AzTrials
AzTrials

Liver CirrhosisNCT04414956

Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) and Image Tools for Early Detection of Hepatocellular Carcinoma

A study testing AFP-L3, AFP and PIVKA-II in people with Liver Cirrhosis and Hepatocellular Carcinoma, run by Korea University at 15 sites in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

In this study, three biomarkers tests (AFP, AFP-L3 and PIVKA-II) and abdominal sonography or CT scans are performed every 6 months to detect hepatocellular carcinoma (HCC) early in patients with cirrhosis, a high-risk group of HCC. Read more about this study

Who is it for?
Ages 19 to 75 years
What is being tested?
AFP-L3, AFP and PIVKA-II
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,418 participants
Where
15 sitesSouth Korea
Study dates
1 Jul 2016to 28 Feb 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with liver cirrhosis meeting one of the followings:
  • Histologically confirmed liver cirrhosis ii. Imaging findings with liver cirrhosis (liver surface undulation, irregularity, or nodularity by US, CT, or MRI) plus one of followings: liver stiffness measurement ≥ 12.5 kilopascal, esophago-gastric varices, thrombocytopenia (<120,000/mm3), hypoalbuminemia (<3.5 g/dL), splenomegaly ≥12 cm) iii. Imaging findings with liver cirrhosis together with biomarkers suggesting liver cirrhosis (APRI ≥2.0 or fibrosis-4 ≥3.6) iv. Imaging findings with liver cirrhosis with history of hepatic decompensation (ascites, esophago-gastric variceal bleeding, jaundice, hepatic encephalopathy))
  • Expected survival more than 1 year
  • Child Pugh score 5-10 at the time of enrollment
  • Serum creatinine ≤1.5mg/dL
  • Age between 19 and 75 years old
  • No significant underlying medical illness affecting patient's survival
  • Patients available for regular follow-up according to the study protocol

Who cannot join

  • History of HCC
  • AFP >20 ng/mL
  • Hepatic nodule ≥ 1 cm by US or CT Exceptionally, nodules showing characteristic features of benign lesion such as hemangioma or pathologically conformed benign lesion are permitted for study inclusion.
  • Hepatic nodule less than 1 cm on US but imaging findings suggesting HCC by contrast enhanced US, CT, or MRI
  • Child-Pugh score ≥ 11
  • History of liver transplantation
Show all 12Show fewer
  • Expecting liver transplantation within 1 year
  • Hypersensitivity on CT contrast dye
  • Any contraindication for CT
  • Not able to perform abdominal US
  • Other uncontrolled malignancy
  • Patients taking warfarin

Trial locations and contacts

15 sites in 1 country.

