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

NCT ID: NCT02885753

Last Updated: 2025-07-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

348 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-31

Study Completion Date

2028-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Colorectal Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

5 FU bolus

Intervention Type DRUG

5 fluorouracil : 400 mg/m² in bolus of 10 minutes (intravenous) following by 2400 mg/m² during 46 hours in intravenous

Folinic acid

Intervention Type DRUG

400 mg/m² in intravenous

Oxaliplatin intra-arteriel

Intervention Type DRUG

85 mg/m² in intra-arterial. 1 cycle each 15 days

Panitumumab

Intervention Type DRUG

Only for patient RAS wild: 6 mg/Kg at each cycle in intravenous

Bevacizumab

Intervention Type DRUG

5 mg/kg at each cycle in intravenous

5 FU continuous

Intervention Type DRUG

2400 mg/m² intravenously over 46 hours

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

Group Type ACTIVE_COMPARATOR

Oxaliplatin intravenous

Intervention Type DRUG

85 mg/m² in intravenous. 1 cycle each 15 days

5 FU bolus

Intervention Type DRUG

5 fluorouracil : 400 mg/m² in bolus of 10 minutes (intravenous) following by 2400 mg/m² during 46 hours in intravenous

Folinic acid

Intervention Type DRUG

400 mg/m² in intravenous

Panitumumab

Intervention Type DRUG

Only for patient RAS wild: 6 mg/Kg at each cycle in intravenous

Bevacizumab

Intervention Type DRUG

5 mg/kg at each cycle in intravenous

5 FU continuous

Intervention Type DRUG

2400 mg/m² intravenously over 46 hours

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

Group Type EXPERIMENTAL

Folinic acid

Intervention Type DRUG

400 mg/m² in intravenous

Oxaliplatin intra-arteriel

Intervention Type DRUG

85 mg/m² in intra-arterial. 1 cycle each 15 days

Bevacizumab

Intervention Type DRUG

5 mg/kg at each cycle in intravenous

5 FU continuous

Intervention Type DRUG

2400 mg/m² intravenously over 46 hours

Irinotecan

Intervention Type DRUG

150 mg/m² intravenous

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

Group Type ACTIVE_COMPARATOR

Oxaliplatin intravenous

Intervention Type DRUG

85 mg/m² in intravenous. 1 cycle each 15 days

Folinic acid

Intervention Type DRUG

400 mg/m² in intravenous

Bevacizumab

Intervention Type DRUG

5 mg/kg at each cycle in intravenous

5 FU continuous

Intervention Type DRUG

2400 mg/m² intravenously over 46 hours

Irinotecan

Intervention Type DRUG

150 mg/m² intravenous

Interventions

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Oxaliplatin intravenous

85 mg/m² in intravenous. 1 cycle each 15 days

Intervention Type DRUG

5 FU bolus

5 fluorouracil : 400 mg/m² in bolus of 10 minutes (intravenous) following by 2400 mg/m² during 46 hours in intravenous

Intervention Type DRUG

Folinic acid

400 mg/m² in intravenous

Intervention Type DRUG

Oxaliplatin intra-arteriel

85 mg/m² in intra-arterial. 1 cycle each 15 days

Intervention Type DRUG

Panitumumab

Only for patient RAS wild: 6 mg/Kg at each cycle in intravenous

Intervention Type DRUG

Bevacizumab

5 mg/kg at each cycle in intravenous

Intervention Type DRUG

5 FU continuous

2400 mg/m² intravenously over 46 hours

Intervention Type DRUG

Irinotecan

150 mg/m² intravenous

Intervention Type DRUG

Other Intervention Names

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Oxaliplatin IV 5 FU Folinic Acid IV Oxaliplatin IA Pani Beva 5 FU IRI

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julien TAIEB, MD-PhD

Role: PRINCIPAL_INVESTIGATOR

HEGP, Paris

Locations

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Hôpital Erasme

Brussels, , Belgium

Site Status RECRUITING

Chu Hotel Dieu

Angers, , France

Site Status RECRUITING

Institut de Cancérologie de l'Ouest

Angers, , France

Site Status RECRUITING

Hôpital Privé d'Antony

Antony, , France

Site Status RECRUITING

CH Henri Duffaut

Avignon, , France

Site Status NOT_YET_RECRUITING

Institut du cancer Avignon Provence

Avignon, , France

Site Status RECRUITING

Ch Cote Basque

Bayonne, , France

Site Status RECRUITING

Clinique Belharra

Bayonne, , France

Site Status RECRUITING

Centre Hospitalier

Beauvais, , France

Site Status NOT_YET_RECRUITING

Institut Bergonié

Bordeaux, , France

Site Status RECRUITING

Polyclinique Bordeaux Nord

Bordeaux, , France

Site Status RECRUITING

Infirmerie Protestante de Lyon

Caluire-et-Cuire, , France

Site Status RECRUITING

CH Loire Vendée Océan

Challans, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Sud Francilien

Corbeil-Essonnes, , France

Site Status RECRUITING

Chu Le Bocage

Dijon, , France

Site Status NOT_YET_RECRUITING

Chd Vendee

La Roche-sur-Yon, , France

Site Status RECRUITING

Groupe Hospitalier de la Rochelle Re-Aunis

La Rochelle, , France

Site Status RECRUITING

Ch de Bicetre

Le Kremlin-Bicêtre, , France

Site Status NOT_YET_RECRUITING

GH Nord Essone

Longjumeau, , France

Site Status NOT_YET_RECRUITING

Hôpital du Scorff

Lorient, , France

Site Status RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status RECRUITING

Hôpital de la Croix Rousse

Lyon, , France

Site Status RECRUITING

Hôpital Européen

Marseille, , France

Site Status RECRUITING

Hôpital Saint-Joseph

Marseille, , France

Site Status RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status NOT_YET_RECRUITING

Chu Hotel Dieu

Nantes, , France

Site Status RECRUITING

CHR La Source

Orléans, , France

Site Status NOT_YET_RECRUITING

Hôpital Cochin

Paris, , France

Site Status NOT_YET_RECRUITING

Hôpital Saint Joseph

Paris, , France

Site Status RECRUITING

Hôpital Saint Louis

Paris, , France

Site Status RECRUITING

Paris Hôpital Européen Georges Pompidou

Paris, , France

Site Status RECRUITING

Centre Hospitalier

Pau, , France

Site Status RECRUITING

Centre Hospitalier Saint Jean

Perpignan, , France

Site Status RECRUITING

CHU Haut Lévêque

Pessac, , France

Site Status RECRUITING

CHU La Milétrie

Poitiers, , France

Site Status RECRUITING

Centre Eugène Marquis

Rennes, , France

Site Status RECRUITING

Clinique Pasteur

Ris-Orangis, , France

Site Status NOT_YET_RECRUITING

CROME

Ris-Orangis, , France

Site Status NOT_YET_RECRUITING

CHU Charles Nicolle

Rouen, , France

Site Status RECRUITING

CHP

Saint-Grégoire, , France

Site Status RECRUITING

Institut de cancérologie de l'Ouest

Saint-Herblain, , France

Site Status RECRUITING

CHU Saint-Etienne

Saint-Priest-en-Jarez, , France

Site Status RECRUITING

Hôpital FOCH

Suresnes, , France

Site Status RECRUITING

Maison de Santé Protestante de Bordeaux Bagatelle

Talence, , France

Site Status NOT_YET_RECRUITING

Hia Sainte Anne

Toulon, , France

Site Status RECRUITING

Chu Toulouse Rangueil

Toulouse, , France

Site Status RECRUITING

Clinique Pasteur

Toulouse, , France

Site Status NOT_YET_RECRUITING

Hôpital Paul Brousse

Villejuif, , France

Site Status NOT_YET_RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Countries

