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

2026년 5월 27일 업데이트: 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.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

300

단계

  • 해당 없음

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

  • 벨기에
      • Antwerp, 벨기에
        • 모병
        • UZA
        • 연락하다:
        • 수석 연구원:
          • Timon Van Damme, MD, PhD
      • Hasselt, 벨기에
      • Kortrijk, 벨기에
      • Roeselare, 벨기에

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

  • 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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 기초 과학
  • 할당: 무작위화되지 않음
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
간섭 없음: 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.
다른: 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.
다른: 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.
다른: 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.
다른: 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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Spatial orientation
기간: 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
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Universitaire Ziekenhuizen KU Leuven

협력자

Flemish institute of biotechnology (VIB)

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2025년 3월 4일

기본 완료 (추정된)

2029년 1월 1일

연구 완료 (추정된)

2032년 1월 1일

연구 등록 날짜

최초 제출

2025년 2월 6일

QC 기준을 충족하는 최초 제출

2026년 5월 27일

처음 게시됨 (실제)

2026년 6월 3일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 6월 3일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 5월 27일

마지막으로 확인됨

2026년 5월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • S69815

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

간세포 암종(HCC)에 대한 임상 시험

Blood and tissue sample에 대한 임상 시험

유사한 임상시험 검색

스폰서 및 공동 작업자

건강 상태

약물 개입

CROs by country

CROs in Belgium

정황

희귀 질병

약물 개입

식이 보충제

스폰서 / 협력자

위치

구독하다