Circulating Cell-free DNA-based Epigenetic Biomarker MSEPT9 for Hepatocellular Carcinoma Detection in Cirrhosis (SEPT9-CROSS)

Central Hospital, Nancy, France

Status: Completed

Conditions: Cirrhosis; Hepatocellular Carcinoma

Treatments: Diagnostic Test: "Epi proColon 2.0 CE" test from Epigenomics, Inc (Berlin, Germany)

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT03311152

2017-A01885-48

Details and patient eligibility

About

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 639 cirrhotic patients recruited in the participating centers.

Full 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 630 cirrhotic patients recruited in the participating centers.

Enrollment: 529 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

529 participants in 2 patient groups

HCC-free cirrhotic patients (Controls)

Experimental group

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.

Treatment:

Diagnostic Test: "Epi proColon 2.0 CE" test from Epigenomics, Inc (Berlin, Germany)

HCC-positive cirrhotic patients (Cases)

Experimental group

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.

Treatment:

Diagnostic Test: "Epi proColon 2.0 CE" test from Epigenomics, Inc (Berlin, Germany)