Hyung Joon Yim, MD,PhD contact

+82-31-412-6565

gudwns21@korea.ac.kr

Soon Ho Um, MD,PhD contact

+82-2-920-5019

umsh@korea.ac.kr

15 sites in 1 country

South Korea15 sites, 15 recruiting

  • Korea University Ansan Hospital

    Ansan, Gyeonggi-do, 15355

    Hyung Joon Yim, +82-31-412-6565, gudwns21@korea.ac.kr

    Tae Hyung Kim, +82-31-412-4832, lacid@korea.ac.kr

    Recruiting

  • Keimyung University Dongsan Medical Center

    Daegu, 42601

    Byoungkuk Jang

    Recruiting

  • Inje University SangGye Paik Hospital

    Seoul, 01757

    Eileen L. Yoon, mseileen80@gmail.com

    Recruiting

  • Korea University Anam Hospital

    Seoul, 02841

    Soon Ho Um, +82-2-920-6555, umsh@korea.ac.kr

    Recruiting

  • Seoul National University Hospital

    Seoul, 03080

    Yunjoon Kim

    Recruiting

  • Severance Hospital

    Seoul, 03722

    Doyoung Kim

    Recruiting

  • Soonchunhyang University Seoul Hospital

    Seoul, 04401

    Jae Young Jang, jyjang@schmc.ac.kr

    Recruiting

  • Hanyang University Hospital

    Seoul, 04763

    DaeWon Jun

    Recruiting

  • Konkuk University Hospital

    Seoul, 05030

    Wonhyeok Choe

    Recruiting

  • Asan Medical Center

    Seoul, 05505

    Youngseok Yim

    Recruiting

  • Samsung Medical Center

    Seoul, 06351

    Yonghan Paik

    Recruiting

  • The Catholic University of Korea Seoul St.Mary's Hospital

    Seoul, 06591

    Jeong Won Jang

    Recruiting

  • Chung-Ang University Hosptial

    Seoul, 06973

    Hyungjoon Kim

    Recruiting

  • Korea University Guro Hospital

    Seoul, 08308

    Ji Hoon Kim, kjhhepar@naver.com

    Recruiting

  • The Catholic University of Korea Uijeongbu St.Mary's Hospital

    Uijeongbu-si, Gyeonggi-do, 11765

    Changwook Kim

    Recruiting

Other trials in South Korea

About this study

Official title: Clinical Usefulness of Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) With Abdominal Sonography or Computed Tomography for Early Detection of Hepatocellular Carcinoma

In this study, three biomarkers tests (AFP, AFP-L3 and PIVKA-II) and abdominal sonography or CT scans are performed every 6 months to detect hepatocellular carcinoma (HCC) early in patients with cirrhosis, a high-risk group of HCC. The aim of this study is to confirm the early HCC diagnosis rate in patients with cirrhosis and compare the detection efficacy between tests.

Read the detailed description

Early diagnosis of HCC is the most important factor in improving the prognosis of the disease. A surveillance test for early diagnosis of HCC in Korea is to perform alfa fetoprotein (AFP) and abdominal sonography every 6-months in high-risk groups. However, the detection rate of HCC using AFP and abdominal sonography is very low. There are several reports that the combination of the multiple biomarker tests including AFP, AFP L3, and PIVKA-II increased the early HCC detection only one test. Therefore, in the surveillance test for HCC, the combination of three tests with sonography would be helpful in the early diagnosis of HCC. However, there was few prospective large-scale studies about this issue.

Compared with abdominal sonography, contrast-enhanced CT or MRI is more useful in finding intrahepatic lesions of liver cirrhosis. However, there is no evidence data on combining sono/CT and biomarkers could improve the diagnosis for early HCC. Thus, it is essential to verify this prospectively in the real clinical practices to make recommendations based on a high level of evidence in the future. The investigators are conducting a prospective study which examines three biomarker tests and sonography every six months and contrast-enhanced CT annually for HCC surveillance in patients with cirrhosis.

Being tested
AFP-L3, AFP, PIVKA-II, Sonography, CT
Keywords
Liver Cirrhosis, Hepatocellular Carcinoma, Surveillance, AFP-L3, AFP, PIVKA-II, Sonography, CT
Medical subject headings
Liver Cirrhosis, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AFP-L3Diagnostic test

    Also called Lens culinaris agglutinin-reactive fraction of AFP

    AFP-L3 will be tested using serum sample every 6 months.

  • AFPDiagnostic test

    Also called Alpha fetoprotein

    AFP will be tested using serum sample every 6 months.

  • PIVKA-IIDiagnostic test

    Also called Protein induced by vitamin K absence or antagonist-II, des-gamma-carboxy prothrombin

    PIVKA-II will be tested using serum sample every 6 months.

  • SonographyDiagnostic test

    Also called Ultrasound, US

    Sonography will be tested by experts every 6 months.

  • CTDiagnostic test

    Also called Computed tomography

    Contrast-enhanced CT will be tested annually.

Study groups in NCT04414956
Study groupRoleWhat they receive
SurveillanceOtherAll participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually.
Receives: Diagnostic Test: AFP-L3; Diagnostic Test: AFP; Diagnostic Test: PIVKA-II; Diagnostic Test: Sonography; Diagnostic Test: CT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. HCC occurrence

    Detection of HCC occurrence by three biomarkers and two image modalities

    Measured: 3 years after enrollment

Secondary outcomes (1)

  1. Early HCC occurrence

    Detection of HCC less than 2cm

    Measured: 3 years after enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2020
  2. Study start1 Jul 2016
  3. Primary completion30 Jun 2023 (estimated)
  4. Study completion28 Feb 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Screening
Allocation
Not applicable
Intervention model
Single group
Model description
Patients with cirrhosis will receive the surveillance test using three biomarker tests and sonography every six months and contrast-enhanced CT annually
Masking
None (open label)
Enrolment
1,418 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04414956
Sponsor's protocol ID
HCCAFPL3
Status last verified
May 2020
First submitted
20 May 2020
Last updated
4 Jun 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011 Sep 22;365(12):1118-27. doi: 10.1056/NEJMra1001683. No abstract available.

