LIver Transplantation for Non-Resectable Intrahepatic CholAngiocarcinoma (LIRICA)

Azienda Sanitaria Ospedaliera10 enrolled

Overview

LIRICA is a prospective non-randomized study aimed at exploring the outcome of liver transplantation in selected patients with unresectable iCCA after a downstaging/disease control protocol 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-MR, especially in relation to lymph node locations, by correlating the results with histological examination after iliac lymphadenectomy.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Intrahepatic 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: * Histologically confirmed diagnosis of iCCA * First diagnosis of iCCA * Recurrence after R0 hepatic resection, N0, M0 without macrovascular invasion * Disease considered unsuitable for hepatic resection based on tumor location and extent or underlying liver dysfunction * Absence of major vascular invasion, extrahepatic disease, or involvement of regional lymph nodes detected on radiological study * No evidence of extrahepatic metastatic disease after chest-abdomen-pelvis CT and PET-MR (or PET-CT) * At least six months have passed since the first diagnosis of iCCA (or recurrence) to the date of inclusion on the liver transplant waiting list * The patient has received at least six months of SOC chemotherapy, achieving disease stability or partial response (according to RECIST version 1.1) at the time of listing for transplantation * Hematochemical evaluation: Hb ≥ 9 g/dL, Leukocytes ≥ 3.0 X 109/L, Neutrophils ≥ 1.5 X 109/L, Platelets ≥ 100,000/mm3 (≥ 10 X 109/L), Total Bilirubin ≤ 3 mg/dL (≤ 51 umol/L), AST or ALT ≤ 5 times the upper limit of normal, Serum Creatinine and Urea \< 1.5 times the upper limit of normal * ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1 * Patient's BMI ≥ 18 and ≤ 30 kg/m2 * Signed informed consent, and expected patient cooperation for treatment and follow-up, must be obtained and documented according to good clinical practice and national/local regulations Exclusion Criteria: * Tumor involving nearby extrahepatic structures (including involvement of major hepatic vessels) by direct invasion (T4 per AJCC 8th edition) * Tumor penetrating the visceral peritoneum (T3 per AJCC 8th edition) * Previous extrahepatic metastatic disease * Prior neoplasms, except those treated curatively for more than 5 years without recurrence * Known history of human immunodeficiency virus (HIV) infection * Known history of solid organ or bone marrow transplantation * Substance abuse and medical, psychological, or social conditions that may interfere with the patient's participation in the study or with the evaluation of study outcomes * Pregnant or breastfeeding women * Medical-surgical contraindications for liver transplantation * Any reason for which, in the investigator's judgment, the patient should not participate in the study

Outcomes

Primary Outcomes

Overall Survival

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

Time frame: 3 and 5 years

Secondary Outcomes

OS comparison with chemotherapy alone

Comparison of 3-year survival between patients enrolled in the LIRICA 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

Disease-Free Survival (DFS)

Survival from time of transplantation to time of death or first evidence of recurrence fo 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

PFS comparison with chemotherapy alone

Comparison of 3-year Progression-Free Survival (PFS) between the per-protocol population of patients enrolled in the LIRICA study and the PFS of the population from the Veneto Oncological Institute (IOV) database

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 and

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_RM staging (number, size, location)

Asses if suspicious lymph nodes described at the preoperative PET-RM confirm to be pathological at the histological evaluation after lymphadenectomy of the hepatic hilum and exploratory laparotomy. Lymph nodes will we evaluated by number, size and location

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 QLG 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 Intrahepatic CholAngiocarcinoma (LIRICA)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts