HOPE Against Cancer Recurrence in HCC

Официальное название

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

Обзор

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.

Вмешательства

• Процедура 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 m
• Процедура 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.

Первичные конечные точки

• Recurrence free survival [Срок оценки: 24 months]

Вторичные конечные точки (10)

• HCC recurrence (while alive) [Срок оценки: 24 months]
• HCC recurrence (while alive) [Срок оценки: 24 months]
• HCC-related death [Срок оценки: 24 months]
• HCC-related death [Срок оценки: 24 months]
• Death from any other causes than HCC [Срок оценки: 24 months]
• Death from any other causes than HCC [Срок оценки: 24 months]
• Mean number of circulating tumour deoxyribonucleic acid (DNA) in blood [Срок оценки: 6 months]
• Mean number of high-mobility-group-protein B1 (HMGB-1) in blood [Срок оценки: 1 week]
• Median Rejection Activity Index [Срок оценки: 6 months]
• Liver related complications [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Германия · 6 центров

• Universitätsklinikum Essen — Essen
• University Medical Centre Hamburg-Eppendorf — Hamburg-Eppendorf
• Hannover Medical School — Hanover
• University of Heidelberg — Heidelberg
• University of Mainz — Mainz
• University of Munich Grosshadern — München

Италия · 5 центров

• Milano Institutio Nazionale dei Tumori (Milan) — Milan
• ASST Grande Ospedale Metropolitano Niguarda (Milan) — Milan
• Padova University Hospital — Padova
• Gemelli University Hospital — Rome
• University of Udine — Udine

Великобритания · 5 центров

• University Hospitals Birmingham — Birmingham
• Leeds Teaching Hospitals NHS Trust — Leeds
• The Royal Free Hospital (London) — London
• King's College Hospital (London) — London
• Freeman Hospital (Newcastle) — Newcastle

Швейцария · 3 центра

• Clarunis - University Digestive Health Care — Basel
• University Hospital Zurich — Zurich
• Hôpitaux universitaires de Genève — Geneva

США · 2 центра

• Rutgers New Jersey Medical School (New York) — New York
• Cleveland Clinic — Cleveland

Австрия · 2 центра

• Medical University of Innsbruck — Innsbruck
• Medical University of Vienna — Vienna

Бельгия · 2 центра

• University Hospitals Leuven — Leuven
• Institut de Recherche Expérimentale et Clinique (IREC) UCLouvain (Brussels) — Woluwe-Saint-Lambert

Нидерланды · 2 центра

• University of Groningen and University Medical Centre Groningen — Groningen
• University Medical Centre Rotterdam - Erasmus University Medical Center — Rotterdam

Польша · 2 центра

• Department of Surgical Oncology, Transplant Surgery and General Surgery, Medical Universit — Gdansk
• Medical University of Warsaw — Warsaw

Чехия · 1 центр

• Institute for Clinical and Experimental Medicine (IKEM) (Prague) — Prague

Дания · 1 центр

• Copenhagen University Hospital — Copenhagen

Франция · 1 центр

• Hôpital de la Croix-Rousse (Lyon) — Lyon

Литва · 1 центр

• Lithuanian University of Health Sciences — Kaunas

Норвегия · 1 центр

• Oslo University Hospital — Oslo

Португалия · 1 центр

• Centro Hepato-Bilio-Pancreático e de Transplantação (CHBPT) — Lisbon

Испания · 1 центр

• Vall d'Hebron Barcelona Hospital Campus — Barcelona

Швеция · 1 центр

• Karolinska Institutet (Stockholm) — Stockholm

Публикации

• Eden J, Muller PC, Kuemmerli C, Peters F, Litke T, Kranich A, Kremer AE, von Felten S, Dutkowski P; HOPE4Cancer Trial Investigators. Hypothermic oxygenated perfusion (HOPE) against cancer recurrence after liver transplantation for hepatocellular carcinoma-study protocol for an international multicenter randomized controlled trial (HOPE4Cancer). Trials. 2025 Sep 26;26(1):369. doi: 10.1186/s13063-02 PMID 41013675

Идентификаторы

NCT: NCT06717919 · 221622

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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