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

Who is this study for? Adult patients with liver metastases from colorectal cancer
What treatments are being studied? 5 Fu+Folinic Acid+Oxaliplatin intra-arterial+Panitumumab+Bevacizumab
Status: Recruiting
Location: See all (49) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
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
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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) and determination of the NRAS mutation (exons 2,3 and 4))

• Age ≥ 18

• WHO ≤ 2 (Appendix 4)

• No prior treatment by chemotherapy except perioperative or adjuvant chemotherapy discontinued 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

Locations
Other Locations
Belgium
Hôpital Erasme
RECRUITING
Brussels
France
Chu Hotel Dieu
RECRUITING
Angers
Institut de Cancérologie de l'Ouest
RECRUITING
Angers
Hôpital Privé d'Antony
RECRUITING
Antony
CH Henri Duffaut
NOT_YET_RECRUITING
Avignon
Institut du cancer Avignon Provence
RECRUITING
Avignon
Ch Cote Basque
RECRUITING
Bayonne
Clinique Belharra
RECRUITING
Bayonne
Centre Hospitalier
NOT_YET_RECRUITING
Beauvais
Institut Bergonié
RECRUITING
Bordeaux
Polyclinique Bordeaux Nord
RECRUITING
Bordeaux
Infirmerie Protestante de Lyon
RECRUITING
Caluire-et-cuire
CH Loire Vendée Océan
NOT_YET_RECRUITING
Challans
Centre Hospitalier Sud Francilien
RECRUITING
Corbeil-essonnes
Chu Le Bocage
NOT_YET_RECRUITING
Dijon
Chd Vendee
RECRUITING
La Roche-sur-yon
Groupe Hospitalier de la Rochelle Re-Aunis
RECRUITING
La Rochelle
Ch de Bicetre
NOT_YET_RECRUITING
Le Kremlin-bicêtre
GH Nord Essone
NOT_YET_RECRUITING
Longjumeau
Hôpital du Scorff
RECRUITING
Lorient
Centre Léon Bérard
RECRUITING
Lyon
Hôpital de la Croix Rousse
RECRUITING
Lyon
Hôpital Européen
RECRUITING
Marseille
Hôpital Saint-Joseph
RECRUITING
Marseille
Institut Paoli Calmettes
NOT_YET_RECRUITING
Marseille
Chu Hotel Dieu
RECRUITING
Nantes
CHR La Source
NOT_YET_RECRUITING
Orléans
Hôpital Cochin
NOT_YET_RECRUITING
Paris
Hôpital Saint Joseph
RECRUITING
Paris
Hôpital Saint Louis
RECRUITING
Paris
Paris Hôpital Européen Georges Pompidou
RECRUITING
Paris
Centre Hospitalier
RECRUITING
Pau
Centre Hospitalier Saint Jean
RECRUITING
Perpignan
CHU Haut Lévêque
RECRUITING
Pessac
CHU La Milétrie
RECRUITING
Poitiers
Centre Eugène Marquis
RECRUITING
Rennes
Clinique Pasteur
NOT_YET_RECRUITING
Ris-orangis
CROME
NOT_YET_RECRUITING
Ris-orangis
CHU Charles Nicolle
RECRUITING
Rouen
CHP
RECRUITING
Saint-grégoire
Institut de cancérologie de l'Ouest
RECRUITING
Saint-herblain
CHU Saint-Etienne
RECRUITING
Saint-priest-en-jarez
Hôpital FOCH
RECRUITING
Suresnes
Maison de Santé Protestante de Bordeaux Bagatelle
NOT_YET_RECRUITING
Talence
Hia Sainte Anne
RECRUITING
Toulon
Chu Toulouse Rangueil
RECRUITING
Toulouse
Clinique Pasteur
NOT_YET_RECRUITING
Toulouse
Hôpital Paul Brousse
NOT_YET_RECRUITING
Villejuif
Institut Gustave Roussy
RECRUITING
Villejuif
Contact Information
Primary
Sofia JOURDAN
sofia.jourdan@u-bourgogne.fr
+33 (0)380393404
Backup
