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 (OSCAR)

July 3, 2025 updated by: Federation Francophone de Cancerologie Digestive

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

348

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
  • France
      • Angers, France
      • Angers, France
        • Recruiting
        • Institut de Cancerologie de L'Ouest
      • Antony, France
        • Recruiting
        • Hopital Prive d'Antony
        • Contact:
      • Avignon, France
        • Recruiting
        • Institut du Cancer Avignon Provence
        • Contact:
      • Avignon, France
      • Bayonne, France
      • Bayonne, France
      • Beauvais, France
      • Bordeaux, France
        • Recruiting
        • Institut Bergonie
        • Contact:
      • Bordeaux, France
        • Recruiting
        • Polyclinique Bordeaux Nord
        • Contact:
      • Caluire-et-Cuire, France
      • Challans, France
        • Not yet recruiting
        • CH Loire Vendée Océan
        • Contact:
      • Corbeil-Essonnes, France
        • Recruiting
        • Centre Hospitalier Sud Francilien
        • Contact:
      • Dijon, France
      • La Roche-sur-Yon, France
        • Recruiting
        • CHD Vendée
        • Contact:
      • La Rochelle, France
        • Recruiting
        • Groupe Hospitalier de la Rochelle Re-Aunis
        • Contact:
          • Valérie MOULIN
          • Phone Number: 05 46 45 88 67
      • Le Kremlin-Bicêtre, France
      • Longjumeau, France
        • Not yet recruiting
        • Gh Nord Essone
        • Contact:
          • Samy LOUAFI
      • Lorient, France
        • Recruiting
        • Hôpital du Scorff
        • Contact:
      • Lyon, France
      • Lyon, France
      • Marseille, France
        • Not yet recruiting
        • Institut Paoli Calmettes
        • Contact:
      • Marseille, France
        • Recruiting
        • Hopital Europeen
        • Contact:
      • Marseille, France
      • Nantes, France
      • Orléans, France
      • Paris, France
        • Recruiting
        • Hopital Saint Louis
        • Contact:
      • Paris, France
        • Not yet recruiting
        • Hopital Cochin
        • Contact:
      • Paris, France
        • Recruiting
        • Hopital Saint Joseph
        • Contact:
      • Paris, France
        • Recruiting
        • Paris Hôpital Européen Georges Pompidou
        • Contact:
      • Pau, France
      • Perpignan, France
        • Recruiting
        • Centre Hospitalier Saint Jean
        • Contact:
      • Pessac, France
      • Poitiers, France
      • Rennes, France
      • Ris-Orangis, France
        • Not yet recruiting
        • Clinique Pasteur
        • Contact:
      • Ris-Orangis, France
      • Rouen, France
      • Saint-Grégoire, France
      • Saint-Herblain, France
        • Recruiting
        • Institut de Cancerologie de L'Ouest
      • Saint-Priest-en-Jarez, France
      • Suresnes, France
        • Recruiting
        • Hopital Foch
        • Contact:
      • Talence, France
        • Not yet recruiting
        • Maison de Santé Protestante de Bordeaux Bagatelle
        • Contact:
      • Toulon, France
        • Recruiting
        • HIA Sainte Anne
        • Contact:
      • Toulouse, France
      • Toulouse, France
      • Villejuif, France
      • Villejuif, France
        • Not yet recruiting
        • Hopital Paul Brousse
        • Contact:
          • Mohamed BOUCHAHDA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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
Other Names:
  • 5 FU
Drug: Folinic acid
400 mg/m² in intravenous
Other Names:
  • Folinic Acid IV
Drug: Oxaliplatin intra-arteriel
85 mg/m² in intra-arterial. 1 cycle each 15 days
Other Names:
  • Oxaliplatin IA
Drug: Panitumumab
Only for patient RAS wild: 6 mg/Kg at each cycle in intravenous
Other Names:
  • Pani
Drug: Bevacizumab
5 mg/kg at each cycle in intravenous
Other Names:
  • Beva
Drug: 5 FU continuous
2400 mg/m² intravenously over 46 hours
Other Names:
  • 5 FU
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
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
Other Names:
  • 5 FU
Drug: Folinic acid
400 mg/m² in intravenous
Other Names:
  • Folinic Acid IV
Drug: Panitumumab
Only for patient RAS wild: 6 mg/Kg at each cycle in intravenous
Other Names:
  • Pani
Drug: Bevacizumab
5 mg/kg at each cycle in intravenous
Other Names:
  • Beva
Drug: 5 FU continuous
2400 mg/m² intravenously over 46 hours
Other Names:
  • 5 FU
Drug: Oxaliplatin intravenous
85 mg/m² in intravenous. 1 cycle each 15 days
Other Names:
  • Oxaliplatin IV
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
Drug: Folinic acid
400 mg/m² in intravenous
Other Names:
  • Folinic Acid IV
Drug: Oxaliplatin intra-arteriel
85 mg/m² in intra-arterial. 1 cycle each 15 days
Other Names:
  • Oxaliplatin IA
Drug: Bevacizumab
5 mg/kg at each cycle in intravenous
Other Names:
  • Beva
Drug: 5 FU continuous
2400 mg/m² intravenously over 46 hours
Other Names:
  • 5 FU
Drug: Irinotecan
150 mg/m² intravenous
Other Names:
  • IRI
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
Drug: Folinic acid
400 mg/m² in intravenous
Other Names:
  • Folinic Acid IV
Drug: Bevacizumab
5 mg/kg at each cycle in intravenous
Other Names:
  • Beva
Drug: 5 FU continuous
2400 mg/m² intravenously over 46 hours
Other Names:
  • 5 FU
Drug: Oxaliplatin intravenous
85 mg/m² in intravenous. 1 cycle each 15 days
Other Names:
  • Oxaliplatin IV
Drug: Irinotecan
150 mg/m² intravenous
Other Names:
  • IRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression-free survival
Time Frame: 24 months after randomization
comparison of radiological/clinical progression free survival
24 months after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federation Francophone de Cancerologie Digestive

Investigators

  • Principal Investigator: Julien TAIEB, MD-PhD, HEGP, Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2016

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2028

Study Registration Dates

First Submitted

August 23, 2016

First Submitted That Met QC Criteria

August 26, 2016

First Posted (Estimated)

August 31, 2016

Study Record Updates

Last Update Posted (Actual)

July 9, 2025

Last Update Submitted That Met QC Criteria

July 3, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRODIGE 49

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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