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Liver Resection Versus Radio-chemotherapy-Transplantation for Hilar Cholangiocarcinoma (TRANSPHIL)

Primary Purpose

Cholangiocarcinoma

Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
CAPECITABINE-Radiotherapy -Liver Transplantation
RESECTION
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cholangiocarcinoma focused on measuring Hilar cholangiocarcinoma, Liver transplantation, Radiochemotherapy

Eligibility Criteria

18 Years - 68 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CAPECITABINE-Radiotherapy -Liver Transplantation

RESECTION

Arm Description

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

Liver resection

Outcomes

Primary Outcome Measures

Overall survival
To demonstrate the superiority, in terms of 5-year survival, of liver transplantation (TH) preceded by neoadjuvant chemoradiotherapy on the radical resection of Klatskin tumors considered resectable

Secondary Outcome Measures

Recurrence free survival
3-year recurrence-free survival assessed by CT and markers

Full Information

First Posted
August 6, 2014
Last Updated
November 2, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT02232932
Brief Title
Liver Resection Versus Radio-chemotherapy-Transplantation for Hilar Cholangiocarcinoma
Acronym
TRANSPHIL
Official Title
Randomized Prospective Multicentric Study: Radio-chemotherapy and Liver Transplantation Versus Liver Resection to Treat Respectable Hilar Cholangiocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 2014 (undefined)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholangiocarcinoma
Keywords
Hilar cholangiocarcinoma, Liver transplantation, Radiochemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAPECITABINE-Radiotherapy -Liver Transplantation
Arm Type
Experimental
Arm Description
Neoadjuvant Radio-Chemotherapy (RC) and Liver Transplantation (LT)
Arm Title
RESECTION
Arm Type
Active Comparator
Arm Description
Liver resection
Intervention Type
Procedure
Intervention Name(s)
CAPECITABINE-Radiotherapy -Liver Transplantation
Other Intervention Name(s)
Neoadjuvant Radio-Chemotherapy and Liver Transplantation
Intervention Description
CAPECITABINE (800 mg/m2 twice a day during 5 weeks) + External Radiotherapy (50 grays during 5 weeks) then Liver transplantation
Intervention Type
Procedure
Intervention Name(s)
RESECTION
Other Intervention Name(s)
Liver Resection
Intervention Description
Intent-to-treat R0 liver resection
Primary Outcome Measure Information:
Title
Overall survival
Description
To demonstrate the superiority, in terms of 5-year survival, of liver transplantation (TH) preceded by neoadjuvant chemoradiotherapy on the radical resection of Klatskin tumors considered resectable
Time Frame
At 5 years
Secondary Outcome Measure Information:
Title
Recurrence free survival
Description
3-year recurrence-free survival assessed by CT and markers
Time Frame
At 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
68 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric VIBERT, MD
Organizational Affiliation
AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire, Villejuif, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire
City
Villejuif
ZIP/Postal Code
94
Country
France

12. IPD Sharing Statement

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Liver Resection Versus Radio-chemotherapy-Transplantation for Hilar Cholangiocarcinoma

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