Clinical trial NCT06539377: Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma
Official title: Living Donor Liver Transplantation for Neoadjuvant Treated, Unresectable Intrahepatic Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Living Donor Liver Transplantation
Liver Transplantation
Neoadjuvant Therapy
Keywords: intrahepatic cholangiocarcinoma
living donor liver transplantation
neoadjuvant therapy
SIRT
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
First posted: 2024-08-06
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Curative treatment of unresectable intrahepatic cholangiocarcinoma via living donor donation and one- or two-staged hepatectomy
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Five year overall survival
timeFrame: Five years
Secondary outcomes:
measure: Recurrence-free survival
timeFrame: Five years
measure: Donor and Recipient morbidity
timeFrame: Five years
Other outcomes:
Locations:
Study officials:
affiliation: Jena University Hospital
name: Utz Settmacher, Prof
role: STUDY_DIRECTOR
affiliation: Jena University Hospital
name: Falk Rauchfuss, Prof
role: STUDY_DIRECTOR
affiliation: Jena University Hospital
name: Laura Schwenk, MD
role: STUDY_DIRECTOR
References:
citation: Goldaracena N, Gorgen A, Sapisochin G. Current status of liver transplantation for cholangiocarcinoma. Liver Transpl. 2018 Feb;24(2):294-303. doi: 10.1002/lt.24955.
citation: Ziogas IA, Giannis D, Economopoulos KP, Hayat MH, Montenovo MI, Matsuoka LK, Alexopoulos SP. Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Meta-analysis and Meta-regression of Survival Rates. Transplantation. 2021 Oct 1;105(10):2263-2271. doi: 10.1097/TP.0000000000003539.
citation: Chan KM, Tsai CY, Yeh CN, Yeh TS, Lee WC, Jan YY, Chen MF. Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence. BMC Gastroenterol. 2018 Dec 4;18(1):180. doi: 10.1186/s12876-018-0912-x.
citation: Lunsford KE, Javle M, Heyne K, Shroff RT, Abdel-Wahab R, Gupta N, Mobley CM, Saharia A, Victor DW, Nguyen DT, Graviss EA, Kaseb AO, McFadden RS, Aloia TA, Conrad C, Li XC, Monsour HP, Gaber AO, Vauthey JN, Ghobrial RM; Methodist-MD Anderson Joint Cholangiocarcinoma Collaborative Committee (MMAJCCC). Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. Lancet Gastroenterol Hepatol. 2018 May;3(5):337-348. doi: 10.1016/S2468-1253(18)30045-1. Epub 2018 Mar 13.
citation: McMillan RR, Javle M, Kodali S, Saharia A, Mobley C, Heyne K, Hobeika MJ, Lunsford KE, Victor DW 3rd, Shetty A, McFadden RS, Abdelrahim M, Kaseb A, Divatia M, Yu N, Nolte Fong J, Moore LW, Nguyen DT, Graviss EA, Gaber AO, Vauthey JN, Ghobrial RM. Survival following liver transplantation for locally advanced, unresectable intrahepatic cholangiocarcinoma. Am J Transplant. 2022 Mar;22(3):823-832. doi: 10.1111/ajt.16906. Epub 2021 Dec 27.