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

Colorectal Neoplasms Clinical Trial

— OSCAR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02885753
• Other study ID #: PRODIGE 49
• Status: Recruiting
• Phase: Phase 3
• Start date: December 2016
• Est. completion date: September 2027

Study information

• Verified date: August 2023
• Source: Federation Francophone de Cancerologie Digestive
• Contact: Sofia JOURDAN
• Phone: +33 (0)380393404
• Email: sofia.jourdan[@]u-bourgogne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 348
• Est. completion date: September 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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) 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

Exclusion Criteria:

• Contraindications specific to the installation of a KTHIA: thrombosis of the hepatic artery, 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 heart failure NYHA class II, III or IV, stroke or transient ischemic attack

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

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

• Progressive gastroduodenal ulcer, wound or fractured bone

• Abdominal or major extra-abdominal surgery (except diagnostic biopsy) or irradiation in 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, or unresolved occlusion or sub-occlusion in symptomatic treatment

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

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

• Any known specific contraindication or allergy or hypersensitivity to the drugs used in 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 a pregnancy test

• Persons deprived of liberty or under supervision

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

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• Oxaliplatin intravenous
85 mg/m² in intravenous. 1 cycle each 15 days
• 5 FU bolus
5 fluorouracil : 400 mg/m² in bolus of 10 minutes (intravenous) following by 2400 mg/m² during 46 hours in intravenous
• Folinic acid
400 mg/m² in intravenous
• Oxaliplatin intra-arteriel
85 mg/m² in intra-arterial. 1 cycle each 15 days
• Panitumumab
Only for patient RAS wild: 6 mg/Kg at each cycle in intravenous
• Bevacizumab
5 mg/kg at each cycle in intravenous
• 5 FU continuous
2400 mg/m² intravenously over 46 hours
• Irinotecan
150 mg/m² intravenous

Locations

Country	Name	City	State
France	CH D'Abbeville	Abbeville CEDEX
France	Centre Hospitalier du pays d'Aix	Aix-en-Provence
France	Hôpital Sud	Amiens
France	CHU - Hôtel Dieu	Angers
France	Hôpital Privé d'Antony	Antony
France	CH d'Auxerre	Auxerre
France	PRIVE - Sainte Catherine	Avignon
France	CH - Côte Basque	Bayonne CEDEX
France	CH de Beauvais	Beauvais
France	CH Jean Minjoz	Besançon
France	Centre de Radiothérapie Pierre Curie	Beuvry
France	PRIVE - Polyclinique Bordeaux Nord	Bordeaux
France	Institut Bergonié	Bordeaux CEDEX
France	CMCO Côte d'Opale	Boulogne-sur-Mer
France	Hôpital Duchenne	Boulogne-sur-Mer
France	Centre François Baclesse	Caen
France	PRIVE - Infirmerie Protestante de Lyon	Caluire-et-Cuire
France	CH William Morey	Chalon-sur-Saône
France	Hôpital Privé Sainte Marie	Chalon-sur-Saône
France	Centre Hospitalier Métropole Savoie	Chambéry CEDEX
France	Hôpital Louis Pasteur	Chartres
France	Hopitaux Civils de Colmar	Colmar
France	Clinique Saint Côme	Compiègne CEDEX
France	CH - Sud Francilien	Corbeil-Essonnes
France	Hôpital Henri Mondor	Créteil CEDEX
France	Centre Georges-François Leclerc	Dijon
France	CHU - Hôpital François Mitterand	Dijon
France	Institut de Cancérologie de Bourgogne - GRRECC	Dijon
France	GHM Institut Daniel Hollard	Grenoble CEDEX 1
France	CH Marne La Vallée-Jossigny - Hôpital André Mignot	Jossigny
France	Ch - Chd Vendee	La Roche Sur Yon
France	CHU Grenoble - Hôpital Albert Michallon	La Tronche
France	Hôpital André Mignot	Le Chesnay
France	CMC Les Ormeaux	Le Havre
France	Hôpital de Bicêtre	Le Kremlin-Bicêtre
France	CH du Mans	Le Mans CEDEX 9
France	Hôpital Francobritannique	Levallois-Perret
France	CAC - Léon Bernard	Lyon
France	Hôpital Edouard Herriot	Lyon
France	CH - Saint Joseph	Marseille
France	PRIVE - Hôpital Européen	Marseille
France	CHU La Timone	Marseille CEDEX 5
France	CH de Meaux	Meaux
France	Hôpital Belle Isle	Metz
France	Centre Hospitalier	Montceau-les-Mines
France	Centre Hospitalier	Montélimar
France	Centre d'Imagerie médicale du Confluent- IRIS GRIM	Nantes
France	CHU - Hôtel Dieu	Nantes
France	Hôpial Privé du Confluent Le Confluent Centre Catherine de Sienne	Nantes
France	CHR	Orleans
France	CHU - Hôpital Européen George Pompidou	Paris
France	CHU - Saint Louis	Paris
France	Hôpital Cochin	Paris
France	Hôpital Saint Antoine	Paris
France	Institut Curie	Paris
France	PRIVE - Saint Joseph	Paris
France	CH - Centre Hospitalier de Pau	Pau
France	CH - Pau	Pau
France	Polyclinique Francheville	Périgueux
France	CH	Perpignan
France	CHU - Haut Lévêque	Pessac
France	CH Lyon Sud	Pierre-Bénite CEDEX
France	CHU	Poitiers
France	CH René Dubois	Pontoise
France	CH Annecy Genevois	Pringy
France	CHIC	Quimper
France	CHU Robert Debré	Reims CEDEX
France	CAC - Eugène Marquis	Rennes
France	CHU de Pont Chaillou	Rennes CEDEX 9
France	Hôpital Drome Nord	Romans-sur-Isère
France	CHU Charles Nicolle	Rouen CEDEX 01
France	Clinique Mutualiste de l'Estuaire - Cité Sanitaire	Saint Nazaire
France	PRIVE - Saint Grégoire	Saint-Grégoire
France	CAC - ICO Site René Gauducheau	Saint-Herblain
France	Centre Hospitalier de Saint Malo	Saint-Malo
France	Chu - Hopital Nord Chu Saint Etienne	Saint-Priest-en-Jarez
France	CHU de Saint Etienne - Hôpital Nord	Saint-Priest-en-Jarez
France	Clinique Trenel	Sainte Colombe
France	CH	Senlis CEDEX
France	CH	Soissons CEDEX
France	Centre Paul Strauss	Strasbourg
France	Hôpitaux du Leman	Thonon-les-Bains
France	Hôpital Sainte Musse	Toulon
France	CHU - Rangueil	Toulouse
France	CHU Nancy-Brabois	Vandœuvre-lès-Nancy
France	Institut de cancérologie de Lorraine	Vandœuvre-lès-Nancy
France	CAC - Gustave Roussy	Villejuif
France	Hôpital Paul BROUSSE	Villejuif
Switzerland	CH - Kantonsspital Baden	Baden

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Countries where clinical trial is conducted

France,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival	comparison of radiological/clinical progression free survival	24 months after randomization