Liver CancerNCT03723304
The Intention-to-treat Effect of Bridge Therapies in the Setting of Milan-in Patients
An observational study of Liver Cancer and Transplant; Failure, Liver, run by European Hepatocellular Cancer Liver Transplant Group at 1 site in Belgium.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cancer, Transplant; Failure, Liver
- What is being tested?
- Bridging followed by transplant and Direct liver transplant
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 1,083 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Mar 2018to 15 Oct 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with radiological/post-bioptic diagnosis of hepatocellular cancer listed for liver transplantation receiving or not receiving any neo-adjuvant treatment before transplant/drop-out
Who may be able to join
- adults (≥18-year old) listed for liver transplant with a morphologic and/or histologic confirmed hepatocellular cancer
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Intention-to-treat Effect of Bridging Therapies in the Setting of Milan-in Patients Waiting for Liver Transplantation
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.
Read the detailed 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.
- Conditions
- Liver Cancer, Transplant; Failure, Liver
- Being tested
- Bridging followed by transplant, Direct liver transplant
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bridging followed by transplantProcedure or surgery
Trans-arterial chemoembolization or percutaneous alcohol injection or radio-frequency ablation during the waiting time followed by liver transplant
Direct liver transplantProcedure or surgery
Direct liver transplant (no neoadjuvant approaches during the waiting time period)
| Study group | Role | What they receive |
|---|---|---|
| Direct liver transplant | All the cases listed for liver transplantation and then transplanted/dropped-out without undergoing any neo-adjuvant loco-regional treatment Receives: Procedure: Direct liver transplant | |
| Bridging followed by transplant | All the cases listed for liver transplantation and then transplanted/dropped-out after undergoing at least one neo-adjuvant loco-regional treatment Receives: Procedure: Bridging followed by transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumour-specific liver transplant failure rate
Any case of tumor-related drop-out during the waiting list period or post-transplant recurrence
Measured: up to 5 years from first referral
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2018
- Study start1 Mar 2018
- Primary completion15 Oct 2018
- Study completion15 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,083 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Hepatocellular Cancer Liver Transplant Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Quirino Lai, MD PhD, Principal investigator, UCL Brussels
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03723304
- Sponsor's protocol ID
- #0002
- Status last verified
- Oct 2018
- First submitted
- 25 Oct 2018
- Last updated
- 29 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lai Q, Vitale A, Iesari S, Finkenstedt A, Mennini G, Onali S, Hoppe-Lotichius M, Manzia TM, Nicolini D, Avolio AW, Mrzljak A, Kocman B, Agnes S, Vivarelli M, Tisone G, Otto G, Tsochatzis E, Rossi M, Viveiros A, Ciccarelli O, Cillo U, Lerut J; European Hepatocellular Cancer Liver Transplant Study Group. The Intention-to-Treat Effect of Bridging Treatments in the Setting of Milan Criteria-In Patients Waiting for Liver Transplantation. Liver Transpl. 2019 Jul;25(7):1023-1033. doi: 10.1002/lt.25492.
PubMed 31087772
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Intention-to-treat Effect of Bridging Therapies in the Setting of Milan-in Patients Waiting for Liver Transplantation
- ClinicalTrials.gov ID
- NCT03723304
- Acronym / sponsor ID
- #0002
- Conditions
- Liver Cancer, Transplant; Failure, Liver
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,083 participants (actual)
- Lead sponsor
- European Hepatocellular Cancer Liver Transplant GroupUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 15 Oct 2018 (actual)
- Study completion
- 15 Oct 2018 (actual)
- First posted
- 29 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Direct liver transplant | – | Procedure: Direct liver transplantAll the cases listed for liver transplantation and then transplanted/dropped-out without undergoing any neo-adjuvant loco-regional treatment |
| Bridging followed by transplant | – | Procedure: Bridging followed by transplantAll the cases listed for liver transplantation and then transplanted/dropped-out after undergoing at least one neo-adjuvant loco-regional treatment |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with radiological/post-bioptic diagnosis of hepatocellular cancer listed for liver transplantation receiving or not receiving any neo-adjuvant treatment before transplant/drop-out
Key inclusion criteria (1 listed)
- adults (≥18-year old) listed for liver transplant with a morphologic and/or histologic confirmed hepatocellular cancer
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bridging followed by transplantTrans-arterial chemoembolization or percutaneous alcohol injection or radio-frequency ablation during the waiting time followed by liver transplant | Procedure or surgery | Bridging followed by transplant |
| Direct liver transplantDirect liver transplant (no neoadjuvant approaches during the waiting time period) | Procedure or surgery | Direct liver transplant |
Primary outcome
Tumour-specific liver transplant failure rate
Time frame: up to 5 years from first referral
Any case of tumor-related drop-out during the waiting list period or post-transplant recurrence
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2018.
- Derived from this study: PubMed 31087772Lai Q, Vitale A, Iesari S, Finkenstedt A, Mennini G, Onali S, Hoppe-Lotichius M, Manzia TM, Nicolini D, Avolio AW, Mrzljak A, Kocman B, Agnes S, Vivarelli M, Tisone G, Otto G, Tsochatzis E, Rossi M, Viveiros A, Ciccarelli O, Cillo U, Lerut J; European Hepatocellular Cancer Liver Transplant Study Group. The Intention-to-Treat Effect of Bridging Treatments in the Setting of Milan Criteria-In Patients Waiting for Liver Transplantation. Liver Transpl. 2019 Jul;25(7):1023-1033. doi: 10.1002/lt.25492.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Quirino Lai, MD PhD principal investigator
UCL Brussels
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Cancer and Transplant; Failure, Liver, run by European Hepatocellular Cancer Liver Transplant Group at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumour-specific liver transplant failure rate (time frame: up to 5 years from first referral). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03723304, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2018.