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

Azienda Sanitaria Ospedaliera50 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Perihilar Cholangiocarcinoma

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Overall Survival (OS)

Survival from time of transplantation to time of death or last follow up

Time frame: 3 and 5 years

Secondary Outcomes

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)

Time frame: 3 years

Progression-Free Survival (PFS)

Survival from time of transplantation to time of death or first evidence of progression of disease

Time frame: 3 and 5 years

Overall survival from the time of recurrence

Survival from time of recurrence to time of death or last follow up

Time frame: 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)

Time frame: 3 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)

Time frame: 5 years

Morbidity

Morbidity at 90 days (according to Clavien-Dindo and Comprehensive Complication Index, CCI)

Time frame: 90 days

Cancer-related mortality

Risk of mortality with sole relation to death by tumor progression

Time frame: 3 and 5 years

Drop out

Percentage of patients who do not complete the procedure (drop-out) stratified by cause

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 5 years

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts