Radiotherapy Versus no Intervention in Adult Patients With Hepatocellular Carcinoma Not Eligible for Transarterial Chemoembolization or Ablation Prior to Liver Transplant (RADBRI) (RADBRI)

August 18, 2020 updated by: University Health Network, Toronto

A Multi-Center Randomized Controlled Trial Comparing Stereotactic Body Radiotherapy as a "Bridge" Prior to Liver Transplant for Hepatocellular Carcinoma Versus no Intervention in Patients Not Eligible to Transarterial Chemoembolization or Ablation

Liver transplantation (LT) represents the best treatment for patients with selected, early stage hepatocellular carcinoma (HCC). Due to the gap between the number of patients on the waiting list and the available donors, patients with HCC wait ~1 year to be transplanted. While waiting, 25-30% of patients need to come off the transplant list due to tumor progression beyond transplant criteria (extrahepatic disease, vascular invasion or increase in tumor burden beyond enlistment criteria). To try to avoid this progression, patients are treated while waiting with "bridging therapies", mainly transarterial chemoembolization (TACE) and ablation. Around 30% of patients are not eligible for these treatments (.e.g. due to poor liver function). Stereotactic body radiotherapy (SBRT) has been shown to be an effective treatment for advanced HCC in primarily small, single institutional studies and its safety has been reported in cirrhotics. SBRT could be used in patients not eligible to TACE or ablation as a bridge to LT reducing the risk of progression in the waiting list. This study will evaluate if patients with liver cirrhosis and HCC benefit from receiving SBRT while awaiting LT. Patients will be randomized to a treatment arm where they will receive SBRT as a bridge therapy or to a no intervention arm. Outcomes prior and post to transplant will be performed to evaluate the differences between both arms: proportion of patients that do not drop-out of the list (are transplanted), liver decompensation while waiting, perioperative measures in those that are transplanted, time to transplant or drop-out, overall survival, disease-free survival in those that are transplanted in a population of about 330 patients across all sites.

Study Overview

Status

Status

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Withdrawn

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.

Detailed Description

The RADBRI trial is designed as an explanatory, multicenter, open-label, 2-arm parallel group superiority randomized trial with stratification by center and blood group, random permuted blocks (lengths of 4 or 6) and balanced allocation (1:1) conducted in 8 centers across the world. Including a population of adult patients with hepatocellular carcinoma (HCC) included in the waiting list for a liver transplant (LT) that are not eligible for transarterial chemoembolization (TACE) or ablation as a bridge to transplant but are eligible to stereotactic body radiotherapy (SBRT). Participants will be randomly assigned to either no intervention or SBRT with a 1:1 allocation as per an online, central randomization service (Sealed Envelope™) and stratified by site and by blood type (ABO type) using random permuted blocks (lengths 4 or 6). Aiming for a total sample of 332 (166 per group). Patients will be followed for 18 months until drop-out from waiting list or LT. A computed tomography (CT) or magnetic resonance imaging (MRI) and alpha-fetoprotein (AFP) level will be performed every 3 months while waiting. In those that get transplanted, follow-up will be carried out for additional 36 months (every 3 months for the first 2 years and every 6 months thereafter).

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

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

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

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18-75 years old
  • Patient has been included in the waiting list to receive a Liver Transplant (LT)
  • Radiological confirmation of Hepatocellular carcinoma (HCC) according to American Association for the Study of Liver Diseases (AASLD) guidelines
  • Tumor burden at randomization within a total tumor volume (TTV) ≤115 cm3 and serum alpha-fetoprotein (AFP) ≤400 ng/mL
  • Patient not eligible to bridging therapy with Transarterial Chemoembolization (TACE) and/or ablation.
  • Child-Pugh score ≤B9
  • Calculated Model of End Stage Liver disease (MELD) score ≤20
  • Eligible to Stereotactic body radiotherapy (SBRT): >40% of liver parenchyma can be spared from radiation and all tumors can be targeted
  • No previous treatment of the tumor
  • Absence of extra-hepatic disease or vascular invasion on imaging
  • Able and willing to provide consent

Exclusion Criteria:

  • Patient with HCC not candidate to receive a LT
  • Patient is eligible to TACE or ablation as a bridge to LT
  • Patient is not eligible to SBRT
  • Previous bridging therapies

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: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

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: Stereotactic body radiotherapy
Stereotactic body radiotherapy (SBRT) treatment will be individualized with the dose based on baseline liver function, effective liver volume irradiated and proximity to other normal tissues. The recommended dose will be 30 gray (Gy) in 5 fractions. The treatment will be administered in 5 alternative days. Patients will come every other day to the hospital to be treated and will not need to be admitted. Patients will not receive further SBRT on the treated tumor.
Radiation: Stereotactic body radiotherapy
The recommended dose will be 30 Gy in 5 fractions. The treatment will be administered in 5 alternative days and will be individualized with the dose based on baseline liver function, effective liver volume irradiated and proximity to other normal tissues.
Other Names:
  • SBRT
NO_INTERVENTION: No intervention
Follow-up will be carried out every 3 months and a computed tomography (CT) scan of the chest and abdomen or an magnetic resonance imaging (MRI), and blood work with liver function test and alpha-fetoprotein (AFP) value will be done until the patient is transplanted or drops-out of the waiting list.

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
Difference between the two treatment arms in the proportion of participants that get to be transplanted (do not drop-out from the waiting list due to tumor progression).
Time Frame: 5 years
Treatment success is defined as being transplanted. Treatment failure is defined as dropping off the waiting list for any cause (tumor progression or liver decompensation)
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
Difference between the two arms in liver decompensation while waiting
Time Frame: 5 years
Defined as an increase in the Child-Pugh score measured in each follow-up visit while the patient is in the waiting list will be compared between patients in each arm
5 years
Difference between the two arms in perioperative measures
Time Frame: 5 years
Proportion of patients with major complications measured in the first 90 days post Liver Transplant
5 years
Difference between the two arms in time to transplant or drop-out
Time Frame: 5 years
Time to event (drop-out or transplant) between both groups
5 years
Difference between the two arms in overall survival
Time Frame: 5 years
Time-to-event between both groups. This comparison will be done from the time of randomization and from the time of Liver Transplant (LT) in those that get transplanted. Causes of death after transplant will be collected and compared between groups.
5 years
Difference between the two arms in overall survival
Time Frame: 5 years
Time-to-event between both groups. This comparison will be done from the time of randomization and from the time of Liver Transplant (LT) in those that get transplanted. We will assess the effect of Stereotactic body radiotherapy (SBRT) post LT and this will be used a hypothesis generating information for future trials
5 years
Difference between the two arms in disease-free survival
Time Frame: 5 years
Time-to-event between both groups. Tumor recurrence (new Hepatocellular carcinoma after liver transplant) and patterns of recurrence
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.
University Health Network, Toronto

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 (ANTICIPATED)

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.
September 1, 2020

Primary Completion (ANTICIPATED)

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.
September 1, 2026

Study Completion (ANTICIPATED)

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.
September 1, 2029

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).
April 5, 2017

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.
May 29, 2017

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.
June 1, 2017

Study Record Updates

Last Update Posted (ACTUAL)

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.
August 20, 2020

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.
August 18, 2020

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.
August 1, 2020

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.
  • 17-5329

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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