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Improving the Use of Immunotherapy to Treat Liver Cancer (IO-MARC)

27 mei 2026 bijgewerkt door: Universitaire Ziekenhuizen KU Leuven

Optimizing and Improving Immunotherapy for Hepatocellular Carcinoma: the IO-MARC Study

This project targets patients with a form of primary liver cancer, specifically "hepatocellular carcinoma". This disease often develops in the context of a chronically diseased liver, caused by viral infections, excessive alcohol consumption, or fatty liver. Primarily due to the rise of the latter risk factor, liver cancer is one of the few cancer types whose incidence continues to increase globally, year after year. As a result, liver cancer has become the third most common cause of cancer-related deaths worldwide. There exists a significant challenge in reducing the disease on all fronts: prevention, diagnosis, and treatment.

This research aims to personalize the treatment of liver cancer patients, tailoring it to the individual. More specifically, this research seeks to identify patients with immunotherapy-sensitive liver cancer by biomarkers before treatment begins. Determining whether a tumor is immunotherapy-sensitive is internationally recognized as one of the most important challenges within this condition. Based on a combination of existing laboratory techniques on tumor tissue and/or blood, the investigators seek to predict the likelihood of this treatment's success before initiating it. With this knowledge, the investigators could recommend alternative treatments to patients with tumors that are unresponsive. This way, they would also avoid exposure to the side effects of an ineffective therapy.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Multicentric, low-interventional with retrospective and prospective components. No investigational medicinal product (IMP) is involved.

Patient management is standard of care. Prospective tissue collection is done at the time of standard of care diagnostic biopsies or surgical procedures. Blood collection is performed at the time of routine lab evaluations. No additional study visits, venipunctures or other procedures are expected. Three hundred patients will be included in the following three cohorts:

  • Cohort 1 - 120 patients: archival tumor tissue of 120 patients previously treated with systemic therapies for hepatocellular carcinoma in the last 5 years will be collected.
  • Cohort 2 - 90 patients: prospective tumor tissue and blood samples of 90 patients with advanced HCC and candidate for systemic therapy will be collected.
  • Cohort 3 - 90 patients: prospective tumor tissue and blood samples of 90 patients with early HCC and candidate for local treatment will be collected.

Objectives:

  • Aim 1: Spatial orientation of cell types of interest in the tumor microenvironment (TME) of HCC using a variety of techniques: multiplex immune histochemistry, spatial proteomics and spatial transcriptomics. Samples from early versus advanced HCC will be used.
  • Aim 2: Identification of shared T-cell receptor sequences between PBMCs and tumor tissue using RNA and TCR sequencing. Exploration of the degree of TCR sharing in early and advanced HCC.
  • Aim 3: Collecting starting material for TWISTAR, aiming to identify tumor antigens in HCC using a transcriptome-wide screen for T cell antigens.

Our analysis will be powered to identify a difference in progression-free survival between the biomarker positive and negative population with a hazard ratio of 0.6 with a power of 75% and an alpha of 0.05, provided that about 30% of samples are biomarker positive. The historical samples of patients treated with a TKI will serve as a control group to detect an interaction with the biomarker and the treatment effect.

Studietype

Ingrijpend

Inschrijving (Geschat)

300

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • België
      • Antwerp, België
        • Werving
        • UZA
        • Contact:
        • Hoofdonderzoeker:
          • Timon Van Damme, MD, PhD
      • Hasselt, België
      • Kortrijk, België
      • Roeselare, België

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

  • General inclusion Criteria:

    1. Male or female, age > 18 years
    2. Diagnosis or suspected diagnosis of hepatocellular carcinoma based on imaging

  • Specific inclusion criteria cohort 1 (retrospective/prospective data may be applicable):

    1. Pathologically confirmed HCC
    2. Treated with systemic treatment [tyrosine kinase inhibitor (TKI) or immunotherapy (ICI)] in the last 7 years and follow-up data (at least one imaging on treatment) available until 01/01/2025
    3. Biopsy obtained between 01/01/2018 until 01/01/2025
    4. Left-over tissue from previous diagnostic biopsies or resection specimens available
    5. Time between biopsy and initiation of systemic treatment < 1 year
    6. Ability to sign informed consent for secondary use of archival tissue and data collection for study-specific research for patients who are alive

  • Specific inclusion criteria cohort 2 (aHCC & prospective):

    1. Suspicion of hepatocellular carcinoma (imaging criteria or recurrent disease of previously treated HCC)
    2. Indication for tumor biopsy per standard of care
    3. Eligible for systemic treatment (any) after pathological confirmation of HCC
    4. Ability to sign informed consent for primary use of tissue and blood samples and data collection for study-specific research

  • Specific inclusion criteria cohort 3 (eHCC & prospective):

    1. Suspicion of hepatocellular carcinoma (imaging criteria or recurrent disease of previously treated HCC)
    2. Indication for local treatment (resection or ablation)

    3. Ability to sign informed consent for primary use of tissue and blood samples and for data collection for study-specific research

      Due to the observational nature of this study, participation in other (interventional) clinical trials is permitted, if biological materials can be collected per protocol.

