HOPE Against Cancer Recurrence in HCC (HOPE4Cancer)

December 15, 2025 updated by: Philipp Dutkowski

Hypothermic Oxygenated Perfusion (HOPE) Against Cancer Recurrence in HCC Liver Transplantation - International Multicentre Parallel Group Interventional RCT

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

220

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Recruiting
        • Medical University of Innsbruck
        • Contact:
        • Principal Investigator:
          • Stefan Schneeberger, Prof. Dr.
      • Vienna, Austria, 1090
        • Recruiting
        • Medical University of Vienna
        • Contact:
        • Contact:
          • Phone Number: +43 140 400 687 30
        • Principal Investigator:
          • Thomas Soliman
  • Belgium
      • Leuven, Belgium, 3000
        • Recruiting
        • University Hospitals Leuven
        • Contact:
        • Principal Investigator:
          • Diethard Monbaliu, Dr.
      • Woluwe-Saint-Lambert, Belgium, 1200
        • Recruiting
        • Institut de Recherche Expérimentale et Clinique (IREC) UCLouvain (Brussels)
        • Contact:
        • Principal Investigator:
          • Eliano Bonaccorsi Riani, Dr.
  • Czechia
      • Prague, Czechia, 14021
        • Recruiting
        • Institute for Clinical and Experimental Medicine (IKEM) (Prague)
        • Contact:
        • Principal Investigator:
          • Jiri Fronek, Prof
  • Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Copenhagen University Hospital
        • Contact:
        • Principal Investigator:
          • Hans Christian Pommergaard, Prof. Dr.
  • France
      • Lyon, France, 69004
        • Not yet recruiting
        • Hôpital de la Croix-Rousse (Lyon)
        • Contact:
        • Principal Investigator:
          • Xavier Müller, Prof
  • Germany
      • Essen, Germany, 45122
        • Not yet recruiting
        • Universitätsklinikum Essen
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ulf Neumann, Prof
      • Hamburg-Eppendorf, Germany, 20246
        • Not yet recruiting
        • University Medical Centre Hamburg-Eppendorf
        • Contact:
        • Principal Investigator:
          • Uta Herden, Prof. Dr.
      • Hanover, Germany, 30626
        • Not yet recruiting
        • Hannover Medical School
        • Contact:
        • Principal Investigator:
          • Cornelius van Beekum, Dr
      • Heidelberg, Germany, 69120
        • Not yet recruiting
        • University of Heidelberg
        • Contact:
        • Principal Investigator:
          • Deniz Uluk, Dr
      • Mainz, Germany, 55131
        • Not yet recruiting
        • University of Mainz
        • Contact:
        • Principal Investigator:
          • Jens Mitler, Dr
      • München, Germany, 81377
        • Not yet recruiting
        • University of Munich Grosshadern
        • Contact:
        • Principal Investigator:
          • Dionysios Koliogiannis
  • Italy
      • Milan, Italy, 20133
      • Milan, Italy, 20162
        • Not yet recruiting
        • ASST Grande Ospedale Metropolitano Niguarda (Milan)
        • Contact:
        • Principal Investigator:
          • Riccardo de Carlis, Dr.
      • Padua, Italy, 35128
        • Not yet recruiting
        • Padova University Hospital
        • Contact:
          • Umberto Cillo, Prof
          • Phone Number: +39 0496366593
          • Email: cillo@unipd.it
        • Principal Investigator:
          • Umberto Cillo, Prof.
      • Rome, Italy, 00168
        • Not yet recruiting
        • Gemelli University Hospital
        • Contact:
        • Principal Investigator:
          • Marco Maria Pascale, Prof
      • Udine, Italy, 33100
        • Recruiting
        • University of Udine
        • Contact:
        • Principal Investigator:
          • Umberto Baccarani, Prof
  • Lithuania
      • Kaunas, Lithuania, 50009
        • Not yet recruiting
        • Lithuanian University of Health Sciences
        • Contact:
        • Principal Investigator:
          • Povilas Ignatavičius, Ass-Prof
  • Netherlands
      • Groningen, Netherlands, 9713
        • Not yet recruiting
        • University of Groningen and University Medical Centre Groningen
        • Contact:
        • Principal Investigator:
          • Vincent De Meijer, Prof. Dr
      • Rotterdam, Netherlands, 3015
        • Not yet recruiting
        • University Medical Centre Rotterdam - Erasmus University Medical Center
        • Contact:
        • Principal Investigator:
