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

• Status: Recruiting
• Trial end date: 2023-01-01
• Target enrollment: 0
• Participant gender: All

Summary

We hypothesized that intra-arterial gemcitabine/oxaliplatin administered as second-line treatment could strongly improve objective response rate at 4 months after inclusion in patient with non-metastatic unresectable intra-hepatic cholangiocarcinoma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Montpellier
• Collaborator: Federation Francophone de Cancerologie Digestive
• Treatments: Gemcitabine; Oxaliplatin

Criteria

Inclusion Criteria:

• Histologically-proven intrahepatic cholangiocarcinoma previously treated by first-line systemic therapy

• Absence of extra-hepatic metastasis or peritoneal carcinomatosis (as demonstrated by CT-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 a multidisciplinary 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 (even transfused 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 days preceding 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 those with hepatocholangiocarcinoma or a Klatskin tumor

• Patients who are eligible for surgical resection or liver transplantation

• Extra-hepatic metastases (Pulmonary micronodules <7mm without uptake on positron emission 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 first cycle 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 the study 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 serious underlying disorder likely to prevent the patient from receiving the treatment

• Pregnancy (beta-human chorionic gonadotropin positive), breast-feeding or the absence 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 to the active substance or excipients)

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

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

• 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 medical follow-up of the trial for geographical, social or psychological reasons

• Contraindication for the MRI : Pacemaker or neurosensorial stimulator or implantable defibrillator, cochlear implant, ferromagnetic foreign body similar to the nervous structure.