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

Primary Purpose

Hepatocellular Carcinoma, Cirrhosis

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
"Epi proColon 2.0 CE" test from Epigenomics, Inc (Berlin, Germany)
Sponsored by
Central Hospital, Nancy, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Hepatocellular Carcinoma focused on measuring Hepatocellular carcinoma, Cirrhosis, Circulating epigenetic biomarker, Plasma biomarker, SEPT9, Septin9, DNA methylation biomarker, Circulating DNA methylation biomarker, Alpha-fetoprotein

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • University Hospital of Nancy (CHRU de Nancy)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

HCC-free cirrhotic patients (Controls)

HCC-positive cirrhotic patients (Cases)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Presence of hepatocellular carcinoma.
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.

Secondary Outcome Measures

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).
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.

Full Information

First Posted
October 5, 2017
Last Updated
June 8, 2022
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
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1. Study Identification

Unique Protocol Identification Number
NCT03311152
Brief Title
Circulating Cell-free DNA-based Epigenetic Biomarker mSEPT9 for Hepatocellular Carcinoma Detection in Cirrhosis
Acronym
SEPT9-CROSS
Official Title
Diagnostic Accuracy of the Circulating Cell-free DNA-based Epigenetic Biomarker mSEPT9 for Hepatocellular Carcinoma Detection Among Cirrhotic Patients: the SEPT9-CROSS Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 12, 2018 (Actual)
Primary Completion Date
February 12, 2023 (Anticipated)
Study Completion Date
February 12, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the 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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Cirrhosis
Keywords
Hepatocellular carcinoma, Cirrhosis, Circulating epigenetic biomarker, Plasma biomarker, SEPT9, Septin9, DNA methylation biomarker, Circulating DNA methylation biomarker, Alpha-fetoprotein

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Cross-sectional biomarker Phase II design
Masking
ParticipantCare ProviderInvestigator
Masking Description
The index test (mSEPT9) will be reported at the final step of the research, at time of data analysis.
Allocation
Non-Randomized
Enrollment
530 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HCC-free cirrhotic patients (Controls)
Arm Type
Experimental
Arm Description
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.
Arm Title
HCC-positive cirrhotic patients (Cases)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
"Epi proColon 2.0 CE" test from Epigenomics, Inc (Berlin, Germany)
Other Intervention Name(s)
Plasma mSEPT9 test
Intervention Description
The mSEPT9 assay consists of DNA extraction from plasma, bisulfite conversion of DNA, purification of bis-DNA, and real-time PCR.
Primary Outcome Measure Information:
Title
Presence of hepatocellular carcinoma.
Description
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.
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.
Secondary Outcome Measure Information:
Title
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).
Description
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.
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Abderrahim OUSSALAH, MD, PhD
Phone
+33 (0)3 83 15 36 29
Email
a.oussalah@chru-nancy.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abderrahim OUSSALAH, MD, PhD
Organizational Affiliation
University Hospital of Nancy, INSERM UMR_S 1256, Faculty of Medicine of Nancy, University of Lorraine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Nancy (CHRU de Nancy)
City
Vandoeuvre-lès-Nancy
ZIP/Postal Code
54511
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abderrahim OUSSALAH, MD, PhD
Phone
+33 (0)3 83 15 36 29
Email
a.oussalah@chru-nancy.fr
First Name & Middle Initial & Last Name & Degree
Abderrahim OUSSALAH, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jean-Louis GUÉANT, MD,DSc,AGAF
First Name & Middle Initial & Last Name & Degree
Jean-Pierre BRONOWICKI, MD, PhD
First Name & Middle Initial & Last Name & Degree
Valérie LAURENT, MD, PhD
First Name & Middle Initial & Last Name & Degree
Ahmet AYAV, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

Circulating Cell-free DNA-based Epigenetic Biomarker mSEPT9 for Hepatocellular Carcinoma Detection in Cirrhosis

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