RecruitingPhase 2NCT03364530

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

Hepatic Arterial Infusion of Gemcitabine-oxaliplatin for Second-line Therapy in Non-metastatic Unresectable Intra-hepatic Cholangiocarcinoma: a Multicentric Single-arm Phase II Study

Sponsor

University Hospital, Montpellier

Enrollment

40 participants

Start Date

Jun 11, 2018

Study Type

INTERVENTIONAL

Conditions

Cholangiocarcinoma Non-resectable Non Metastatic

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria14

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 Criteria20

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.

Interventions

DRUGGemcitabine-Oxaliplatin Regimen

Vascularisation of hepatic tumors is almost exclusively provided by the hepatic artery. Gemcitabine and oxaliplatin have a high rate of hepatic extraction during the first passage, thus allowing the drugs to reach high intra-tumoral concentrations with low systemic toxicity.

PROCEDUREHepatic intra arterial chemotherapy

The implantation of a hepatic arterial catheter has now been mastered by interventional radiologists and makes it possible to increase the intra-tumoral concentration of the drugs and probably to limit their systemic toxicity. Very recently, we have reported that this combination in progressive IHC following systemic gemcitabine/oxaliplatin has led to partial responses and allowed certain patients to benefit from curative treatment. This suggests that the intra-arterial approach increases the efficacy of these 2 drugs. For locally-advanced IHC, such a loco-regional approach is worth exploring in this poor-prognosis tumor.