Liver Resection Versus Radio-chemotherapy-Transplantation for Hilar Cholangiocarcinoma

NCT ID: NCT02232932

Last Updated: 2021-11-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2024-09-30

Brief Summary

A prospective, open-label, randomised, multicentre, comparative study in two parallel groups comparing an interventional group with liver transplantation preceded by neoadjuvant radio-chemotherapy and a control group receiving conventional liver and bile duct resection.

The primary endpoint will be overall survival at 5 years in the intent-to-treat population. The secondary endpoint will be recurrence-free survival at 3 years evaluated by CT-scan and tumoral markers (Carcinoembryonic antigen (CAE) and cancer antigen (CA19.9)) in the intent-to-treat population.

The number of subjects necessary is 54 patients (27 x 2): this population will enable the demonstration of a significant difference is 5-year survival rates between the transplanted group and the resected group with a power of 80% and a first-species risk of 5%, under the hypothesis that these survival rates are 70% in the transplanted group and 30% in the resected group.

Detailed Description

The protocol will comprise a phase 1 during which the potential eligibility of patients (presenting with a resectable Klatskin - Excepted Type 1of Bismuth) will be assessed, based on clinical, biological and morphological data. After phases 1, the eligibility of the patient will be confirmed or not. In the context of the study, phase 2 will include the collection of blood samples as well as positon emission tomography (PET)-scan and upper endoscopic ultrasound (EUS) in order to rule out any obvious lymph node metastases. A short exploratory laparoscopy will also be performed in phase 2 to eliminate infra-clinic subcapsular liver metastases and peritoneal carcinomatosis. The randomization process will take place at the end of the phase 2, patients will be assigned into the transplantation arm (OLT) or the resection arm (RSX). During phase 3, patient will receive nutritional support and, if not done previously, a biliary drainage will be placed endoscopically. In the RSX arm (phase 3A), patients will undergo radical resection of the tumor (refer below technical details). Preoperative portal vein embolization may be necessary at this stage depending on the expected remnant liver volume, assessed by CT-scan volumetry. In the OLT arm (phase 3A), patients will receive neoadjuvant radiochemotherapy (External - 50 grays) following by liver transplantation (phase 4B). Before the fifth week after completion of radiochemotherapy, a staging laparotomy with local lymphadenectomy will be performed and patients will be put on the national waiting list in the absence of extra-hepatic disease, especially peritoneal seeding and lymph nodes involvement. A score exception will allowed a liver transplantation in the 3 months after staging laparotomy. During phase 5 the patient will be monitored postoperatively at the clinical, biological and morphological levels for 3 months. During phase 6, the patient will be followed clinically, biologically and morphologically for 5 years in order to detect any recurrence and in the context of standard clinical care.

Conditions

Cholangiocarcinoma

Keywords

Hilar cholangiocarcinoma; Liver transplantation; Radiochemotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAPECITABINE-Radiotherapy -Liver Transplantation

Neoadjuvant Radio-Chemotherapy (RC) and Liver Transplantation (LT)

Group Type: EXPERIMENTAL

CAPECITABINE-Radiotherapy -Liver Transplantation

Intervention Type: PROCEDURE

CAPECITABINE (800 mg/m2 twice a day during 5 weeks) + External Radiotherapy (50 grays during 5 weeks) then Liver transplantation

RESECTION

Liver resection

Group Type: ACTIVE_COMPARATOR

RESECTION

Intervention Type: PROCEDURE

Intent-to-treat R0 liver resection

Interventions

CAPECITABINE-Radiotherapy -Liver Transplantation

CAPECITABINE (800 mg/m2 twice a day during 5 weeks) + External Radiotherapy (50 grays during 5 weeks) then Liver transplantation

Intervention Type: PROCEDURE

RESECTION

Intent-to-treat R0 liver resection

Intervention Type: PROCEDURE

Other Intervention Names

Neoadjuvant Radio-Chemotherapy and Liver Transplantation; Liver Resection

Eligibility Criteria

Inclusion Criteria

• Patients (male or female) aged from 18 to 68 year-old, French
• Hilar cholangiocarcinoma histologically proved and/or highly suspected on hilar stenosis with mass syndrome from 0.1 cm to 3 cm
• Hilar cholangiocarcinoma type 2, type 3A, type 3B, type 4
• Patients considered as resectable (R0 resection) by liver resection including segment 1 and biliary confluence with or without vascular resection
• Patient potentially transplantable
• Patient affiliated to French Health Insurance
• Patient who had sign an informed consent

Exclusion Criteria

• Pregnant or breastfeeding woman
• Women of childbearing potential without an effective contraception method
• Radiotherapy contraindication
• Positive dosage of ImmunoglobulinsG4 (IgG4)
• dihydro-pyrimidine-dehydrogenase (DPD) total deficit
• Personal history of cancer in the last 5 five years (exclusion basocellular cellular carcinoma)
• Personal history of fluoropyrimidine hypersensibility
• Personal history of capecitabine hypersensibility
• Personal history of dihydro-pyrimidine-dehydrogenase deficit
• Polynuclear neutrophil < 1500 / ml
• Platelet rate < 100 000 / ml
• Severe leucopenia < 2000 / ml
• Severe liver failure (Factor V < 50%)
• Severe renal failure (Creatin clearance < 30 ml/min)
• Treatment by Sorivudine or its analogue as Brivudine
• Non controled diabetes mellitus and/or others severe co-morbidities (renal failure, severe and instable coronaropathy, severe risk factor of stroke, body mass index superior to 35)
• Proved histological cirrhosis
• Sclerosing cholangitis
• Intra and/or extra-hepatic metastases
• Hypereosinophilia and/or wirsung dilatation and/or mass of the pancreas head
• Hilar mass superior to 3 cm
• Duodenal invasion
• Patient under guardianship

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 68 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric VIBERT, MD

Role: PRINCIPAL_INVESTIGATOR

AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire, Villejuif, France

Locations

AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire

Villejuif, , France

Countries

France

Other Identifiers

P120106

Identifier Type: -

Identifier Source: org_study_id