Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal Cancer Restricted to the Liver

Last updated: July 3, 2025
Sponsor: Federation Francophone de Cancerologie Digestive
Overall Status: Active - Recruiting

Phase

3

Condition

N/A

Treatment

Oxaliplatin intra-arteriel

Oxaliplatin intravenous

Bevacizumab

Clinical Study ID

NCT02885753
PRODIGE 49
  • Ages > 18
  • All Genders

Study Summary

Colorectal cancer is the 3rd most common cancer in France and the 2nd cause of death from cancer. Between 30 to 60% of patients develop limited or predominant liver metastases. Surgical resection of these metastases, only curative treatment is not immediately possible in 10-15% of cases. In unresectable patients, current palliative treatments are based on systemic chemotherapy associated or not with the targeted therapies (anti-EGFR (panitumumab), anti-VEGF (bevacizumab)). In this patient population, special attention was paid to intensified treatment regimens in order to improve their efficiency and improving the tumoral response rate, the intensity of the response and its earliness correlate with improved overall and progression-free survival.

The intra-arterial use of oxaliplatin coupled with IV chemotherapy has yielded OR levels of 64% in patients having survived one or more lines of chemotherapy IV and 62% in patients who have progressed on oxaliplatin IV. In addition, the HIA administration of oxaliplatin limits systemic and especially neurological toxicities, thanks to a greater hepatic clearance.

In conclusion, the combination of systemic chemotherapy, targeted therapy and HIAC with oxaliplatin has showed promising efficacy results associated with good tolerance from the first line onwards. Indeed, we can expect from the Phase II recent data, a control rate close to 100%, with high response rates associated with early maturity and depth responses as well as prolonged survival. However, to date, in the absence of randomized trial testing this combination, this strategy does not have sufficient evidence to be integrated in our routine practices, and HIAC remains limited to a few expert centers in treatment catch-up.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Histologically proven colorectal adenocarcinoma with hepatic metastasis(es)

  • At least one measurable hepatic metastasis according to the criteria RECIST v1.1

  • No other metastatic sites except lung nodules if number ≤ 3 and < 10 mm

  • RAS mutation status known (determination of KRAS mutation (exons 2,3 and 4) anddetermination of the NRAS mutation (exons 2,3 and 4))

  • Age ≥ 18

  • WHO ≤ 2 (Appendix 4)

  • No prior treatment by chemotherapy except perioperative or adjuvant chemotherapydiscontinued for more than 12 months

  • Life expectancy > 3 months

  • PNN > 1500/mm3, platelets > 100 000/mm3, Hb > 9 g/dLq

  • Bilirubin < 25 mmol/L, AST < 5x ULN, ALT < 5 x ULN, ALP < 5 x ULN, TP > 60%,proteinuria from 24H < 1 g

  • Creatinine clearance > 50 mL/min according to MDRD formula (Appendix 4)

  • Patient affiliated to a social security scheme

  • Patient information and signature of the informed consent

Exclusion

Exclusion Criteria:

  • Contraindications specific to the installation of a KTHIA: thrombosis of the hepaticartery, arterial vascular anatomy may compromise a secondary hepatic resection.

  • Patient immediately eligible for a curative therapy (surgical and/or percutaneous)after discussion in CPR

  • Following alterations in the 6 months prior to inclusion: myocardial infarction,angina, severe/unstable angina, coronary artery bypass surgery, congestive heartfailure NYHA class II, III or IV, stroke or transient ischemic attack

  • Hypertension not controlled by medical treatment (SBP > 140 mmHg and/or DBP> 90 mmHgwith blood pressure taken according to the diagram of the HAS)

  • A history of abdominal fistula, gastrointestinal perforation, intra-abdominalabscess or active gastrointestinal bleeding in the 6 months preceding the start oftreatment

  • Progressive gastroduodenal ulcer, wound or fractured bone

  • Abdominal or major extra-abdominal surgery (except diagnostic biopsy) or irradiationin the 4 weeks before starting the treatment

  • Transplant patients, HIV positive or other immune deficiency syndromes

  • Any progressive pathology not balanced over the past 6 months: hepatic failure,renal failure, respiratory failure

  • Peripheral neuropathy > 1

  • Patient with interstitial pneumonitis or pulmonary fibrosis

  • History of chronic diarrhea or inflammatory disease of the colon or rectum, orunresolved occlusion or sub-occlusion in symptomatic treatment

  • History of malignant pathologies during the past 5 years except basocellular skincarcinoma considered in complete remission or in situ cervical carcinoma, properlytreated

  • Patient already included in another clinical trial with an experimental molecule

  • Any known specific contraindication or allergy or hypersensitivity to the drugs usedin the study (cf RCP Appendix 7)

