Liver Transplantation for Early Intrahepatic Cholangiocarcinoma (LT for iCCA)

Liver Transplantation for the Treatment of Early Stages of Intrahepatic Cholangiocarcinoma in Cirrhotics

Diagnosis of intrahepatic cholangiocarcinoma (iCCA) is increasingly common in patients with liver cirrhosis, but these patients are denied liver transplantation (LT) by most centres due to historically poor results. Two retrospective evaluations have shown a 5 year survival ~65% in selected patients with an iCCA diagnosis at the pathology of the explanted liver. This suggests that LT can be a curative treatment if applied selectively. This study will evaluate the effectiveness of LT as a treatment for very early iCCA diagnosed in cirrhotic patients who meet the strict selection criteria. Patients with advanced cirrhosis (not candidates for resection) currently have no other curative treatment options. Participants will be allowed bridging therapies prior to receiving transplant. Participants will be followed for 5 years from the time of transplant with patient survival and disease recurrence as outcome measures.

Study Overview

• Status: Terminated
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Procedure: Deceased donor Liver Transplantation

Detailed Description

Diagnosis of intrahepatic cholangiocarcinoma (iCCA) is increasingly common in patients with liver cirrhosis. iCCA is not an indication for Liver transplantation (LT) at most transplant centres given the historically poor rates of survival and high rates of disease recurrence. A recent retrospective study shows that patients found to have very early iCCA on explant after undergoing LT for another indication, had a 5 year survival of 65% and recurrence rate of 13%.This suggests that LT can be a curative treatment if applied selectively and that it is time to reevaluate LT as a treatment option for those with very early iCCA. This study will evaluate the effectiveness of LT as a treatment for very early iCCA diagnosed in cirrhotic patients. Diagnosis of iCCA will be based upon biopsy results of a new tumor which does not present radiologically as an HCC. Patients fulfilling the strict study selection criteria will undergo a full transplant assessment and must be deemed otherwise "suitable" for liver transplant as per their centre's criteria. Patients will be treated with bridging therapies while they are on the transplant waiting list according to each center's policy. Patients with disease progression (tumor >3cm or development of extrahepatic disease) at any time prior to transplantation will be excluded. Participants will be followed for 5 years from the time of transplant with patient survival and disease recurrence as outcome measures.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group: 0 or 1 at all times prior to Liver Transplantation
• Absence of cancer-related symptoms
• Liver cirrhosis (any etiology)
• Patient not eligible for liver resection due to poor liver function/portal hypertension
• Biopsy proven "very early" intrahepatic cholangiocarcinoma (iCCA)
• Willing and able to provide written informed consent.
• Negative serum pregnancy test for women of childbearing potential
• Biopsy proven "very early" (single ≤2 cm) iCCa
• No vascular or biliary involvement seen in preoperative imaging
• No extra-hepatic disease seen in preoperative imaging
• Carbohydrate Antigen (CA) 19.9 values are ≤100 ng/mL

Exclusion Criteria:

• Previous or concurrent cancer (with some exceptions)
• Patients that have had previous liver resection for iCCA and the current tumor is a recurrence.
• Progression of the tumor in size >3 cm or development of extrahepatic disease.
• Large vessel invasion, defined radiologically.
• Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min
• Pulmonary insufficiency
• History of cardiac disease:
• Uncontrolled infection(s)
• Known history of human immunodeficiency virus (HIV) infection.
• History of solid organ transplantation
• Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
• Pregnant or breast-feeding patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liver transplantation; The intervention will consist of liver transplantation	Procedure: Deceased donor Liver Transplantation; Deceased donor orthotopic liver transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
5 year patient survival	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease recurrence after liver transplantation	5-years cumulative risk of recurrence after LT.	5 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Jordi Bruix, MD, Hospital Clinic of Barcelona; Principal Investigator: Gonzalo Sapisochin, MD, University Health Network, Toronto

Publications and helpful links

General Publications

• Sapisochin G, Facciuto M, Rubbia-Brandt L, Marti J, Mehta N, Yao FY, Vibert E, Cherqui D, Grant DR, Hernandez-Alejandro R, Dale CH, Cucchetti A, Pinna A, Hwang S, Lee SG, Agopian VG, Busuttil RW, Rizvi S, Heimbach JK, Montenovo M, Reyes J, Cesaretti M, Soubrane O, Reichman T, Seal J, Kim PT, Klintmalm G, Sposito C, Mazzaferro V, Dutkowski P, Clavien PA, Toso C, Majno P, Kneteman N, Saunders C, Bruix J; iCCA International Consortium. Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment. Hepatology. 2016 Oct;64(4):1178-88. doi: 10.1002/hep.28744. Epub 2016 Aug 24.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2018
• Primary Completion (Actual): December 6, 2024
• Study Completion (Actual): December 6, 2024

Study Registration Dates

• First Submitted: August 17, 2016
• First Submitted That Met QC Criteria: August 22, 2016
• First Posted (Estimated): August 25, 2016

Study Record Updates

• Last Update Posted (Actual): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma
• Other Study ID Numbers: 17-5306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No