Circulating Cell-free DNA-based Epigenetic Biomarker mSEPT9 for Hepatocellular Carcinoma Detection in Cirrhosis (SEPT9-CROSS)

June 8, 2022 updated by: Central Hospital, Nancy, France

Diagnostic Accuracy of the Circulating Cell-free DNA-based Epigenetic Biomarker mSEPT9 for Hepatocellular Carcinoma Detection Among Cirrhotic Patients: the SEPT9-CROSS Study

Prospective evaluation of the circulating cell-free DNA-based epigenetic biomarker (mSEPT9) through a cross-sectional biomarker phase II design. The aim of the SEPT9-CROSS study is to assess the diagnostic accuracy of the plasma mSEPT9 biomarker in a large-scale study of 530 cirrhotic patients recruited in the Nancy University Hospital.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. This is strikingly the case in hepatocellular carcinoma (HCC) which represent the most common primary malignant tumor of the liver. Alpha-fetoprotein (AFP) has been widely used as a diagnostic marker of HCC; however, according to international guidelines (AASLD, EASL), AFP is unsufficiently sensitive or unsufficiently specific for use in a screening assay. Aberrantly methylated DNA sequences frequently occur in tumors and are detected in the circulation of cancer patients by polymerase chain reaction (PCR). SEPT9 is a significant epi-driver gene in liver carcinogenesis. The SEPT9 gene is a key regulator of cell division and tumor suppressor whose hypermethylation is associated with carcinogenesis. SEPT9 is involved in the onset of rat hepatocarcinogenesis and SEPT9-promoter hypermethylation was reported in HCC in man. SEPT9 expression is turned on in cells throughout the body and absent or diminished by aberrant promoter methylation in several types of cancer. Through an initial proof-of-concept pilot study from France and an independent replication study from Germany, we showed that the circulating cell-free DNA methylation-based epigenetic biomarker mSEPT9 is a promising plasma biomarker for diagnosing HCC in cirrhotic patients. The aim of the SEPT9-CROSS study is to confirm the diagnostic accuracy of the biomarker in a large-scale study of 530 cirrhotic patients recruited in the Nancy University Hospital.

Study Type

Interventional

Enrollment (Anticipated)

530

Phase

  • Not Applicable

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

  • France
      • Vandoeuvre-lès-Nancy, France, 54511
        • Recruiting
        • University Hospital of Nancy (CHRU de Nancy)
        • Contact:
        • Principal Investigator:
          • Abderrahim OUSSALAH, MD, PhD
        • Sub-Investigator:
          • Jean-Louis GUÉANT, MD,DSc,AGAF
        • Sub-Investigator:
          • Jean-Pierre BRONOWICKI, MD, PhD
        • Sub-Investigator:
          • Valérie LAURENT, MD, PhD
        • Sub-Investigator:
          • Ahmet AYAV, MD, PhD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA

  • Patient aged 18 and over.
  • Patient with a diagnosis of cirrhosis (alcohol, HBV, HBC, NASH, hemochromatosis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) with or without hepatocellular carcinoma (for each arm).
  • Affiliation to the French Social Security System (Health Insurance)

NON-INCLUSION CRITERIA FOR CASES :

  • Malignant liver tumor other than HCC: cholangiocarcinoma, hepatic metastasis of a carcinoma (e.g., colorectal adenocarcinoma);
  • History of HCC treated by surgical resection, focal destruction [radiofrequency, stereotactic radiotherapy (CYBERKNIFE®)], arterial chemoembolization, or radioembolization within the last five years.

NON-INCLUSION CRITERIA FOR CASES AND CONTROLS:

  • Legal protection measures;
  • Pregnant woman;
  • Hemodialysis, ongoing (possibility of interference with the test);
  • Presence of associated cancer (e.g., colorectal adenocarcinoma, urothelial carcinoma, breast carcinoma, etc.) since less than five years;
  • Presence of a hematological malignancy (no time limit).

