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 volunteersQualifiers
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
Parallel
Treatments tested in this trial
Oxaliplatin intravenous
Drug85 mg/m² in intravenous. 1 cycle each 15 days
5 FU bolus
Drug5 fluorouracil : 400 mg/m² in bolus of 10 minutes (intravenous) following by 2400 mg/m² during 46 hours in intravenous
Folinic acid
Drug400 mg/m² in intravenous
Oxaliplatin intra-arteriel
Drug85 mg/m² in intra-arterial. 1 cycle each 15 days
Panitumumab
DrugOnly for patient RAS wild: 6 mg/Kg at each cycle in intravenous
Bevacizumab
Drug5 mg/kg at each cycle in intravenous
5 FU continuous
Drug2400 mg/m² intravenously over 46 hours
Irinotecan
Drug150 mg/m² intravenous
Treatment groups
Trial outcomes
Primary outcomes
progression-free survival
comparison of radiological/clinical progression free survival
Sponsors and contacts
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