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

Primary Purpose

Hepatocellular Carcinoma

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Stereotactic body radiotherapy
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Stereotactic body radiotherapy, SBRT, Radiotherapy, Bridging therapy, Transplant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    Stereotactic body radiotherapy

    No intervention

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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).
    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)

    Secondary Outcome Measures

    Difference between the two arms in liver decompensation while waiting
    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
    Difference between the two arms in perioperative measures
    Proportion of patients with major complications measured in the first 90 days post Liver Transplant
    Difference between the two arms in time to transplant or drop-out
    Time to event (drop-out or transplant) between both groups
    Difference between the two arms in overall survival
    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.
    Difference between the two arms in overall survival
    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
    Difference between the two arms in disease-free survival
    Time-to-event between both groups. Tumor recurrence (new Hepatocellular carcinoma after liver transplant) and patterns of recurrence

    Full Information

    First Posted
    April 5, 2017
    Last Updated
    August 18, 2020
    Sponsor
    University Health Network, Toronto
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03172559
    Brief Title
    Radiotherapy Versus no Intervention in Adult Patients With Hepatocellular Carcinoma Not Eligible for Transarterial Chemoembolization or Ablation Prior to Liver Transplant (RADBRI)
    Acronym
    RADBRI
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2020
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Investigator decided not to pursue the study due to other competing studies.
    Study Start Date
    September 2020 (Anticipated)
    Primary Completion Date
    September 2026 (Anticipated)
    Study Completion Date
    September 2029 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University Health Network, Toronto

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.
    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatocellular Carcinoma
    Keywords
    Stereotactic body radiotherapy, SBRT, Radiotherapy, Bridging therapy, Transplant

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    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).
    Masking
    Outcomes Assessor
    Masking Description
    The data manager uploading the data into a database and the statistician analyzing the data will be blinded to the allocation.
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Stereotactic body radiotherapy
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    No intervention
    Arm Type
    No Intervention
    Arm Description
    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.
    Intervention Type
    Radiation
    Intervention Name(s)
    Stereotactic body radiotherapy
    Other Intervention Name(s)
    SBRT
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    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).
    Description
    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)
    Time Frame
    5 years
    Secondary Outcome Measure Information:
    Title
    Difference between the two arms in liver decompensation while waiting
    Description
    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
    Time Frame
    5 years
    Title
    Difference between the two arms in perioperative measures
    Description
    Proportion of patients with major complications measured in the first 90 days post Liver Transplant
    Time Frame
    5 years
    Title
    Difference between the two arms in time to transplant or drop-out
    Description
    Time to event (drop-out or transplant) between both groups
    Time Frame
    5 years
    Title
    Difference between the two arms in overall survival
    Description
    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.
    Time Frame
    5 years
    Title
    Difference between the two arms in overall survival
    Description
    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
    Time Frame
    5 years
    Title
    Difference between the two arms in disease-free survival
    Description
    Time-to-event between both groups. Tumor recurrence (new Hepatocellular carcinoma after liver transplant) and patterns of recurrence
    Time Frame
    5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Gonzalo Sapisochin, MD
    Organizational Affiliation
    University Health Network, Toronto
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Laura Dawson, MD
    Organizational Affiliation
    University Health Network, Toronto
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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