  • Known deficit in DPD

  • QT/QTc range > 450 msec for men and > 470 msec for women

  • K+ < LNL, Mg2+ < LNL, Ca2+ < LNL

  • Lack of effective contraception in patients (men and/or women) of childbearing age,pregnant or breastfeeding women, women of childbearing age not having had apregnancy test

  • Persons deprived of liberty or under supervision

  • Impossibility of undergoing medical monitoring during the trial for geographic,social or psychological reasons

Study Design

Total Participants: 348
Treatment Group(s): 8
Primary Treatment: Oxaliplatin intra-arteriel
Phase: 3
Study Start date:
December 01, 2016
Estimated Completion Date:
September 30, 2028

Connect with a study center

  • Hôpital Erasme

    Bruxelles,
    Belgium

    Active - Recruiting

  • CH D'Abbeville

    Abbeville CEDEX, 80142
    France

    Site Not Available

  • Centre Hospitalier du pays d'Aix

    Aix-en-Provence, 13616
    France

    Site Not Available

  • Hôpital Sud

    Amiens, 80054
    France

    Site Not Available

  • CHU - Hôtel Dieu

    Angers,
    France

    Active - Recruiting

  • Chu Hotel Dieu

    Angers,
    France

    Active - Recruiting

  • Institut de Cancérologie de l'Ouest

    Angers,
    France

    Active - Recruiting

  • Hôpital Privé d'Antony

    Antony,
    France

    Active - Recruiting

  • CH d'Auxerre

    Auxerre, 89000
    France

    Site Not Available

  • CH Henri Duffaut

    Avignon,
    France

    Site Not Available

  • Institut du cancer Avignon Provence

    Avignon,
    France

    Active - Recruiting

  • PRIVE - Sainte Catherine

    Avignon,
    France

    Active - Recruiting

  • Ch Cote Basque

    Bayonne,
    France

    Active - Recruiting

  • Clinique Belharra

    Bayonne,
    France

    Active - Recruiting

  • CH - Côte Basque

    Bayonne CEDEX, 64109
    France

    Site Not Available

  • CH de Beauvais

    Beauvais, 60021
    France

    Active - Recruiting

  • Centre Hospitalier

    Beauvais,
    France

    Site Not Available

  • CH Jean Minjoz

    Besançon, 25030
    France

    Site Not Available

  • Centre de Radiothérapie Pierre Curie

    Beuvry, 62660
    France

    Site Not Available

  • Institut Bergonié

    Bordeaux,
    France

    Active - Recruiting

  • PRIVE - Polyclinique Bordeaux Nord

    Bordeaux,
    France

    Active - Recruiting

  • Polyclinique Bordeaux Nord

    Bordeaux,
    France

    Active - Recruiting

  • Institut Bergonié

    Bordeaux CEDEX, 33076
    France

    Site Not Available

  • CMCO Côte d'Opale

    Boulogne-sur-Mer, 62222
    France

    Site Not Available

  • Hôpital Duchenne

    Boulogne-sur-Mer, 62321
    France

    Active - Recruiting

  • Centre François Baclesse

    Caen, 14076
    France

    Site Not Available

  • Infirmerie Protestante de Lyon

    Caluire-et-Cuire,
    France

    Active - Recruiting

  • PRIVE - Infirmerie Protestante de Lyon

    Caluire-et-Cuire, 69300
    France

    Active - Recruiting

  • CH Loire Vendée Océan

    Challans,
    France

    Site Not Available

  • CH William Morey

    Chalon-sur-Saône, 71100
    France

    Active - Recruiting

  • Hôpital Privé Sainte Marie

    Chalon-sur-Saône, 71100
    France

    Site Not Available

  • Centre Hospitalier Métropole Savoie

    Chambéry CEDEX, 73011
    France

    Site Not Available

  • Hôpital Louis Pasteur

    Chartres, 28018
    France

    Site Not Available

  • Hopitaux Civils de Colmar

    Colmar, 68024
    France

    Site Not Available

  • Clinique Saint Côme

    Compiègne CEDEX, 60204
    France

    Site Not Available

  • CH - Sud Francilien

    Corbeil-Essonnes,
    France

    Active - Recruiting

  • Centre Hospitalier Sud Francilien

    Corbeil-Essonnes,
    France

    Active - Recruiting

  • Hôpital Henri Mondor

    Créteil CEDEX, 94000
    France

    Site Not Available

  • CHU - Hôpital François Mitterand

    Dijon,
    France

    Active - Recruiting

  • Centre Georges-François Leclerc

    Dijon, 21079
    France

    Active - Recruiting

  • Chu Le Bocage

    Dijon,
