LIver Transplantation for Non-Resectable Intrahepatic CholAngiocarcinoma (LIRICA) (LIRICA)

January 23, 2024 updated by: Enrico Gringeri, Azienda Sanitaria Ospedaliera
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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Italy
      • Padova, Italy, 35128
        • Recruiting
        • Azienda Ospedale Universita Di Padova
        • Contact:
        • 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:
          • Mario D Rizzato, Dr.
        • Sub-Investigator:
          • Martina Gambato, Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Study population

Candidates will be evaluated by theMultidisciplinary Group after routine radiological studies (CT, MRI, PET-MR/CT).

Patients will receive 6 months of standard of care chemotherapy and undergo PET-MR with FDG to exclude the presence of extrahepatic disease.

Following completion of therapy, patients will undergo radiological restaging. If the disease is resectable, the patient will be considered for curative-intent surgical resection; if not, the patients will be evaluated by the Center's Multidisciplinary Transplantation Group.

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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 3 and 5 years
Survival from time of transplantation to time of death or last follow up
3 and 5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
OS comparison with chemotherapy alone
Time Frame: 3 years
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)
3 years
Disease-Free Survival (DFS)
Time Frame: 3 and 5 years
Survival from time of transplantation to time of death or first evidence of recurrence fo disease
3 and 5 years
Overall survival from the time of recurrence
Time Frame: 5 years
Survival from time of recurrence to time of death or last follow up
5 years
PFS comparison with chemotherapy alone
Time Frame: 3 years
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
3 years
Biological markers
Time Frame: 5 years
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
Time Frame: 90 days
Morbidity at 90 days (according to Clavien-Dindo and Comprehensive Complication Index, CCI)
90 days
Cancer-related mortality
Time Frame: 3 and 5 years
Risk of mortality with sole relation to death by tumor progression and
3 and 5 years
Drop out
Time Frame: 5 years
Percentage of patients who do not complete the procedure (drop-out) stratified by cause
5 years
Concordance of surgical and PET_RM staging (number, size, location)
Time Frame: Perioperative
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
Perioperative
Quality of life assessed using EORTC QLQ-C30
Time Frame: 5 years
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)
5 years
Quality of life assessed using FACT-Hep questionnaire
Time Frame: 5 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Azienda Sanitaria Ospedaliera

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Istituto Oncologico Veneto IRCCS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Enrico Gringeri, Prof., Azienda Ospedale Universita Di Padova

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 15, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2033

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 18, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 21, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 24, 2023

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 24, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AOP 3006
  • LIRICA (Other Identifier: University of Padova)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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