Liver Transplantation for Early Intrahepatic Cholangiocarcinoma

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Intrahepatic Cholangiocarcinoma

Intervention / Treatment
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* Procedure: Deceased donor Liver Transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liver transplantation<br>The intervention will consist of liver transplantation | Procedure: Deceased donor Liver Transplantation<br>* Deceased donor orthotopic liver transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |