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

NCT ID: NCT03172559

Last Updated: 2020-08-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2029-09-30

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).

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Stereotactic body radiotherapy

Intervention Type: RADIATION

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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: RADIATION

Other Intervention Names

SBRT

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gonzalo Sapisochin, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Laura Dawson, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Other Identifiers

17-5329

Identifier Type: -

Identifier Source: org_study_id