          • Jeroen De Jonge, Dr.
  • Norway
      • Oslo, Norway, 0450
        • Not yet recruiting
        • Oslo University Hospital
        • Contact:
        • Principal Investigator:
          • Morten Hagness, Dr
  • Poland
      • Gdansk, Poland, 80-210
        • Recruiting
        • Department of Surgical Oncology, Transplant Surgery and General Surgery, Medical University of Gdańsk
        • Contact:
        • Principal Investigator:
          • Piotr Domagola, Prof
      • Warsaw, Poland, 02-097
        • Not yet recruiting
        • Medical University of Warsaw
        • Contact:
        • Principal Investigator:
          • Michal Grat, Prof
  • Portugal
      • Lisbon, Portugal, 1069-166
        • Not yet recruiting
        • Centro Hepato-Bilio-Pancreático e de Transplantação (CHBPT)
        • Contact:
          • Hugo Pinto Marques, Prof
        • Principal Investigator:
          • Hugo Pinto Marques
  • Spain
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Vall d'Hebron Barcelona Hospital Campus
        • Contact:
        • Principal Investigator:
          • Mireira Caralt Barba, Prof
  • Sweden
      • Stockholm, Sweden, 17177
        • Recruiting
        • Karolinska Institutet (Stockholm)
        • Contact:
        • Principal Investigator:
          • Gabriel Oniscu, Prof
  • Switzerland
      • Geneva, Switzerland, 1205
        • Recruiting
        • Hopitaux Universitaires de Geneve
        • Contact:
        • Principal Investigator:
          • Philippe Compagnon, Prof. Dr.
    • Canton of Basel-City
      • Basel, Canton of Basel-City, Switzerland, 4031
        • Not yet recruiting
        • Clarunis - University Digestive Health Care
        • Contact:
        • Principal Investigator:
          • Philipp Dutkowski, Prof. Dr.
    • Canton of Zurich
      • Zurich, Canton of Zurich, Switzerland, 8091
        • Not yet recruiting
        • University Hospital Zurich
        • Principal Investigator:
          • Andreas Kremer, Prof. Dr.
        • Contact:
  • United Kingdom
      • Birmingham, United Kingdom, B15 2GW
        • Not yet recruiting
        • University Hospitals Birmingham
        • Contact:
        • Principal Investigator:
          • Rebeca Sanabria Mateos, Dr
      • Leeds, United Kingdom, LS97TF
        • Not yet recruiting
        • Leeds Teaching Hospitals NHS Trust
        • Contact:
        • Principal Investigator:
          • Barbara Fiore, Dr
      • London, United Kingdom, NW3 2QG
        • Not yet recruiting
        • The Royal Free Hospital (London)
        • Contact:
        • Principal Investigator:
          • Joerg-Matthias Pollok, Prof
      • London, United Kingdom, SE5 9RS
        • Not yet recruiting
        • King's College Hospital (London)
        • Contact:
        • Principal Investigator:
          • Miriam Cortes Cerisuelo, Dr
      • Newcastle, United Kingdom, NE7 7DN
        • Not yet recruiting
        • Freeman Hospital (Newcastle)
        • Contact:
        • Principal Investigator:
          • Rodrigo Figueiredo
  • United States
    • New York
      • New York, New York, United States, 07103
        • Not yet recruiting
        • Rutgers New Jersey Medical School (New York)
        • Principal Investigator:
          • James Guarerra, Prof
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Not yet recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • Andrea Schlegel, Prof
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Conventional cold storage
Conventional cold storage at 4°C will be performed with precooled preservation solution according to local standard of care. For cold storage at the Swiss centres, IGL-1 (Institute George Lopez) is used for cold storage. Liver transplant centres in other European countries, use mainly three other storage solutions (Histidine trypophan-ketoglutarat, HTK and University of Wisconsin, UW solution, Celsior) in accordance to their national guidelines.
Procedure: Conventional cold storage
Conventional cold storage at 4°C will be performed with precooled preservation solution according to local standard of care. For cold storage at the Swiss centres, IGL-1 (Institute George Lopez) is used for cold storage. Liver transplant centres in other European countries, use mainly three other storage solutions (Histidine trypophan-ketoglutarat, HTK and University of Wisconsin, UW solution, Celsior) in accordance to their national guidelines.
Experimental: Hypothermic oxygenated perfusion

All study centres will use either VitaSmart, Liver assist or Perlife devices for machine liver perfusion, with a pressure controlled hypothermic oxygenated liver perfusion through the portal vein (HOPE) or through the portal vein and the hepatic artery (DHOPE), targeting a flow rate between 200-250 ml/min at a pressure of 3 mmHg, and a perfusate temperature between 8-12°C. The perfusate consists of 3L re-circulating Belzer MPS® (Bridge to Life Ltd.) with an active oxygenation (70-110 kPa). The minimum perfusion duration is defined at 2 hours, while perfusion is generally continued until the recipient hepatectomy is completed. The perfusion will exclusively be performed in the recipient centre after initial cold storage and bench preparation of the liver for implantation.

The perfusion devices are routinely used in all participating centres (VitaSmart, Bridge to Life®, Liver Assist, XVIVO®, Perlife, Aferitica®).
Procedure: Hypothermic oxygenated perfusion
All study centres will use either VitaSmart, Liver assist or Perlife devices for machine liver perfusion, with a pressure controlled hypothermic oxygenated liver perfusion through the portal vein (HOPE) or through the portal vein and the hepatic artery (DHOPE), targeting a flow rate between 200-250 ml/min at a pressure of 3 mmHg, and a perfusate temperature between 8-12°C. The perfusate consists of 3L re-circulating Belzer MPS® (Bridge to Life Ltd.) with an active oxygenation (70-110 kPa). The minimum perfusion duration is defined at 2 hours, while perfusion is generally continued until the recipient hepatectomy is completed. The perfusion will exclusively be performed in the recipient centre after initial cold storage and bench preparation of the liver for implantation. The perfusion devices are routinely used in all participating centres.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence free survival
Time Frame: 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.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HCC recurrence (while alive)
Time Frame: 24 months
Number of HCC recurrences
24 months
HCC recurrence (while alive)
Time Frame: 24 months
Time to recurrence of HCC
24 months
HCC-related death
Time Frame: 24 months
Death related to HCC
24 months
HCC-related death
Time Frame: 24 months
Time to HCC related death
24 months
Death from any other causes than HCC
Time Frame: 24 months
Death not related to HCC
24 months
Death from any other causes than HCC
Time Frame: 24 months
Time to death not related to HCC
24 months
Mean number of circulating tumour deoxyribonucleic acid (DNA) in blood
Time Frame: 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.
6 months
Mean number of high-mobility-group-protein B1 (HMGB-1) in blood
Time Frame: 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.
1 week
Median Rejection Activity Index
Time Frame: 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.
6 months
Liver related complications
Time Frame: 24 months
This endpoint will allow to assess the association between initial graft injury and liver specific complications in both study arms.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Philipp Dutkowski

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2025

Primary Completion (Estimated)

January 31, 2028

Study Completion (Estimated)

January 31, 2028

Study Registration Dates

First Submitted

November 27, 2024

First Submitted That Met QC Criteria

December 4, 2024

First Posted (Actual)

December 5, 2024

Study Record Updates

Last Update Posted (Actual)

December 16, 2025

Last Update Submitted That Met QC Criteria

December 15, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 221622

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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