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HCC Screening Using DNA Methylation Changes in ctDNA

Clinical Trials on Detection of Hepatocellular Carcinoma With Non-invasive Method Based on DNA Methylation of Circulated Tumor DNA, PBMC and T Cells

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT03483922
Enrollment
403
Registered
2018-03-30
Start date
2018-08-20
Completion date
2020-11-01
Last updated
2024-07-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatocellular Carcinoma

Brief summary

Hepatocellular Carcinoma (HCC) is the fifth most common cancer world-wide. It is particularly prevalent in Asia, and its occurrence is highest in areas where hepatitis B is prevalent, indicating a possible causal relationship. Follow up of high-risk populations such as chronic hepatitis patients and early diagnosis of transitions from chronic hepatitis to HCC would improve cure rates. In most cases HCC is detected late resulting in increased mortality and morbidity. The purpose of this study is to develop and test non-invasive biomarkers based on methylation changes in PBMC and circulated tumor DNA in hepatocellular carcinomas patients.

Interventions

DIAGNOSTIC_TESTctDNA methylation in and it's Correlation wth Development and prediction of HCC

Blood sample from patients with HCC, healthy individuals and individuals with hepatitis B will be collected, and DNA will extracted from PBMC and circulated tumor DNA will be subjected to bisulfite conversion. DNA from PBMC DNA will be analyzed with primers developed for the AHNAK-STAP1 genes. Plasma samples will be subjected to EZ direct DNA extraction and bisulfite conversion kit and will be amplified with primers developed to amplify the target regions. DNA will be used for the subsequent PCR amplification with specific primer to generate PCR amplicon for sequencing using a double PCR procedure. The product of PCR reaction will be subjected to indexed MiSeq Next-Generation sequencing that will allow us quantify DNA methylation level.

Sponsors

International Centre for Diarrhoeal Disease Research, Bangladesh
CollaboratorOTHER
HKGepitherapeutics
Lead SponsorINDUSTRY

Study design

Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Confirmed diagnosis of HCC by EASL-EORTC guidelines * Confirmed hepatitis B diagnosis for HepB patients using AASLD practice guidelines.

Exclusion criteria

for HCC: * Cirrhosis, any other known inflammatory disease (bacterial or viral infection with the exception of hepatitis B or C, diabetes, asthma, autoimmune disease, active thyroid disease) which could alter T cells and monocytes characteristics * Other cancers.

Design outcomes

Primary

MeasureTime frameDescription
Calculation of M Scores and HCC Probability Scores6 months to 1 yearWe normalized median methylation values (range 0-100) for 'HCC-detect' (Hepatocellular Carcinoma Detection) and 'HCC-spec' (Hepatocellular Carcinoma Specificity). 'HCC-detect' is derived from CHFR, VASH2, CCNJ, and GRID2IP regions, aiming to broadly identify HCC. Theoretical range is -6.6438 to 8.6438, with observed -3.541 to 7.65; higher scores indicate increased HCC likelihood. 'HCC-spec', focusing on the F12 region, differentiates HCC from 31 other cancers and normal cells, with theoretical range -3.3219 to 6.64385 (observed -3.3219 to 6.6297). Higher scores signify greater HCC specificity. Both scores, modeled via logistic regression in Prism, predict HCC probability, linking higher scores with higher HCC likelihood or specificity

Countries

Bangladesh

Participant flow

Participants by arm

ArmCount
Healthy
Healthy controls
49
Chronic Hepatitis B
Chronic hepatitis B patients
51
HCC Stage 0
HCC patients with Stage 0
2
HCC Stage A
HCC patients with Stage A
32
HCC Stage B
HCC patients with Stage B
86
HCC Stage C
HCC patients with Stage C
106
HCC Stage D
HCC patients with Stage D
76
Total402

Baseline characteristics

CharacteristicHealthyTotalHCC Stage DHCC Stage CHCC Stage BHCC Stage AHCC Stage 0Chronic Hepatitis B
Age, Continuous26.14 years44 years52.45 years49.34 years49.12 years49.15 years62 years28.71 years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
49 Participants402 Participants76 Participants106 Participants86 Participants32 Participants2 Participants51 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Region of Enrollment
Bangladesh
49 Participants402 Participants76 Participants106 Participants86 Participants32 Participants2 Participants51 Participants
Sex: Female, Male
Female
7 Participants68 Participants12 Participants21 Participants14 Participants5 Participants0 Participants9 Participants
Sex: Female, Male
Male
42 Participants334 Participants64 Participants85 Participants72 Participants27 Participants2 Participants42 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
deaths
Total, all-cause mortality
0 / 00 / 00 / 00 / 00 / 00 / 00 / 0
other
Total, other adverse events
0 / 00 / 00 / 00 / 00 / 00 / 00 / 0
serious
Total, serious adverse events
0 / 00 / 00 / 00 / 00 / 00 / 00 / 0

Outcome results

Primary

Calculation of M Scores and HCC Probability Scores

We normalized median methylation values (range 0-100) for 'HCC-detect' (Hepatocellular Carcinoma Detection) and 'HCC-spec' (Hepatocellular Carcinoma Specificity). 'HCC-detect' is derived from CHFR, VASH2, CCNJ, and GRID2IP regions, aiming to broadly identify HCC. Theoretical range is -6.6438 to 8.6438, with observed -3.541 to 7.65; higher scores indicate increased HCC likelihood. 'HCC-spec', focusing on the F12 region, differentiates HCC from 31 other cancers and normal cells, with theoretical range -3.3219 to 6.64385 (observed -3.3219 to 6.6297). Higher scores signify greater HCC specificity. Both scores, modeled via logistic regression in Prism, predict HCC probability, linking higher scores with higher HCC likelihood or specificity

Time frame: 6 months to 1 year

Population: Out of the 402 participants, five did not meet the sequencing depth threshold (i.e., less than 100 reads per gene) for at least one gene, and they were excluded from subsequent analysis.

ArmMeasureValue (MEAN)Dispersion
HealthyCalculation of M Scores and HCC Probability Scores1.113 units on a scaleStandard Deviation 0.3267
Chronic Hepatitis BCalculation of M Scores and HCC Probability Scores1.159 units on a scaleStandard Deviation 0.3508
HCC Stage 0Calculation of M Scores and HCC Probability Scores1.797 units on a scaleStandard Deviation 0.2483
HCC Stage ACalculation of M Scores and HCC Probability Scores1.707 units on a scaleStandard Deviation 0.3615
HCC Stage BCalculation of M Scores and HCC Probability Scores1.839 units on a scaleStandard Deviation 0.2268
HCC Stage CCalculation of M Scores and HCC Probability Scores1.818 units on a scaleStandard Deviation 0.2525
HCC Stage DCalculation of M Scores and HCC Probability Scores1.891 units on a scaleStandard Deviation 0.215

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026