Liver Transplantation for Early Intrahepatic Cholangiocarcinoma

NCT ID: NCT02878473

Last Updated: 2024-12-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-05
• Study Completion Date: 2024-12-06

Brief Summary

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.

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.

Conditions

Intrahepatic Cholangiocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Liver transplantation

The intervention will consist of liver transplantation

Group Type: EXPERIMENTAL

Deceased donor Liver Transplantation

Intervention Type: PROCEDURE

Deceased donor orthotopic liver transplantation

Interventions

Deceased donor Liver Transplantation

Deceased donor orthotopic liver transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gonzalo Sapisochin, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Jordi Bruix, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Barcelona

Locations

University Health Network

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 27481548 (View on PubMed)

Achurra P, Fernandes E, O'Kane G, Grant R, Cattral M, Sapisochin G. Liver transplantation for intrahepatic cholangiocarcinoma: who, when and how. Curr Opin Organ Transplant. 2024 Apr 1;29(2):161-171. doi: 10.1097/MOT.0000000000001136. Epub 2024 Jan 23.

Reference Type: DERIVED

PMID: 38258823 (View on PubMed)

Other Identifiers

17-5306

Identifier Type: -

Identifier Source: org_study_id