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

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorFederation Francophone de Cancerologie Digestive

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

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))

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Oxaliplatin intravenous

    Drug

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

  • 5 FU bolus

    Drug

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

  • Folinic acid

    Drug

    400 mg/m² in intravenous

  • Oxaliplatin intra-arteriel

    Drug

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

  • Panitumumab

    Drug

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

  • Bevacizumab

    Drug

    5 mg/kg at each cycle in intravenous

  • 5 FU continuous

    Drug

    2400 mg/m² intravenously over 46 hours

  • Irinotecan

    Drug

    150 mg/m² intravenous

Treatment groups

348 Participants
are divided into 4 treatment groups
Group A: Experimental arm FOLFOX with oxaliplatin intraarterial + targeted therapy to RAS statusExperimental treatment 6 interventions
Group B: Reference arm FOLFOX with oxaliplatin intravenous + targeted therapy to RAS statusActive comparator 6 interventions
Group C: Experimental arm mFOLFIRINOX with oxaliplatin intraarterial + BevacizumabExperimental treatment 5 interventions
Group D: Reference arm mFOLFIRINOX with oxaliplatin intravenous + BevacizumabActive comparator 5 interventions

Trial outcomes

Primary outcomes

1

progression-free survival

comparison of radiological/clinical progression free survival

Time frame
24 months after randomization

Secondary outcomes

Other outcomes

Sponsors and contacts

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