NCT06084234

Brief Summary

The National Liver Cancer Screening Trial is an adaptive randomized phase IV Trial comparing ultrasound-based versus biomarker-based screening in 5500 patients with cirrhosis from any etiology or patients with chronic hepatitis B infection. Eligible patients will be randomized in a 1:1 fashion to Arm A using semi-annual ultrasound and AFP-based screening or Arm B using semi-annual screening using GALAD alone. Randomization will be stratified by sex, enrolling site, Child Pugh class (A vs. B), and HCC etiology (viral vs. non-viral). Patients will be recruited from 15 sites (mix of tertiary care and large community health systems) over a 3-year period, and the primary endpoint of the phase IV trial, reduction in late-stage HCC, will be assessed after 5.5 years.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5,500

participants targeted

Target at P75+ for phase_4

Timeline
105mo left

Started Dec 2023

Longer than P75 for phase_4

Geographic Reach
1 country

18 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress21%
Dec 2023Dec 2034

First Submitted

Initial submission to the registry

October 10, 2023

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 16, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

December 26, 2023

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2029

Expected
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2034

Last Updated

November 26, 2025

Status Verified

November 1, 2025

Enrollment Period

6 years

First QC Date

October 10, 2023

Last Update Submit

November 25, 2025

Conditions

Keywords

Hepatocellular carcinoma surveillanceGALADAlpha Fetoprotein

Outcome Measures

Primary Outcomes (1)

  • Proportion of HCC detected at late stage

    Proportion of HCC detected at a late stage, defined as HCC beyond Milan Criteria (one tumor less than or equal to 5 cm or 2-3 tumors each less than or equal to 3 cm, in the absence of vascular invasion or extra-hepatic metastases)

    5.5 years

Secondary Outcomes (7)

  • HCC Screening utilization

    5.5 years

  • Proportion of HCC detected at a late-stage (defined based on BCLC stage)

    5.5 years

  • Incidence of late-stage HCC

    8 years

  • Proportion of HCC cases that receive Curative therapy

    5.5 years

  • Number of participants who encountered screening related physical harm

    5.5 years

  • +2 more secondary outcomes

Study Arms (2)

Arm A: Semi-annual surveillance using liver ultrasound +/- alpha-fetoprotein

ACTIVE COMPARATOR

Participants in this arm will undergo current standard of care surveillance procedures i.e. liver ultrasound with or without alpha fetoprotein (AFP) measurement.

Diagnostic Test: Liver Ultrasound with or without AFP

Arm B: Semi-annual surveillance using GALAD

EXPERIMENTAL

For participants in this arm, study team will order GALAD measurement every 6 months +/- 3 months.

Diagnostic Test: GALAD

Interventions

GALADDIAGNOSTIC_TEST

GALAD is a 3 biomarker panel incorporating AFP, AFP-L3% and DCP (all FDA approved), with patient age and sex.

Arm B: Semi-annual surveillance using GALAD

This intervention consists of current standard of care ultrasound based surveillance with or without alpha-fetoprotein measurement.

Arm A: Semi-annual surveillance using liver ultrasound +/- alpha-fetoprotein

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult patients ages 18-85 with cirrhosis from any etiology or with chronic hepatitis B with a PAGE-B score greater than 9 within 12 months of enrollment
  • Patient is eligible for HCC surveillance according to treating physician or by the site investigator
  • Able to provide informed consent
  • Life expectancy \>6 months (after consent) as determined by the treating provider or site investigator

You may not qualify if:

  • Child Pugh C cirrhosis
  • History or clinical symptoms of hepatocellular carcinoma or cholangiocarcinoma
  • History of solid nodule on baseline ultrasound (i.e., lesion 1cm or greater) within 9 months prior to consent without subsequent diagnostic CT/MRI demonstrating benign nature)
  • AFP \>20 ng/mL within 6 months prior to consent, in the absence of a contrast-enhanced CT or MRI within 6 months of AFP (before or after) level demonstrating lack of suspicious liver lesions
  • Newly diagnosed LR-3 greater than or equal to 1 cm within 6 months prior to consent
  • History of LR-4, LR-5, or LR-M on multi-phase CT or contrast-enhanced MRI within 6 months prior to consent
  • Presence of another active cancer besides non-melanomatous skin cancer or indolent cancer under active surveillance (e.g., prostate cancer or renal cell carcinoma) within the 2 years prior to consent
  • Patient's provider is planning to use MRI- or CT- based surveillance moving forward
  • History of a transjugular intrahepatic portosystemic shunt (TIPS)
  • History of Fontan associated liver disease or cardiac cirrhosis
  • History of solid organ transplantation
  • Actively listed for liver transplantation
  • Diagnosis of alcohol-associated hepatitis within 3 months prior to consent
  • Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)
  • In patients with primary sclerosing cholangitis (PSC): Current active cholangitis within 90 days prior to consent
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

University of Southern California

Los Angeles, California, 90089, United States

RECRUITING

Stanford University

Redwood City, California, 94063, United States

RECRUITING

Kaiser Permanente

Roseville, California, 95661, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94117, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Hennepin Healthcare

Minneapolis, Minnesota, 55415, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

The Feinstein Institutes, Northwell Health, Inc.

Manhasset, New York, 11030, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Case Western Reserve University

Cleveland, Ohio, 44106, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

UT Southwestern Medical Center and Parkland Hospital

Dallas, Texas, 75390, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77021, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

NOT YET RECRUITING

Related Publications (1)

  • Singal AG, Parikh ND, Kanwal F, Marrero JA, Deodhar S, Page-Lester S, Lopez C, Feng Z, Tayob N. National Liver Cancer Screening Trial (TRACER) study protocol. Hepatol Commun. 2024 Nov 4;8(11):e0565. doi: 10.1097/HC9.0000000000000565. eCollection 2024 Nov 1.

MeSH Terms

Conditions

Carcinoma, HepatocellularLiver NeoplasmsLiver CirrhosisHepatitis B

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and SymptomsBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis

Study Officials

  • Amit Singal, MD, MS

    University of Texas Southwestern Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
SCREENING
Intervention Model
PARALLEL
Model Details: This is a randomized open-label study comparing US ± AFP vs. GALAD-based surveillance every 6 (± 3-month window) months starting at randomization.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

October 10, 2023

First Posted

October 16, 2023

Study Start

December 26, 2023

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2034

Last Updated

November 26, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will not share

Locations