Marie MOREAU
marie.moreau@u-bourgogne.fr
+33(0)3 80 39 32 36
Time Frame
Start Date: 2016-12
Estimated Completion Date: 2028-09
Participants
Target number of participants: 348
Treatments
Experimental: Experimental arm FOLFOX with oxaliplatin intraarterial + targeted therapy to RAS status
Panitumumab (6 mg/kg if RAS wild) or Bevacizumab (5 mg/Kg if RAS mutated) Oxaliplatin (85 mg/m²) intraarterially Folinic Acid (400 mg/m²) intravenously 5Fu: 400 mg/m² in bolus of 10 minutes 5Fu: 2400 mg/m² intravenously over 46 hours
Active_comparator: Reference arm FOLFOX with oxaliplatin intravenous + targeted therapy to RAS status
Panitumumab (6 mg/kg if RAS wild) or Bevacizumab (5 mg/Kg if RAS mutated) Oxaliplatin (85 mg/m²) intravenously Folinic Acid (400 mg/m²) intravenously 5Fu: 400 mg/m² in bolus of 10 minutes 5Fu: 2400 mg/m² intravenously over 46 hours
Experimental: Experimental arm mFOLFIRINOX with oxaliplatin intraarterial + Bevacizumab
Bevacizumab (5 mg/Kg) Oxaliplatin (85 mg/m²) intraarterially Irinotecan (150 mg/m²) intravenously Folinic Acid (400 mg/m²) intravenously 5Fu: 2400 mg/m² intravenously over 46 hours
Active_comparator: Reference arm mFOLFIRINOX with oxaliplatin intravenous + Bevacizumab
Bevacizumab (5 mg/Kg) Oxaliplatin (85 mg/m²) intravenously Irinotecan (150 mg/m²) intravenously Folinic Acid (400 mg/m²) intravenously 5Fu: 2400 mg/m² intravenously over 46 hours
Authors
Corinne COUTEAU, Eric RAYMOND, Tanguy ROHOU, Véronique GIRRE, Charles MASTIER, Frédéric DOUANE, Frank PRIOU, Thomas APARICIO, Clémence TOULLEC, Aymeric GUIBAL, Sylvie KIRSCHER, Aurélie FERRU, Laurent BALARDY, Nadim FARES, Yann TOUCHEFEU, Abdennaceur DHAHRI, Jérôme CHAMOIS, Nathalie BAIZE, Antoine HOLLEBECQUE, Pierre GUIBERT, Géraldine PERKINS, Céline LEPERE, Eric TERREBONNE, Clélia COUTZAC, Matthieu SCHNEE, Julien TAIEB, Jean Marc REGIMBEAU, Yves RINALDI, Nelson LOURENCO, Samy LOUAFI, Denis SMITH, Astrid LIEVRE, Paul GIROT, Françoise DESSEIGNE, Michel DUCREUX, Cédric LECAILLE, Philippe DEBOURDEAU, Hélène SENELLART, Valérie BOIGE, Hervé PERRIER, Stéphane VELASCO, Violaine RANDRIAN, Olivier PELLERIN, Laurent MINEUR, Rosine GUIMBAUD, Aziz ZAANAN, David MALKA, Estelle CAUCHIN, Bruno CHAUFFERT, Dominique LUET, Laurent MIGLIANICO, Judith RAIMBOURG, Laurence CROUZET, Anaïs BODERE, Romaric LOFFROY, Matthieu SARABI, David TOUGERON, Antoine HAMY, Christophe PERRET, Morgane AMIL, Bruno LAPUYADE, Caroline CARAMELLA, Philippe OTAL, Sandrine HIRET, Véronique GUERIN-MEYER, Xavier ARTIGNAN, Margarida MATIAS, Julien EDELINE, Simon PERNOT, Marc PRACHT, Pascal BURTIN, Romuald LE SCODAN, Jean-Paul JOLY, Stefanie PEDERIVA, Caroline PRIEUX-KLOTZ, Jean-François RAMEE, Muriel CUILLERON, Jean-Louis JOUVE, Eric DE KERVILER, Faiza KHEMISSA AKOUZ, Anne-Laure POINTET, Jean-Marc PHELIP, Nabil BABA-HAMED, Jean-Luc RAOUL, Jean-Marc GORNET, François-Xavier CAROLI-BOSC, Antonio NOCITO, Jean-Frédéric BLANC
Related Therapeutic Areas
Sponsors
Leads: Federation Francophone de Cancerologie Digestive

This content was sourced from clinicaltrials.gov