Characterization of Methylation Patterns in Hepatocellular Carcinoma

This study is being performed as part of the development process of the Liver EpiCheck test which includes the identification of different methylation profiles in HCC (hepatocellular carcinoma) patients compare to cancer free control in blood samples

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma; Cirrhosis; Hepatocellular Cancer
• Intervention / Treatment: Procedure: Blood collection

Detailed Description

This is a prospective, multi-center, observational study aimed to collect blood samples and de-identified clinical data from subjects diagnosed with HCC (cases arm) and subjects with high risk for HCC which are undergoing routine surveillance for HCC.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel
    • Ha'Emek Medical Center
  • Haifa, Israel
    • Rambam Medical Center
  • Haifa, Israel
    • Carmel Medical Center
  • Ramat Gan, Israel
    • Sheba Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects who have already been diagnosed with liver cancer, however did not yet undergo any surgery, ablation, embolization or any other treatment for this cancerous lesion (including, but not limited to systemic therapies) will be enlisted into the study as the Case group.

In addition, blood samples will be obtained from participants without cancer, who are considered in high risk for HCC; those subjects will be recruited from outpatient units or from Health Management Organization involved in routine surveillance for HCC in high risk subjects.

Description

Inclusion Criteria - Case Group:

• Age ≥ 22 years
• Subjects who are willing and able to provide written informed consent
• Subjects with confirmed diagnosis of HCC, naïve to tumor directed therapy

Exclusion Criteria - Case Group:

• Subjects with current cancer of any kind, other than hepatocellular carcinoma
• Subjects with a history of cancer of any kind (including hepatocellular carcinoma), other than non-melanoma skin cancer completely resected
• Coinfection with HIV
• Prior solid organ transplant

Inclusion Criteria - Control Group:

• Age ≥ 22 years
• Subjects who are willing and able to provide written informed consent

• Subjects diagnosed with one of the following:

  i. Subjects with HCV and cirrhosis ii. Subjects with HBV and cirrhosis iii. Non-cirrhotic chronic HBV subjects at intermediate or high risk of HCC, according to EASL Clinical Practice Guidelines for the management of hepatocellular carcinoma iv. Subjects with Non-Alcoholic Fatty Liver Disease (NAFLD) with cirrhosis. v. Cirrhotic patients due to any other reasons, including alcohol disease

• Subjects currently undergoing surveillance for hepatocellular carcinoma
• HCC surveillance imaging (e.g., US, CT, MRI) performed within 3 months prior to baseline visit
• Subjects with compensated liver function as measured by Child-Pugh Score A or B7 without ascites (all measures should be from the last three months)

Exclusion Criteria - Control Group:

• Subjects with current cancer of any kind, other than hepatocellular carcinoma
• Subjects with a history of cancer of any kind (including hepatocellular carcinoma), other than non-melanoma skin cancer completely resected
• Coinfection with HIV
• Prior solid organ transplant
• Current substance abuse

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases Group; Subjects who have already been diagnosed with liver cancer, however did not yet undergo any surgery, ablation, embolization or any other treatment for this cancerous lesion (including, but not limited to systemic therapies)	Procedure: Blood collection; Peripheral blood will be collected via routine venipuncture procedure
Control Group; Cancer free subjects with high risk to development HCC. High risk subjects include the following: Subjects with HCV (hepatitis C virus) and cirrhosis; Subjects with HBV (hepatitis B virus) and cirrhosis; Non-cirrhotic chronic HBV subjects at intermediate or high risk of HCC, according to EASL (European Association for the Study of the Liver) Clinical Practice Guidelines for the management of hepatocellular carcinoma; Subjects with NAFLD (Non-Alcoholic Fatty Liver Disease) with cirrhosis; Cirrhotic patients due to any other reasons, including alcohol disease	Procedure: Blood collection; Peripheral blood will be collected via routine venipuncture procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To collect blood samples and clinical data in order to characterize methylation patterns that will discriminate between HCC and normal hepatic tissue	To collect blood samples and clinical data in order to characterize methylation patterns that will discriminate between HCC and normal hepatic tissue	60 months
To develop a molecular blood test that will be able to detect HCC based on change in methylation patterns between HCC and normal hepatic tissue	To develop a molecular blood test that will be able to detect HCC based on change in methylation patterns between HCC and normal hepatic tissue	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver EpiCheck Performance	To assess the performance of the Liver EpiCheck in terms of (1) Sensitivity (2) Specificity (3) NPV(negative predictive value) and (4) PPV (positive predictive value)	60 months

Collaborators and Investigators

• Sponsor: Nucleix Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 13, 2018
• Primary Completion (ACTUAL): February 1, 2021
• Study Completion (ACTUAL): February 1, 2021

Study Registration Dates

• First Submitted: February 9, 2020
• First Submitted That Met QC Criteria: February 9, 2020
• First Posted (ACTUAL): February 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 6, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; HCC; Cirrhosis; Methylation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Fibrosis; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: Liver-RND-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be share with other researchers. The statistical analysis will be performed by the study sponsor

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No