The Intention-to-treat Effect of Bridge Therapies in the Setting of Milan-in Patients

Liver Cancer Clinical Trial

Official title:

The Intention-to-treat Effect of Bridging Therapies in the Setting of Milan-in Patients Waiting for Liver Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03723304
• Other study ID #: #0002
• Status: Completed
• Start date: March 1, 2018
• Est. completion date: October 15, 2018

Study information

• Verified date: October 2018
• Source: European Hepatocellular Cancer Liver Transplant Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In patients with hepatocellular cancer (HCC) meeting the Milan Criteria (MC), the usefulness of loco-regional therapies (LRT) in the context of liver transplantation (LT) is still debated. The inconsistent literature data are the result of initial selection biases among treated and untreated patients. In order to overcome these shortcomings, an inverse probability of treatment weighting (IPTW) analysis was done in a large patient cohort. After using a competing-risk analysis, the primary end-point of the study aims at identifying the risk factors of HCC-specific LT failure, defined as pre-LT tumour-related drop-out or post-LT recurrence.

Description:

Liver transplantation (LT) is the best curative treatment of hepatocellular cancer (HCC) developed in an underlying liver disease. LT is considered as an oncologic successful procedure when a long-term post-transplant tumour-free survival is obtained. Conversely, a failure is equal to pre-transplant drop-out, post-transplant tumour recurrence or death. Due to the allograft scarcity, a HCC patient waiting for a LT is most often treated using neo-adjuvant loco-regional therapies (LRT) in order to minimise the risk of drop-out. When the tumour burden meets the Milan Criteria (MC) at moment of diagnosis, such an approach is called "bridging towards LT".

Two recent international guidelines underlined the importance of the bridging strategy, due to its potential to reduce the risk of pre-LT drop-out and post-LT recurrence. This is especially valid in the case in which a partial/complete tumour response is achieved before LT. Unfortunately, the quality of the evidence obtained from the currently available literature is low due to the lack of randomized controlled trials (RCT). Actually, it is inconceivable to realize RCT in this setting because of logistical and, even more, ethical reasons. Consequently, the majority of reported studies just compare post-LT outcome of treated and untreated patients, failing thereby to analyse the clinical course from an intention-to-treat (ITT) point of view.

Even when looking at studies including the waiting list period, one should keep in mind that substantial differences may exist among initially bridged vs untreated HCC patients regarding tumour burden. In order to overcome these limits, a retrospective analysis of a large European population of MC-IN HCC patients listed for LT was done. After "balancing" this cohort with an inverse probability of treatment weighting (IPTW), we investigated the risk factors for tumour-specific LT failure, especially focusing at the role of LRT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1083
• Est. completion date: October 15, 2018
• Est. primary completion date: October 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• adults (=18-year old) listed for liver transplant with a morphologic and/or histologic confirmed hepatocellular cancer

Exclusion Criteria:

• Milan Criteria-out status at first referral

• transplantation or de-listing before January 1, 2001

• other means of loco-regional treatments such as partial hepatectomy, trans-arterial radio-embolization or external radiotherapy

• misdiagnosed mixed hepatocellular-cholangiocellular cancer or cholangiocellular cancer

Related Conditions & MeSH terms

• Liver Cancer
• Liver Neoplasms
• Transplant; Failure, Liver

Intervention

Procedure:
• Bridging followed by transplant
Trans-arterial chemoembolization or percutaneous alcohol injection or radio-frequency ablation during the waiting time followed by liver transplant
• Direct liver transplant
Direct liver transplant (no neoadjuvant approaches during the waiting time period)

Locations

Country	Name	City	State
Belgium	UCL	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
European Hepatocellular Cancer Liver Transplant Group

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumour-specific liver transplant failure rate	Any case of tumor-related drop-out during the waiting list period or post-transplant recurrence	up to 5 years from first referral