    France

    Site Not Available

  • Institut de Cancérologie de Bourgogne - GRRECC

    Dijon, 21000
    France

    Active - Recruiting

  • CHU

    Grenoble,
    France

    Site Not Available

  • GHM Institut Daniel Hollard

    Grenoble CEDEX 1, 38028
    France

    Site Not Available

  • CH Marne La Vallée-Jossigny - Hôpital André Mignot

    Jossigny, 77600
    France

    Site Not Available

  • Ch - Chd Vendee

    La Roche Sur Yon,
    France

    Site Not Available

  • Chd Vendee

    La Roche-sur-Yon,
    France

    Active - Recruiting

  • Groupe Hospitalier de la Rochelle Re-Aunis

    La Rochelle,
    France

    Active - Recruiting

  • CHU Grenoble - Hôpital Albert Michallon

    La Tronche, 38700
    France

    Site Not Available

  • Hôpital André Mignot

    Le Chesnay, 78157
    France

    Site Not Available

  • CMC Les Ormeaux

    Le Havre, 76600
    France

    Site Not Available

  • Ch de Bicetre

    Le Kremlin-Bicêtre,
    France

    Site Not Available

  • Hôpital de Bicêtre

    Le Kremlin-Bicêtre, 94270
    France

    Active - Recruiting

  • CH du Mans

    Le Mans CEDEX 9, 72037
    France

    Site Not Available

  • Hôpital Francobritannique

    Levallois-Perret, 92300
    France

    Site Not Available

  • GH Nord Essone

    Longjumeau,
    France

    Site Not Available

  • Longjumeau,
    France

    Active - Recruiting

  • Hôpital du Scorff

    Lorient,
    France

    Active - Recruiting

  • CAC - Léon Bernard

    Lyon,
    France

    Active - Recruiting

  • Centre Léon Bérard

    Lyon,
    France

    Active - Recruiting

  • Hôpital Edouard Herriot

    Lyon, 69437
    France

    Active - Recruiting

  • Hôpital de la Croix Rousse

    Lyon,
    France

    Active - Recruiting

  • CH - Saint Joseph

    Marseille,
    France

    Active - Recruiting

  • Hôpital Européen

    Marseille,
    France

    Active - Recruiting

  • Hôpital Saint-Joseph

    Marseille,
    France

    Active - Recruiting

  • Institut Paoli Calmettes

    Marseille,
    France

    Site Not Available

  • PRIVE - Hôpital Européen

    Marseille,
    France

    Active - Recruiting

  • CHU La Timone

    Marseille CEDEX 5, 13385
    France

    Site Not Available

  • CH de Meaux

    Meaux, 77100
    France

    Site Not Available

  • Hôpital Belle Isle

    Metz, 57000
    France

    Site Not Available

  • Centre Hospitalier

    Montceau-les-Mines, 71300
    France

    Site Not Available

  • Centre Hospitalier

    Montélimar, 26216
    France

    Site Not Available

  • CHU - Hôtel Dieu

    Nantes,
    France

    Active - Recruiting

  • Centre d'Imagerie médicale du Confluent- IRIS GRIM

    Nantes,
    France

    Active - Recruiting

  • Chu Hotel Dieu

    Nantes,
    France

    Active - Recruiting

  • Hôpial Privé du Confluent Le Confluent Centre Catherine de Sienne

    Nantes,
    France

    Active - Recruiting

  • CHR

    Orleans,
    France

    Site Not Available

  • CHR La Source

    Orléans,
    France

    Site Not Available

  • CHU - Hôpital Européen George Pompidou

    Paris,
    France

    Active - Recruiting

  • CHU - Saint Louis

    Paris,
    France

    Active - Recruiting

  • Hôpital Cochin

    Paris,
    France

    Site Not Available

  • Hôpital Saint Antoine

    Paris, 75571
    France

    Active - Recruiting

  • Hôpital Saint Joseph

    Paris,
    France

    Active - Recruiting

  • Hôpital Saint Louis

    Paris,
    France

    Active - Recruiting

  • Institut Curie

    Paris, 75248
    France

    Active - Recruiting

  • PRIVE - Saint Joseph

    Paris,
    France

    Active - Recruiting

  • Paris Hôpital Européen Georges Pompidou

    Paris,
    France

    Active - Recruiting

  • CH - Centre Hospitalier de Pau

    Pau, 64046
    France

    Active - Recruiting

  • CH - Pau

    Pau,
    France

    Active - Recruiting

  • Centre Hospitalier

    Pau,
    France

    Active - Recruiting

  • Centre Hospitalier

    Pau CEDEX, 64046
    France

    Site Not Available

  • CH

    Perpignan,
