Hepatic Arterial Infusion of Gemcitabine-oxaliplatin for Second-line Therapy in Non-metastatic Unresectable Intra-hepatic Cholangiocarcinoma

Inclusion Criteria:

• Histologically-proven intrahepatic cholangiocarcinoma previously treated byfirst-line systemic therapy

• Absence of extra-hepatic metastasis or peritoneal carcinomatosis (as demonstrated byCT-scan)

• General health status : World Health Organization Performance Status = 0, 1

• Estimated life expectancy > 3 months

• Disease that is not suitable for resection with a curative intent, as validated by amultidisciplinary committee with at least one senior hepatic surgeon

• At least one measurable lesion according to RECIST 1.1 criteria

• Platelets ≥100,000/mm3, polynuclear neutrophils ≥ 2000/mm3 , hemoglobin 9g/dL (eventransfused patients can be included)

• Creatininemia < 1.5 mol/L

• Creatinine clearance > 30 mL/min

• Bilirubinemia ≤2 N (after biliary drainage if necessary)

• Aspartate and Alanine Transaminase ≤ 5 mol/L

• Reference hepatic MRI (according to the foreseen protocol) done during the 30 dayspreceding the 1st cycle of treatment

• Written informed consent

• National health insurance cover

Exclusion Criteria:

• Patients with cholangiocarcinoma of the gallbladder or common bile duct or thosewith hepatocholangiocarcinoma or a Klatskin tumor

• Patients who are eligible for surgical resection or liver transplantation

• Extra-hepatic metastases (Pulmonary micronodules <7mm without uptake on positronemission tomography are not a contra-indication)

• Presence of clinical ascites

• History of intra-arterial therapy or more than one line of systemic treatment

• Contra-indication or grade 3-4 allergy to any of the treatment drugs Gemcitabine,Oxaliplatin (notably myelosuppression developped before the beginning of the firstcycle of therapy, peripheral sensory neuropathy before the first cycle of therapy,severe renal failure)

• Grade 2 peripheral neuropathy

• Ongoing participation or participation within the 21 days prior to inclusion in thestudy in another therapeutic trial with an experimental drug

• Concomitant systemic treatment with immunotherapy, chemotherapy or hormone therapy

• Serious non-stabilized disease, active uncontrolled infection or other seriousunderlying disorder likely to prevent the patient from receiving the treatment

• Pregnancy (beta-human chorionic gonadotropin positive), breast-feeding or theabsence of effective contraception for women of child-bearing age

• Another cancer in the 5 years preceding or at the time of inclusion in the trial (except for in situ cervical cancer or basal cell carcinoma of the skin)

• Allergy or contra-indication to iodine contrast agents (thyrotoxicosis, allergy tothe active substance or excipients)

• Treatment with anticoagulants (heparin or AVK) that cannot be interrupted for 12hours

• Treatment with anti-platelets that cannot be interrupted for 5 days for aspirin orPlavix.

• Contra-indication for use of an intra-arterial approach (severe arteriopathy)

• Legal incapacity (persons in custody or under guardianship)

• Deprived of liberty Subject (by judicial or administrative decision)

• Impossibility to sign the informed consent document or to adhere to the medicalfollow-up of the trial for geographical, social or psychological reasons

• Contraindication for the MRI : Pacemaker or neurosensorial stimulator or implantabledefibrillator, cochlear implant, ferromagnetic foreign body similar to the nervousstructure.