  • General exclusion criteria:

    1. Poor liver function and/or performance status which prohibits active treatment
    2. Pathologically proven other malignancies of the liver, including primary cholangiocarcinoma or liver metastases
    3. Treatment plan other than systemic treatment or local treatment (resection or ablation), such as TACE, TARE, liver transplantation

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Geen tussenkomst: Cohort 1

Cohort 1 (observational):

  • Collection of leftover archival tumour tissue of patients with advanced HCC treated with systemic therapies.
  • No blood collection.
  • Retrospective and prospective collection of data.
Ander: Cohort 2

Cohort 2 (advanced HCC):

  • Prospective collection of tumour tissue at the time of standard of care biopsy from advanced HCC patients prior to initiation of a systemic treatment (max 2 needle biopsy cylinders).
  • Additional collection of leftover archival tissue from previous biopsies or resection specimens is possible.
  • Prospective collection of blood samples at two timepoints (prior to start of systemic treatment and prior to the 2nd therapy cycle). Maximum 30ml of blood per timepoint (3x10ml EDTA tubes).
  • Retrospective and prospective collection of data.
Ander: Blood and tissue sample
Prospective collection of additional blood and tissue samples for study-specific analyses at specific timepoints, at the same time as routine procedures.
Ander: Cohort 3
  • Prospective collection of tumour tissue at the time of standard of care biopsy (max 2 needle biopsy cylinders) or surgical treatment (resection or ablation; 2 surgical biopsies or a piece of the resection specimen) from early HCC patients.
  • Additional collection of leftover archival tissue from previous biopsies or resection specimens is possible.
  • Prospective collection of blood samples at one timepoint (prior to resection or ablation). Maximum 30ml of blood per timepoint (3x10ml EDTA tubes).
  • Retrospective and prospective collection of data.
Ander: Blood and tissue sample
Prospective collection of additional blood and tissue samples for study-specific analyses at specific timepoints, at the same time as routine procedures.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Spatial orientation
Tijdsspanne: Through study completion, an average of 6 months
Spatial orientation of cell types of interest in the tumour microenvironment (TME) of HCC using a variety of techniques: multiplex IHC, spatial proteomics and spatial transcriptomics. Samples from early (cohort 3) and advanced HCC (cohort 2) will be used.
Through study completion, an average of 6 months
TCR sharing
Tijdsspanne: Through study completion, an average of 6 months
Identification of shared TCR sequences between PBMCs and tumor tissue using RNA and TCR sequencing. Exploration of the degree of TCR sharing in early and advanced HCC.
Through study completion, an average of 6 months
Antigen identification
Tijdsspanne: Through study completion, an average of 6 months
The investigators will use tumor tissue and PBMC to construct an antigenic landscape of advanced HCC. To achieve this goal the investigators will use a unique technique called Transcriptome-Wide Screening for T cell Antigen Research (TWISTAR).
Through study completion, an average of 6 months
Biomarker validation
Tijdsspanne: 12 months after tissue acquisition

This study will be used to validate two candidate predictive biomarkers (CD45RA effector-memory CD8 T-cells/PDL1-expressing CXCL10+ macrophages) AND TCR sharing between tumor and blood in relation to response to immunotherapy in HCC.

The investigators will compare the biomarker positive and biomarker negative groups in terms of progression-free survival and overall survival (Kaplan-Meier time-to-event) in the context of known prognostic clinical variables (multivariable cox proportional hazards model).
12 months after tissue acquisition

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Universitaire Ziekenhuizen KU Leuven

Medewerkers

Flemish institute of biotechnology (VIB)

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

4 maart 2025

Primaire voltooiing (Geschat)

1 januari 2029

Studie voltooiing (Geschat)

1 januari 2032

Studieregistratiedata

Eerst ingediend

6 februari 2025

Eerst ingediend dat voldeed aan de QC-criteria

27 mei 2026

Eerst geplaatst (Werkelijk)

3 juni 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

3 juni 2026

Laatste update ingediend die voldeed aan QC-criteria

27 mei 2026

Laatst geverifieerd

1 mei 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • S69815

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Klinische onderzoeken op Hepatocellulair carcinoom (HCC)

Klinische onderzoeken op Blood and tissue sample

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