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: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HCC-free cirrhotic patients (Controls)
Cirrhotic patients enrolled in an HCC screening program by abdominal ultrasound and AFP every six months and followed at the Department of Hepatology of the University Hospital of Nancy. Each patient included will undergo a diagnostic test called "Epi proColon 2.0 CE" from Epigenomics, Inc (Berlin, Germany) also known as Plasma mSEPT9 test.
Diagnostic test: "Epi proColon 2.0 CE" test from Epigenomics, Inc (Berlin, Germany)
The mSEPT9 assay consists of DNA extraction from plasma, bisulfite conversion of DNA, purification of bis-DNA, and real-time PCR.
Other Names:
  • Plasma mSEPT9 test
Experimental: HCC-positive cirrhotic patients (Cases)
Cirrhotic patients followed at the Department of Hepatology of the University Hospital of Nancy who presents an HCC according to the AASLD guidelines. Each patient included will undergo a diagnostic test called "Epi proColon 2.0 CE" from Epigenomics, Inc (Berlin, Germany) also known as Plasma mSEPT9 test.
Diagnostic test: "Epi proColon 2.0 CE" test from Epigenomics, Inc (Berlin, Germany)
The mSEPT9 assay consists of DNA extraction from plasma, bisulfite conversion of DNA, purification of bis-DNA, and real-time PCR.
Other Names:
  • Plasma mSEPT9 test

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of hepatocellular carcinoma.
Time Frame: The diagnosis of HCC will be based on overall patient's evaluation including clinical, biological and imaging workup which will be carried out during the consultation and/or the three months preceding or following the inclusion consultation.
The diagnosis of hepatocellular carcinoma will be based on the guidelines of the American Association for the Study of Liver Diseases (AASLD) (Hepatology. 2011;53:1020-2). The adjudicating physicians will be blinded to patient results associated with the mSEPT9 test.
The diagnosis of HCC will be based on overall patient's evaluation including clinical, biological and imaging workup which will be carried out during the consultation and/or the three months preceding or following the inclusion consultation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of early hepatocellular carcinoma. Early hepatocellular carcinoma will be defined as a tumor smaller than 30 mm according to Kudo M (Liver Cancer. 2013;2:69-72).
Time Frame: The diagnosis will be based on an overall patient's evaluation including clinical, biological and imaging workup which will be carried out during the consultation and/or the three months preceding or following the inclusion consultation.
The diagnosis of hepatocellular carcinoma will be based on the guidelines of the American Association for the Study of Liver Diseases (AASLD) (Hepatology. 2011;53:1020-2). The adjudicating physicians will be blinded to patient results associated with the mSEPT9 test.
The diagnosis will be based on an overall patient's evaluation including clinical, biological and imaging workup which will be carried out during the consultation and/or the three months preceding or following the inclusion consultation.

Collaborators and Investigators

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

Sponsor

Central Hospital, Nancy, France

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France
Groupement Interrégional de Recherche Clinique et d'Innovation
Epigenomics, Inc

Investigators

  • Principal Investigator: Abderrahim OUSSALAH, MD, PhD, University Hospital of Nancy, INSERM UMR_S 1256, Faculty of Medicine of Nancy, University of Lorraine

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)

February 12, 2018

Primary Completion (Anticipated)

February 12, 2023

Study Completion (Anticipated)

February 12, 2023

Study Registration Dates

First Submitted

October 5, 2017

First Submitted That Met QC Criteria

October 10, 2017

First Posted (Actual)

October 17, 2017

Study Record Updates

Last Update Posted (Actual)

June 9, 2022

Last Update Submitted That Met QC Criteria

June 8, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-A01885-48

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Final report, publication in a peer review journal. Main data and supplemental data.

IPD Sharing Time Frame

Final report after data completion.

IPD Sharing Access Criteria

After the publication of study results.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

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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