Clinical trial NCT03311152: Circulating Cell-free DNA-based Epigenetic Biomarker MSEPT9 for Hepatocellular Carcinoma Detection in Cirrhosis
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
Overall status: COMPLETED
Phase: NA
Conditions: Hepatocellular Carcinoma
Cirrhosis
Keywords: Hepatocellular carcinoma
Cirrhosis
Circulating epigenetic biomarker
Plasma biomarker
SEPT9
Septin9
DNA methylation biomarker
Circulating DNA methylation biomarker
Alpha-fetoprotein
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: Groupement Interrégional de Recherche Clinique et d'Innovation
name: Epigenomics, Inc
name: New Day Diagnostics
First posted: 2017-10-17
Enrollment: 529
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cross-sectional
Primary purpose: DIAGNOSTIC

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 639 cirrhotic patients recruited in the participating centers.

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 \&#39;omics\&#39; 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.

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).

Primary outcomes:
measure: Presence of hepatocellular carcinoma.
timeFrame: 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 outcomes:
measure: 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).
timeFrame: 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.
Other outcomes:
Locations:
city: Vandoeuvre-lès-Nancy
country: France
facility: University Hospital of Nancy (CHRU de Nancy)
Study officials:
affiliation: University Hospital of Nancy, INSERM UMR_S 1256, Faculty of Medicine of Nancy, University of Lorraine
name: Abderrahim OUSSALAH, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: