HOPE Against Cancer Recurrence in HCC (HOPE4Cancer)

Philipp Dutkowski

Status and phase: Enrolling; Phase 4

Conditions: Liver Transplantation; Oncological Outcomes; HCC

Treatments: Procedure: Hypothermic oxygenated perfusion; Procedure: Conventional cold storage

Study type: Interventional

Funder types: Other

Identifiers

NCT06717919

221622

Details and patient eligibility

About

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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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220 participants in 2 patient groups

Conventional cold storage

Active Comparator group

Description:

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.

Treatment:

Procedure: Conventional cold storage

Hypothermic oxygenated perfusion

Experimental group

Description:

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®).

Treatment:

Procedure: Hypothermic oxygenated perfusion