LIver TrAnspLantation for Non-resectable Peri-HIlar cholangioCArcinoma (LITALHICA) (LITALHICA)

LITALHICA is a prospective non-randomized study aimed at exploring the outcome of liver transplantation in selected patients with unresectable perihilar cholangiocarcinoma (pCCA) after treatment with standard of care chemotherapy, in terms of overall survival and quality of life. Additionally, the study aims to identify pre-transplant biological markers and clinical factors that can stratify patients with the best post-transplant prognosis. Finally, the study aims to investigate the role of preoperative PET-MRI, especially in relation to lymph node locations, by correlating the results with histological examination after hilar lymphadenectomy.

Study Overview

• Status: Recruiting
• Conditions: Perihilar Cholangiocarcinoma
• Intervention / Treatment: Procedure: Liver transplantation

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Enrico Gringeri, Prof.; Phone Number: +39 0498218547; Email: enrico.gringeri@unipd.it

Study Locations

• Italy
  • PADOVA
    • Padova, PADOVA, Italy, 35128
      • Recruiting
      • Azienda Ospedale Università di Padova
      • Contact: Enrico Gringeri, Prof.; Phone Number: +39 0498218547; Email: enrico.gringeri@unipd.it
      • Principal Investigator: Enrico Gringeri, Prof.
      • Sub-Investigator: Umberto Cillo, Prof.
      • Sub-Investigator: Domenico Bassi, Dr.
      • Sub-Investigator: Alessandra Bertacco, Dr.
      • Sub-Investigator: Riccardo Boetto, Dr.
      • Sub-Investigator: Francesco Enrico D'Amico, Prof
      • Sub-Investigator: Annalisa Dolcet, Dr.
      • Sub-Investigator: Jacopo Lanari, Dr.
      • Sub-Investigator: Alessandro Vitale, Prof.
      • Sub-Investigator: Alessandro Furlanetto, Dr.
      • Sub-Investigator: Sara Lonardi, Dr.
      • Sub-Investigator: Francesca Bergamo, Dr.
      • Sub-Investigator: Caterina Solda', Dr.
      • Sub-Investigator: Martina Gambato, Dr.
      • Sub-Investigator: Mario Domenico Rizzato, Dr.
      • Sub-Investigator: Francesco Ferrara, Dr.
      • Sub-Investigator: Marco Krengli, Prof.
      • Sub-Investigator: Sara Galuppo, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of pCCA (transcatheter biopsy or brush cytology, CA 19-9 > 100 mg/mL and/or a mass on cross-sectional imaging with a malignant appearing stricture on cholangiography, or biliary ploidy with a malignant appearing stricture on cholangiography)
• Unresectable tumor above cystic duct (pancreatoduodenectomy for microscopic involvement of CBD) or resectable pCCA arising in PSC
• Absence of major vascular invasion, extrahepatic disease, or involvement of regional lymph nodes
• No extrahepatic metastatic disease
• Radial tumor diameter ≤3 cm
• At least six months between first diagnosis of pCCA and date of inclusion
• At least six months of SOC chemotherapy, achieving disease stability or partial response

Exclusion Criteria:

• Uncontrollable infection
• Prior radiotherapy or chemotherapy
• Prior biliary surgical resection or attempted surgical resection
• Diameter of tumor >3cm
• Presence of intra-hepatic metastases or iCCA
• Present or past evidence of extrahepatic metastatic disease
• Transperitoneal biopsy (including percutaneous ecography-guided FNA)
• Prior neoplasms, except those treated curatively for more than 5 years without recurrence
• Substance abuse and medical, psychological, or social conditions that may interfere with the patient's participation in the study
• Pregnant or breastfeeding women
• Medical-surgical contraindications for liver transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study population; Candidates will be evaluated by a National Multidisciplinary Group after routine radiological studies (CT, MRI, PET-MRI/CT). Patients will receive 6 months of standard of care chemotherapy and undergo PET-MRI with FDG to exclude the presence of extrahepatic disease. Following completion of therapy, patients will undergo radiological restaging: those who demonstrate stable disease at this stage are considered eligible for definitive listing for LT. Patients will continue chemotherapy until a compatible liver becomes available. If there are no further contraindications, exploratory laparotomy and surgical nodal staging of the tumor will be performed at the time of transplantation. If there are no signs of extrahepatic disease, transplantation will be conducted according to institutional protocols.

Procedure: Liver transplantation; Patients will undergo liver transplantation according to the standard procedures of the institutional Center's protocol (cadaveric or living donor transplantation, whole or partial liver). Liver transplantation is preceded by an exploratory laparotomy with clinical evaluation and frozen section examination of lymph nodes in the hepatoduodenal ligament and along the common hepatic artery/celiac axis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Survival from time of transplantation to time of death or last follow up	3 and 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival from the time of recurrence	Survival from time of recurrence to time of death or last follow up	5 years
Biological markers	Correlation of overall survival and recurrence with tissue and circulating biological markers (immunohistochemistry, proteomics, circulating tumor cells, circulating tumor DNA, new molecular markers)	5 years
Morbidity	Morbidity at 90 days (according to Clavien-Dindo and Comprehensive Complication Index, CCI)	90 days
Drop out	Percentage of patients who do not complete the procedure (drop-out) stratified by cause	5 years
Quality of life assessed using FACT-Hep questionnaire	Quality of life assessed using FACT-Hep questionnaire (Functional Assessment of Cancer Therapy - Hepatobiliary) questionnaire about quality of life in the last 7 days (scale 0-4, 0 being the lowest and 4 the highest)	5 years
Overall survival comparison with chemotherapy alone	Comparison of 3-year survival between patients enrolled in the LITALHICA study and survival of a population balanced for prognostic factors and disease characteristics from the database of the Veneto Oncological Institute (IOV)	3 years
Progression-Free Survival (PFS)	Survival from time of transplantation to time of death or first evidence of progression of disease	3 and 5 years
Progression-free survival comparison with chemotherapy alone	Comparison of 3-year progression-free survival between patients enrolled in the LITALHICA study and progression-free survival of a population balanced for prognostic factors and disease characteristics from the database of the Veneto Oncological Institute (IOV)	3 years
Cancer-related mortality	Risk of mortality with sole relation to death by tumor progression	3 and 5 years
Concordance of surgical and PET/MRI staging	Asses if lymph nodes described as suspicious at the preoperative PET-MRI confirm to be pathological at the histological evaluation after lymphadenectomy of the hepatic hilum and exploratory laparotomy	Perioperative
Quality of life assessed using EORTC QLQ-C30	Quality of life assessed using EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer QLQ Core Questionnaire) 30 items questionnaire (scale 1-4 or 1-7, 1 being the lowest and 4 or 7 the highest, accordingly)	5 years

Collaborators and Investigators

• Sponsor: Azienda Sanitaria Ospedaliera
• Collaborators: Istituto Oncologico Veneto IRCCS
• Investigators: Principal Investigator: Enrico Gringeri, Prof., Azienda Ospedale Università di Padova

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2033

Study Registration Dates

• First Submitted: October 30, 2023
• First Submitted That Met QC Criteria: November 5, 2023
• First Posted (Actual): November 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Liver transplantation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Klatskin Tumor; Therapeutics; Surgical Procedures, Operative; Transplantation; Digestive System Surgical Procedures; Cell- and Tissue-Based Therapy; Biological Therapy; Tissue Transplantation; Organ Transplantation; Liver Transplantation
• Other Study ID Numbers: AOP 3007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No