SBRT for Liver Cancer Before Liver Transplantation

NCT04186234 | Active Not Recruiting

• 1 other identifier: UW 15-191
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is the second commonest cause of cancer death worldwide. It is the third leading cause of cancer death in Hong Kong. Liver transplantation (LT) is the curative treatment of choice for HCC as it has the advantage of removing the tumour and also the premalignant cirrhotic liver. Milan (solitary tumour \<5cm, or up to 3 tumours, each \<3cm) and University of California San Francisco (UCSF) criteria (solitary tumour ≤6.5cm, up to 3 tumours with none \>4.5cm, and total tumour diameter ≤8cm) provide the benchmark requirements for LT, at which a 5-year survival of \>70% and recurrence rate ranging from 5-15% can be achieved. However, organ shortage and waiting time for liver grafts remain the greatest obstacles for deceased donor liver transplantation (DDLT). It has been reported that the waiting list dropout rate is 7 to 11% at 6 months and 38% at 12 months. Several therapeutic procedures including transarterial chemoembolisation (TACE) and stereotactic body radiation therapy (SBRT) have been studied as bridging therapy before DDLT, aiming at reducing waiting list dropout rate and recurrence after LT, and improving post-transplant survival. The investigators have carried out a prospective study on HCC patients treated with bridging SBRT before LT. The investigators used dual tracer (18F-fluorodeoxyglucose \[FDG\] and 11carbon-acetate \[ACC\]) positron-emission tomography with integrated computed tomography (PET-CT) and magnetic resonance imaging with gadoxetate disodium as baseline and subsequent imaging assessment before and after SBRT, hoping the PET-CT can help better identify those who benefit from SBRT and to prioritise those with poor response so that they can be better channeled to LT.

Conditions

Liver Cancer; Liver Transplant Disorder

Keywords

Liver cancer; Stereotactic body radiation therapy; Bridging therapy; Liver transplantation

Outcome Measures

Primary Outcomes (2)

• Progression-free survival

  Progression-free survival

  36 months

• Best objective response

  Best objective response

  36 months

Secondary Outcomes (1)

• Overall survival

  36 months

Other Outcomes (2)

• Toxicity profile

  36 months

• Changes in Child-Pugh status

  36 months

Study Arms (1)

Stereotactic body radiation therapy

EXPERIMENTAL

Stereotactic body radiation therapy of 35 to 50 Grays in 5 fractions over 5 to 14 days.

Radiation: Stereotactic body radiation therapy

Interventions

Stereotactic body radiation therapy RADIATION

Stereotactic body radiation therapy of 30 to 50 Grays in 5 fractions before liver transplantation

Stereotactic body radiation therapy

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or radiologically confirmed HCC. For radiological diagnosis of HCC, a contrast-enhanced computed tomography or magnetic resonance imaging is mandatory to demonstrate the early arterial enhancement in arterial phase and contrast washout in the porto-venous phase on the imaging
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorisation (e.g. Health Insurance Portability and Accountability Act in the US, Euripean Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
• HCC lesions with Milan criteria or University of San Francisco criteria for LT
• Be \>/= 18 years of age on day of signing informed consent
• Have a performance status of 0 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• A stage C or earlier HCC based on Barcelona Clinic Liver Cancer (BCLC) staging system.
• A Child-Pugh of 8 or less.
• Adequate serum hematological functions defined as:
• Absolute neutrophil count (ANC) ≥1.0 x 10\^9/l
• Platelet ≥20 x 10\^9/l
• Haemoglobin ≥8 g/dL
• Adequate serum biochemistry functions defined as:
• Serum bilirubin ≤5.0 x institutional upper limit of normal (ULN). \<\<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\>
• AST (SGOT)/ALT (SGPT) ≤6 x institutional upper limit of normal
• Albumin ≥25g/litre

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter.
• Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study.
• Has had a prior monoclonal antibody, immunotherapy or immune checkpoint inhibitors before recruitment into this study.
• Has had prior chemotherapy or targeted small molecule therapy (including sorafenib, lenvatinib, or other anti-vascular endothelial growth factor inhibitor) before recruitment into this study.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy
• Has a history of prior solid organ transplants with or without any episodes of graft-versus-host disease.
• Has a history of allogeneic bone marrow transplantation and peripheral stem cell rescue, with or without any episodes of graft-versus-host disease.
• Has known extra-hepatic metastases.
• Has known carcinomatous meningitis (also known as leptomeningeal carcinomatosis)
• Has an active infection requiring intravenous systemic therapy or hospital admission.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment.
• Untreated hepatitis B infection. Patients with chronic hepatitis B infection (defined as HBsAg positive) are eligible if they have started anti-viral therapy for at least 1 month and is continuing anti-viral treatment throughout the whole duration of this study.
• Has experienced Grade 4 toxicity on treatment with prior radiation if done before.
• Prior systemic therapy utilising an anti CTLA-4 or PD-1/PD-L1 agent or other forms of immunotherapy.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Department of Clinical Oncology, Queen Mary Hospital

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Victor Lee, MD

  Department of Clinical Oncology, The University of Hong Kong, Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Inapplicable
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Model Details: Stereotactic body radiation therapy as bridging therapy before liver transplantation for hepatocellular carcinoma

Study Record Dates

• First Submitted: December 1, 2019
• First Posted: December 4, 2019
• Study Start: January 1, 2015
• Primary Completion: October 31, 2023
• Study Completion: December 31, 2025
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)