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

NCT03172559 | Withdrawn DMC

• 1 other identifier: 17-5329
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatocellular Carcinoma

Keywords

Stereotactic body radiotherapy; SBRT; Radiotherapy; Bridging therapy; Transplant

Outcome Measures

Primary Outcomes (1)

• 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)

  5 years

Secondary Outcomes (6)

• Difference between the two arms in liver decompensation while waiting

  5 years

• Difference between the two arms in perioperative measures

  5 years

• Difference between the two arms in time to transplant or drop-out

  5 years

• Difference between the two arms in overall survival

  5 years

• Difference between the two arms in overall survival

  5 years

Study Arms (2)

Stereotactic body radiotherapy

EXPERIMENTAL

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

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.

Interventions

Stereotactic body radiotherapy 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.

Also known as: SBRT

Stereotactic body radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Gonzalo Sapisochin, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Laura Dawson, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The data manager uploading the data into a database and the statistician analyzing the data will be blinded to the allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: April 5, 2017
• First Posted: June 1, 2017
• Study Start: September 1, 2020
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2029
• Last Updated: August 20, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share