr · Centre Val d'Aurelle

• Eric FRANCOIS, Dr · Centre Antoine Lacassagne, Nice

• Laurent MINEUR, Dr · Institut Ste Catherine-AVIGNON

• Olivier BOUCHE, Pr · CHU de Reims

• Driffa MOUSSATA, Dr · Centre hospitalier Lyon Sud-PIERRE BENITE

• Rosine GUIMBAUD, Pr · Centre hospitalier Rangueil-TOULOUSE

• Roger FAROUX, Dr · CHD Vendée -LA ROCHE SUR YON

• Karine BOUHIER-LEPORRIER, Dr · CHU Côte de Nacre-CAEN

• Alice GAGNAIRE, Dr · CHU Dijon - Hôp. Du Bocage

• Yves BECOUARN, Dr · Institut Bergonié Bordeaux

• François GHIRINGHELLI, Dr · Centre G. F. Leclerc-DIJON

• Rosine GUIMBAUD, Pr · Centre hospitalier Purpan-TOULOUSE

• Gaël DEPLANQUE, Dr · Centre Hospitalier Saint-Joseph-PARIS

• Julien FORESTIER, Dr · Hôpital Edouard Herriot-LYON

• Pascale MARIANI, Dr · Institut Curie Paris

• Jean-Louis LEGOUX, Dr · CHR d'Orléans - La Source

• Cédric LECAILLE, Dr · Polyclinique de Bordeaux Nord

• Marie-Pierre GALAIS, Dr · Centre François Baclesse-CAEN

• Philippe HOUYAU, Dr · Clinique Claude Bernard, Albi

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-02-28

Primary Completion

2015-12-31

Completion

2021-01-31

Countries

• France

Study Locations