Liver Transplantation for Non-Resectable Intrahepatic Cholangiocarcinoma: a Prospective Exploratory Trial (TESLA Trial)

Study Overview
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Brief Summary
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The study will investigate whether liver transplantation provides increased survival, low side effects and good quality of life in patients with bile duct cancer where the tumor cannot be removed by normal surgery. Analyzes of blood and tissue samples from the tumor will be investigated to see if the analyzes can indicate who may have recurrence of the disease after liver transplantation. Furthermore, the effect of chemotherapy on normal liver and tumor tissues in the liver that are removed during transplantation will be investigated..

Official Title
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Liver Transplantation for Non-Resectable Intrahepatic Cholangiocarcinoma: a Prospective Exploratory Trial (TESLA Trial)

Conditions
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Intrahepatic Cholangiocarcinoma

Intervention / Treatment
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* Procedure: Liver Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified diagnosis of Intrahepatic Cholangiocarcinoma (iCCA) First time iCCA or liver only recurrence after previous liver resection for iCCA Disease deemed not eligible for liver resection based on tumor location or underlying liver dysfunction No vascular invasion, extrahepatic disease, or lymph node involvement detected on imaging No signs of extrahepatic metastatic disease according to positron emission computed tomography (PET-CT) scan Patient must be accepted for transplantation before progressive disease on chemotherapy. Twelve months or more time span from the diagnosis of iCCA and date of being listed for liver transplantation No signs of extrahepatic metastatic disease according to CT or magnetic resonance (MR) scan within 4 weeks prior to the faculty meeting at the transplant unit At least 18 years of age Good performance status, Eastern Cooperative Oncology Group (ECOG) 0 or 1 Signed informed consent and expected cooperation of the patients for the treatment and follow up Received at least 6 months of chemotherapy or locoregional therapy Exclusion Criteria: Major vascular involvement of the tumor Perforation of the visceral peritoneum Weight loss >15% the last 6 months Patient BMI > 30 Other malignancies, except curatively treated more than 5 years ago without relapse Known history of human immunodeficiency virus (HIV) infection Prior history of solid organ or bone marrow transplantation Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results Known hypersensitivity to rapamycin Prior extrahepatic metastatic disease Women who are pregnant or breast feeding Any reason why, in the opinion of the investigator, the patient should not participate

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liver Transplant<br>The patients will be transplanted according to standard procedures by the institutional protocol. The transplantation procedure is initiated by an exploratory laparotomy with clinical assessment and frozen section of the lymphnodes in the hepatoduodenal ligament and along the common hepatic artery/coeliac axis. Evidence of disease dissemination to these regional lymph nodes will be an absolute contraindication to transplantation. | Procedure: Liver Transplant<br>* Liver Transplant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS as assessed by quality of life questionnaire (QLQ-C30) patient reported outcome | From screening and until 36 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival from time of relapse | OS as assessed by QLQ-C30 patient reported outcome | From time of relapse and until 36 months after inclusion | 
| Disease free survival | CT-scan/MRI scan according to RECISTcriteria | After liver transplantation and up 10 years after liver transplantation | 
| Start of new treatment/Change of strategy | Time to start of new treatment | Immediately after liver transplatation to start of new treatment | 
| Time to decrease in physical function and global health score | Quality of life measured by EORTC QLQ-C30), | Up to 10 years after liver transplantation | 
| Liver transplant Complication | Number of Clavien-Dindo grad 3-5 complications | Up to 90 days after liver transplantation | 
| Number of Participants Developing other Malignancies | Diagnosis of other malignancies | Up to 10 years after liver transplantation | 
| Survival in relation to biological markers | CEA, CA 19-9 and Germline DNA analyses | After Liver Transplant until 10 years after liver transplantation |