HOPE Against Cancer Recurrence in HCC

Phase 4

Not yet recruiting

• Conditions: Liver Transplantation; HCC; Oncological Outcomes

• Registration Number: NCT06717919
• Lead Sponsor: Philipp Dutkowski

Brief Summary

Liver transplantation is often performed to treat liver cancer, or hepatocellular carcinoma (HCC), in patients with impaired liver function due to cirrhosis. A shortcoming, however, is tumor recurrence after transplantation. Approximately 15 % of patients receiving livers develop recurrence and this depends on the quality of the liver received.

Machine liver perfusion, for example, hypothermic oxygenated liver perfusion (HOPE), which means that the organ is perfused with an oxygen-rich fluid in a cold environment before transplantation, is a novel method to improve the quality of livers before implantation. The standard of care is cold storage without perfusion.

The objective of this study is to compare the survival after tumor recurrence of patients after liver transplantation for HCC between perfused and not perfused livers. This study's hypothesis is that survival without tumor recurrence is improved when the liver is perfused before implantation.

The study involves transplant centers worldwide, and adults with HCC waiting for liver transplantation are included. 220 Patients will be recruited within 12 months and then observed for at least 2 years after transplantation. To provide the most valid results, the patients will be randomly allocated to either the organ perfusion group or a control group with standard-of-care cold storage of the organ.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-27
• Status Verified: 2024-12
• Study First Submitted QC: 2024-12-04
• Last Update Submitted: 2024-12-04
• Study First Posted: 2024-12-05
• Last Update Posted: 2024-12-05
• Study Start: 2025-01-01
• Primary Completion: 2028-01-31
• Study Completion: 2028-01-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• Adult recipients (>18y), listed for liver transplantation with documented HCC (Liver Imaging Reporting and Data System (LIRADS) 5 lesion in magnetic resonance imaging or computer tomography of the liver or biopsy proven),
• within up to seven criteria, i.e. HCC with seven as the sum of the diameter of the largest tumour (in cm) and the number of tumours at the time point of liver transplantation,
• written informed consent for the trial. This also includes patients beyond the up to seven criteria after successful downsizing of the HCC

Exclusion Criteria

• Donation after circulatory death (DCD) liver grafts
• Combined liver transplants
• Partial liver transplants
• Combined or mixed hepatocellular cholangiocarcinoma (cHCC-CCC) or pure cholangiocarcinoma or other malignancies in histopathology of the liver explant
• Systemic antitumoural medical treatment with checkpoint inhibitors or multikinase inhibitors
• Post-transplant treatment with mTOR inhibitors
• Acute and unexpected medical contraindications
• Pregnancy
• Cold storage time of > 10 hours (both study arms)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Recurrence free survival	24 months	Post transplant HCC recurrence free survival, i.e. the time interval a patient is alive without HCC recurrence after transplantation, i.e., until either HCC recurrence is observed, or the patient dies from any cause.

Secondary Outcome Measures

Name	Time	Method
HCC recurrence (while alive)	24 months	Time to recurrence of HCC
HCC-related death	24 months	Time to HCC related death
Death from any other causes than HCC	24 months	Time to death not related to HCC
Mean number of circulating tumour deoxyribonucleic acid (DNA) in blood	6 months	This will be measured before transplantation (baseline), at discharge and at 6 months after transplantation. This endpoint will add information on the risk of tumour recurrence by seeding circulating cells.
Mean number of high-mobility-group-protein B1 (HMGB-1) in blood	1 week	This will be measured at the time of transplantation (baseline) and 1 week after transplantation.; This endpoint will add information on danger signalling in both study arms during early and late reperfusion.
Median Rejection Activity Index	6 months	The Rejection Activity Index (RAI) in liver histology (biopsy) is performed at 6 months after transplantation. This endpoint assessed in liver histology (biopsy) will show endothelial and T cell activation in implanted livers within the first months after 6 months.; The RAI can be used to score liver allograft biopsies with acute rejection. The scale is from 1 to 9, higher scores mean more severe signs of rejection.
Liver related complications	24 months	This endpoint will allow to assess the association between initial graft injury and liver specific complications in both study arms.

Trial Locations

Locations (1)

University Hospital Basel; 🇨🇭 Basel, BS, Switzerland