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Belgium France

Central Contacts

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Sofia JOURDAN

Role: CONTACT

+33 (0)380393404

Marie MOREAU

Role: CONTACT

+33(0)3 80 39 32 36

Facility Contacts

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Gontran VERSET

Role: primary

0032 2 555 37 12

Antoine BOUVIER

Role: primary

02 41 35 35 03

Anne THIROT-BIDAULT

Role: primary

01 46 74 41 73

Adam VODNAR

Role: primary

Laurent MINEUR

Role: primary

04 90 27 61 81

Franck AUDEMAR

Role: primary

0559443722

Marjorie FAURE

Role: primary

0554614010

Hanifa AMMARGUELLAT

Role: primary

03 44 11 21 22

Simon PERNOT

Role: primary

05 56 33 32 78

Cédric LECAILLE

Role: primary

0556690681

Johannes HARTWIG

Role: primary

04 72 00 71 67

Margot LALY

Role: primary

02 51 44 61 68

Samy LOUAFI

Role: primary

0161693077

Sylvain MANFREDI

Role: primary

0380293750

Margot LALY

Role: primary

02 51 44 61 68

Valérie MOULIN

Role: primary

05 46 45 88 67

Lysiane MARTHEY

Role: primary

01 45 21 37 20

Samy LOUAFI

Role: primary

Florence LE ROY

Role: primary

02 97 06 95 20

Pauline ROCHEFORT

Role: primary

04 6985 60 23

Marielle GUILLET

Role: primary

04 26 73 28 88

Yves RINALDI

Role: primary

0380293750

Hervé PERRIER

Role: primary

0491808211

Elika LOIR

Role: primary

04 91 22 37 40

Yann TOUCHEFEU

Role: primary

02 40 08 31 52

Jean-Paul LAGASSE

Role: primary

02 38 51 47 04

Romain CORIAT

Role: primary

01 58 41 19 52

Nabil BABA HAMED

Role: primary

0144126888

Thomas APARICIO

Role: primary

01 42 49 95 97

Julien TAIEB

Role: primary

Mireille SIMON

Role: primary

05 59 92 49 83

Faiza KHEMISSA

Role: primary

0468616137

Denis SMITH

Role: primary

05 57 65 64 39

David TOUGERON

Role: primary

05 49 44 37 51

Samuel LE SOURD

Role: primary

02 99 25 31 96

Aroun Ali KHALFALLAH

Role: primary

01 69 25 68 17

Wassim KHODARI

Role: primary

01 69 02 10 65

Frédéric DI FIORE

Role: primary

02 32 88 64 56

Edith CARTON

Role: primary

02 90 09 44 66

Jean-Marc PHELIP

Role: primary

04 77 82 86 19

Asmahane BENMAZIANE TEILLET

Role: primary

01 46 25 28 64

Julien VERGNIOL

Role: primary

05 57 12 35 26

Caroline PRIEUX-KLOTZ

Role: primary

04 83 16 25 19

Rosine GUIMBAUD

Role: primary

05 61 32 27 41

Mathilde MARTINEZ

Role: primary

05 67 20 44 01

Mohamed BOUCHAHDA

Role: primary

Michel DUCREUX

Role: primary

0142114308

References

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Pernot S, Pellerin O, Mineur L, Monterymard C, Smith D, Lapuyade B, Gallois C, Khemissa Akouz F, De Baere T, Tougeron D, Thirot-Bidault A, Audemar F, Simon M, Lecaille C, Louafi S, Lepage C, Ducreux M, Taieb J. Phase III randomized trial comparing systemic versus intra-arterial oxaliplatin, combined with LV5FU2 +/- irinotecan and a targeted therapy, in the first-line treatment of metastatic colorectal cancer restricted to the liver (OSCAR): PRODIGE 49. Dig Liver Dis. 2022 Mar;54(3):324-330. doi: 10.1016/j.dld.2021.12.012. Epub 2022 Jan 11.

Reference Type DERIVED
PMID: 35027324 (View on PubMed)

Other Identifiers

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PRODIGE 49

Identifier Type: -

Identifier Source: org_study_id

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