    PubMed 21992124

  • Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver. 2015 May 23;9(3):267-317. doi: 10.5009/gnl14460.

    PubMed 25918260

  • Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol. 2015 Apr 7;21(13):3826-42. doi: 10.3748/wjg.v21.i13.3826.

    PubMed 25852267

  • European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available.

    PubMed 22424438

  • Yim SY, Seo YS, Jung CH, Kim TH, Lee JM, Kim ES, Keum B, Jong YK, An H, Kim JH, Yim HJ, Kim DS, Jeen YT, Yeon JE, Lee HS, Chun HJ, Byun KS, Um SH, Kim CD, Ryu HS. The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years? Liver Int. 2016 Mar;36(3):445-53. doi: 10.1111/liv.12960. Epub 2015 Oct 12.

    PubMed 26352789

  • Sterling RK, Jeffers L, Gordon F, Venook AP, Reddy KR, Satomura S, Kanke F, Schwartz ME, Sherman M. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2009 Jan;7(1):104-13. doi: 10.1016/j.cgh.2008.08.041. Epub 2008 Sep 17.

    PubMed 18849011

  • Taketa K, Sekiya C, Namiki M, Akamatsu K, Ohta Y, Endo Y, Kosaka K. Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology. 1990 Aug;99(2):508-18. doi: 10.1016/0016-5085(90)91034-4.

    PubMed 1694805

  • Taketa K, Endo Y, Sekiya C, Tanikawa K, Koji T, Taga H, Satomura S, Matsuura S, Kawai T, Hirai H. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res. 1993 Nov 15;53(22):5419-23.

    PubMed 7693340

  • Oka H, Saito A, Ito K, Kumada T, Satomura S, Kasugai H, Osaki Y, Seki T, Kudo M, Tanaka M; Collaborative Hepato-Oncology Study Group of Japan. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein. J Gastroenterol Hepatol. 2001 Dec;16(12):1378-83. doi: 10.1046/j.1440-1746.2001.02643.x.

    PubMed 11851836

  • Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, Toshikuni N, Tanaka H, Miyake Y, Matsumoto E, Shiratori Y. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006 Sep;101(9):2038-43. doi: 10.1111/j.1572-0241.2006.00681.x. Epub 2006 Jul 18.

    PubMed 16848811

  • Choi JY, Jung SW, Kim HY, Kim M, Kim Y, Kim DG, Oh EJ. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 2013 Jan 21;19(3):339-46. doi: 10.3748/wjg.v19.i3.339.

    PubMed 23372355

  • Yoon YJ, Han KH, Kim DY. Role of serum prothrombin induced by vitamin K absence or antagonist-II in the early detection of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol. 2009;44(7):861-6. doi: 10.1080/00365520902903034.

    PubMed 19391065

  • Seo SI, Kim HS, Kim WJ, Shin WG, Kim DJ, Kim KH, Jang MK, Lee JH, Kim JS, Kim HY, Kim DJ, Lee MS, Park CK. Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol. 2015 Apr 7;21(13):3928-35. doi: 10.3748/wjg.v21.i13.3928.

    PubMed 25852278

  • Lim TS, Kim DY, Han KH, Kim HS, Shin SH, Jung KS, Kim BK, Kim SU, Park JY, Ahn SH. Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients. Scand J Gastroenterol. 2016 Mar;51(3):344-53. doi: 10.3109/00365521.2015.1082190. Epub 2015 Sep 4.

    PubMed 26340708

  • Di Martino M, De Filippis G, De Santis A, Geiger D, Del Monte M, Lombardo CV, Rossi M, Corradini SG, Mennini G, Catalano C. Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging. Eur Radiol. 2013 Apr;23(4):887-96. doi: 10.1007/s00330-012-2691-z. Epub 2012 Nov 18.

    PubMed 23179521

Questions about this trial

What is this clinical trial studying?

A study testing AFP-L3, AFP and PIVKA-II in people with Liver Cirrhosis and Hepatocellular Carcinoma, run by Korea University at 15 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Hyung Joon Yim, MD,PhD (+82-31-412-6565, gudwns21@korea.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HCC occurrence (time frame: 3 years after enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04414956, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in