    France

    Active - Recruiting

  • Centre Hospitalier Saint Jean

    Perpignan,
    France

    Active - Recruiting

  • CHU - Haut Lévêque

    Pessac,
    France

    Active - Recruiting

  • CHU Haut Lévêque

    Pessac,
    France

    Active - Recruiting

  • CH Lyon Sud

    Pierre-Bénite CEDEX, 69495
    France

    Site Not Available

  • CHU

    Poitiers,
    France

    Active - Recruiting

  • CHU La Milétrie

    Poitiers,
    France

    Active - Recruiting

  • CH René Dubois

    Pontoise, 95300
    France

    Site Not Available

  • CH Annecy Genevois

    Pringy, 74374
    France

    Site Not Available

  • Polyclinique Francheville

    Périgueux, 24004
    France

    Site Not Available

  • CHIC

    Quimper, 29000
    France

    Site Not Available

  • CHU Robert Debré

    Reims CEDEX, 51092
    France

    Site Not Available

  • CAC - Eugène Marquis

    Rennes,
    France

    Active - Recruiting

  • Centre Eugène Marquis

    Rennes,
    France

    Active - Recruiting

  • CHU de Pont Chaillou

    Rennes CEDEX 9, 35033
    France

    Site Not Available

  • CROME

    Ris-Orangis,
    France

    Site Not Available

  • Clinique Pasteur

    Ris-Orangis,
    France

    Site Not Available

  • Hôpital Drome Nord

    Romans-sur-Isère, 26100
    France

    Site Not Available

  • CHU

    Rouen,
    France

    Site Not Available

  • CHU Charles Nicolle

    Rouen,
    France

    Active - Recruiting

  • CHU Charles Nicolle

    Rouen CEDEX 01, 76031
    France

    Site Not Available

  • Saint Gregoire - Chp

    Saint Gregoire,
    France

    Site Not Available

  • Clinique Mutualiste de l'Estuaire - Cité Sanitaire

    Saint Nazaire, 44600
    France

    Site Not Available

  • Saint- Etienne Chu

    Saint- Etienne,
    France

    Site Not Available

  • CHP

    Saint-Grégoire,
    France

    Active - Recruiting

  • PRIVE - Saint Grégoire

    Saint-Grégoire,
    France

    Active - Recruiting

  • CAC - ICO Site René Gauducheau

    Saint-Herblain,
    France

    Active - Recruiting

  • Institut de cancérologie de l'Ouest

    Saint-Herblain,
    France

    Active - Recruiting

  • Centre Hospitalier de Saint Malo

    Saint-Malo, 35403
    France

    Site Not Available

  • CHU Saint-Etienne

    Saint-Priest-en-Jarez,
    France

    Active - Recruiting

  • CHU de Saint Etienne - Hôpital Nord

    Saint-Priest-en-Jarez, 42270
    France

    Active - Recruiting

  • Chu - Hopital Nord Chu Saint Etienne

    Saint-Priest-en-Jarez,
    France

    Active - Recruiting

  • Clinique Trenel

    Sainte Colombe, 69560
    France

    Site Not Available

  • CH

    Senlis CEDEX, 60309
    France

    Site Not Available

  • CH

    Soissons CEDEX, 02209
    France

    Site Not Available

  • Centre Paul Strauss

    Strasbourg, 67065
    France

    Site Not Available

  • Hôpital FOCH

    Suresnes,
    France

    Active - Recruiting

  • Maison de Santé Protestante de Bordeaux Bagatelle

    Talence,
    France

    Site Not Available

  • Hôpitaux du Leman

    Thonon-les-Bains, 74203
    France

    Site Not Available

  • Hia Sainte Anne

    Toulon,
    France

    Active - Recruiting

  • Hôpital Sainte Musse

    Toulon, 83000
    France

    Active - Recruiting

  • CHU - Rangueil

    Toulouse,
    France

    Active - Recruiting

  • Chu Toulouse Rangueil

    Toulouse,
    France

    Active - Recruiting

  • Clinique Pasteur

    Toulouse,
    France

    Site Not Available

  • CHU Nancy-Brabois

    Vandœuvre-lès-Nancy, 54511
    France

    Active - Recruiting

  • Institut de cancérologie de Lorraine

    Vandœuvre-lès-Nancy, 54519
    France

    Site Not Available

  • CAC - Gustave Roussy

    Villejuif,
    France

    Active - Recruiting

  • Hôpital Paul Brousse

    Villejuif,
    France

    Site Not Available

  • Institut Gustave Roussy

    Villejuif,
    France

    Active - Recruiting

  • CH - Kantonsspital Baden

    Baden,
    Switzerland

    Site Not Available

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