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

Perihilar Cholangiocarcinoma Clinical Trial

— LITALHICA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06125769
• Other study ID #: AOP 3007
• Status: Recruiting
• Phase: N/A
• Start date: January 15, 2024
• Est. completion date: November 1, 2033

Study information

• Verified date: January 2024
• Source: Azienda Sanitaria Ospedaliera
• Contact: Enrico Gringeri, Prof.
• Phone: +39 0498218547
• Email: enrico.gringeri[@]unipd.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: November 1, 2033
• Est. primary completion date: November 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

• 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)

• Unresectable tumor above cystic duct (pancreatoduodenectomy for microscopic involvement of CBD) or resectable pCCA arising in PSC

• Radial tumor diameter <3 cm

• At least six months have passed since the first diagnosis of pCCA to the date of inclusion on the liver transplant waiting list

• The patient has received at least six months of standard of care (SOC) chemotherapy, achieving disease stability or partial response (according to RECIST criteria version 1.1) at the time of listing for transplantation

• Absence of medical or surgical contraindication to liver transplantation

• 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:

• Diagnosis of intrahepatic cholangiocarcinoma (iCCA)

• Uncontrollable infection

• Prior radiotherapy or chemotherapy

• Prior biliary surgical resection or attempted surgical resection

• Diameter of tumor >3cm

• Presence of intra-hepatic metastases

• 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 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

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Klatskin Tumor
• Perihilar Cholangiocarcinoma

Intervention

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.

Locations

Country	Name	City	State
Italy	Azienda Ospedale Università di Padova	Padova

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Sanitaria Ospedaliera	Istituto Oncologico Veneto IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Survival from time of transplantation to time of death or last follow up	3 and 5 years
Secondary	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
Secondary	Progression-Free Survival (PFS)	Survival from time of transplantation to time of death or first evidence of progression of disease	3 and 5 years
Secondary	Overall survival from the time of recurrence	Survival from time of recurrence to time of death or last follow up	5 years
Secondary	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
Secondary	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
Secondary	Morbidity	Morbidity at 90 days (according to Clavien-Dindo and Comprehensive Complication Index, CCI)	90 days
Secondary	Cancer-related mortality	Risk of mortality with sole relation to death by tumor progression	3 and 5 years
Secondary	Drop out	Percentage of patients who do not complete the procedure (drop-out) stratified by cause	5 years
Secondary	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
Secondary	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
Secondary	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