- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03172559
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
Withdrawn
Conditions
Intervention / Treatment
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
Interventional
Phase
- 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
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 |
Intervention / Treatment |
---|---|
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.
|
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:
|
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
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
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.
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)
September 1, 2020
Primary Completion (ANTICIPATED)
September 1, 2026
Study Completion (ANTICIPATED)
September 1, 2029
Study Registration Dates
First Submitted
April 5, 2017
First Submitted That Met QC Criteria
May 29, 2017
First Posted (ACTUAL)
June 1, 2017
Study Record Updates
Last Update Posted (ACTUAL)
August 20, 2020
Last Update Submitted That Met QC Criteria
August 18, 2020
Last Verified
August 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID 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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