Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma

Not Applicable

Not yet recruiting

• Conditions: Neoadjuvant Therapy; Living Donor Liver Transplantation; Liver Transplantation
• Interventions: Procedure: Living donor liver transplantation

• Registration Number: NCT06539377
• Lead Sponsor: Jena University Hospital

Brief Summary

This study is supposed to make liver transplantation available for treatment in well selected patients suffering from non-resectable intrahepatic cholangiocarcinoma. Donor organ shortage is currently the main problem for organ transplantation world-wide. Thus, the particular indication "non-resectable intrahepatic cholangiocarcinoma" is currently excluded in terms of transplantation. Given those circumstances, transplantation via living donation might be the best option. This procedure does not reduce the deceased donor organ supply because living donation is the primary treatment option in these patients (not subsidiary).

Detailed Description

Intrahepatic cholangiocarcinoma (iCCA) is classified among primary liver tumors and has demonstrated a consistently increasing incidence in recent years. Due to the poor long-term survival rates reported in older studies, liver transplantation continues to be a contraindication in the curative treatment of iCCA. The persistent shortage of organs also necessitates that each new indication for transplantation be carefully evaluated and critically scrutinized. Currently, partial resection remains the preferred treatment modality, although at diagnosis, only approximately 20% of cases are amenable to this approach. Post-partial resection, the five-year survival rate is observed to be between 20-34%. In cases of irresectability, palliative chemotherapy often remains the only option, typically associated with a poor prognosis. Numerous studies have demonstrated that long-term outcomes following liver transplantation for iCCA have evolved and improved over the years. In a meta-analysis by Ziogas et al., data from a total of 18 studies (involving 355 patients) and one registry study (385 patients) were analyzed. The pooled 1-, 3-, and 5-year survival rates were 75%, 56%, and 42%, respectively. Meanwhile, the pooled 1-, 3-, and 5-year recurrence-free survival rates were 70%, 49%, and 38%, with an overall recurrence rate of 43%. A potential reason for this marked improvement may be attributed to the introduction of neoadjuvant therapy. Studies by Hu et al. and Lunsford et al. have demonstrated that the utilization of neoadjuvant therapy is associated with significantly improved survival outcomes. The study aims to conduct a prospective, non-randomized study (LIVINCA) to further explore the effects of living-donor liver transplantation in the treatment of unresectable neoadjuvant treated (chemotherapy AND selective internal radiotherapy) intrahepatic cholangiocarcinoma.

Study Timeline

• Study First Submitted: 2024-07-30
• Status Verified: 2024-08
• Study First Submitted QC: 2024-08-01
• Last Update Submitted: 2024-08-01
• Study First Posted: 2024-08-06
• Last Update Posted: 2024-08-06
• Study Start: 2024-09-01
• Primary Completion: 2030-10-01
• Study Completion: 2031-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• non-resectable intrahepatic cholangiocarcinoma (either for localization / distribution of the carcinoma or for estimated function of the liver in case of liver fibrosis / cirrhosis)
• biopsy proven grading G1 / G2
• in case of mixed hepatocellular carcinoma / cholangiocarcinoma, the cholangiocarcinoma also must have a grading of G1 / G2
• response to chemotherapy in terms of stable or regressive disease (imaging studies, tumor marker CA19-9, any chemotherapy regime allowed, a local-ablative therapy in means of a SIRT is mandatory
• peritoneal carcinosis / extrahepatic spread ruled out in PET-CT and/or MRT/CT and, at latest, during exploration
• age ≥ 18
• blood-group compatible living donor available
• in female patients: negative pregnancy test
• written informed consent before study enrolment of donor and recipient (all other procedures are clinical routine procedures in the management of these patients)

Exclusion Criteria

• extrahepatic tumor/metastases
• G3 tumors
• progress under neoadjuvant treatment according to the RECIST-criteria
• pregnancy or breastfeeding
• patients unwilling to consent to saving and propagation of pseudonymized medical data for study reasons
• general contraindications for liver transplantation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Living donor liver transplantation	Living donor liver transplantation	The evaluation tests prior the transplantation will be performed following the standard protocol for the evaluation of a waiting list applicants prior liver transplantation. The aim of this procedure is to rule out any significant co-morbidities (e.g. cardiologic diseases, other malignancies) which would preclude liver transplantation. After successful evaluation of the recipient and waiting list registration with Eurotransplant, the AB0-compatible donor will be evaluated as well according to a center-specific protocol. For a local control of the tumor, an additional local-ablative therapy (SIRT) is mandatory.

Primary Outcome Measures

Name	Time	Method
Five year overall survival	Five years	Survival from time of transplantation to time of death or last follow up

Secondary Outcome Measures

Name	Time	Method
Recurrence-free survival	Five years	Survival from time of transplantation to time of death or first evidence of recurrence to disease
Donor and Recipient morbidity	Five years	Donor and Recipient morbidity (both according to the Clavien-Dindo classification)