National Liver Cancer Screening Trial

NCT ID: NCT06084234

Last Updated: 2025-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

5500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-26

Study Completion Date

2034-12-31

Brief Summary

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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.

Detailed Description

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The TRACER phase IV biomarker study is a randomized trial comparing ultrasound-based screening versus a biomarker-based strategy in patients with cirrhosis. In brief, 5500 patients with cirrhosis from any etiology would be randomized in a 1:1 fashion to Arm A offering semi-annual ultrasound +/- AFP-based screening or Arm B offering semi-annual biomarker-based screening. Randomization will be stratified by site, Child Pugh class (A vs. B), liver disease etiology (viral, non-viral, and non-cirrhotic HBV infection) and sex. Patients will be recruited from 15 sites (mix of tertiary care and large community health systems) over a 3-year period, and reduction in the proportion of late-stage HCC, will be assessed at the end of Year 5.5. If the results are promising, study team will continue extended follow-up and compare the incidence of late-stage HCC between the two arms at Year 8 and reduction in HCC mortality during long term follow up.

Study team will include adult patients, age ≥ 18 years, with Child Pugh class A or B cirrhosis of any etiology or non-cirrhotic chronic hepatitis B virus infection with PAGE-B score \>9. Study team will exclude patients post liver transplantation, patients with Child Pugh C cirrhosis, patients with significant comorbidity and limited life expectancy, and those with history of other malignancy, except non-melanoma skin cancer or indolent tumors, within 3 years prior to enrollment given lack of screening recommendations in those patient populations. Study team will also exclude patients with suspicious liver masses at baseline as well as those with a solid lesion ≥1 cm on ultrasound or AFP ≥20 ng/mL without diagnostic evaluation to exclude HCC. Study team will also exclude patients in whom the provider plans to follow the patient with CT or MRI-based surveillance. GALAD is not recommended in patients with pregnancy or active warfarin use given known impact on biomarker performance, so these patients will be excluded.

At enrollment, study team will record patient demographics and clinical characteristics using a combination of electronic medical records and patient questionnaires. Patients will then be offered semi-annual surveillance as defined by their study arm: ultrasound and AFP for patients in Arm A and the biomarker, GALAD, for patients in Arm B. Repeat surveillance tests will be offered every six months (per assigned arm) for patients with normal surveillance results. Diagnostic evaluation with multi-phasic CT or contrast-enhanced MRI will be recommended for any patients with abnormal screening results. Patients with normal diagnostic testing (i.e., false positive result) will be recommended to return to their assigned surveillance arm. Standardized criteria from the AASLD and LI-RADS will be used to define incident HCC. Study team will use a set of validated surveys (e.g., Psychological Consequences Questionnaire, Decision Regret scale, FACIT-COST) to measure secondary outcomes of interest including psychological and financial harms.

Conditions

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Carcinoma, Hepatocellular Liver Cancer Liver Cirrhosis Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a randomized open-label study comparing US ± AFP vs. GALAD-based surveillance every 6 (± 3-month window) months starting at randomization.
Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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

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

Group Type ACTIVE_COMPARATOR

Liver Ultrasound with or without AFP

Intervention Type DIAGNOSTIC_TEST

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

Arm B: Semi-annual surveillance using GALAD

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

Group Type EXPERIMENTAL

GALAD

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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GALAD

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

Intervention Type DIAGNOSTIC_TEST

Liver Ultrasound with or without AFP

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

1. 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
2. Patient is eligible for HCC surveillance according to treating physician or by the site investigator
3. Able to provide informed consent
4. Life expectancy \>6 months (after consent) as determined by the treating provider or site investigator

Exclusion Criteria

1. Child Pugh C cirrhosis
2. History or clinical symptoms of hepatocellular carcinoma or cholangiocarcinoma
3. 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)
4. 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
5. Newly diagnosed LR-3 greater than or equal to 1 cm within 6 months prior to consent
6. History of LR-4, LR-5, or LR-M on multi-phase CT or contrast-enhanced MRI within 6 months prior to consent
7. 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
8. Patient's provider is planning to use MRI- or CT- based surveillance moving forward
9. History of a transjugular intrahepatic portosystemic shunt (TIPS)
10. History of Fontan associated liver disease or cardiac cirrhosis
11. History of solid organ transplantation
12. Actively listed for liver transplantation
13. Diagnosis of alcohol-associated hepatitis within 3 months prior to consent
14. Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)
15. In patients with primary sclerosing cholangitis (PSC): Current active cholangitis within 90 days prior to consent
16. Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples)
17. In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent
18. Known pregnancy at consent
19. Active warfarin use
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Amit Singal

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Amit Singal, MD, MS

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

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University of Southern California

Los Angeles, California, United States

Site Status RECRUITING

Stanford University

Redwood City, California, United States

Site Status RECRUITING

Kaiser Permanente

Roseville, California, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Indiana University

Indianapolis, Indiana, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Henry Ford Health System

Detroit, Michigan, United States

Site Status RECRUITING

Hennepin Healthcare

Minneapolis, Minnesota, United States

Site Status RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

The Feinstein Institutes, Northwell Health, Inc.

Manhasset, New York, United States

Site Status RECRUITING

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Case Western Reserve University

Cleveland, Ohio, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

UT Southwestern Medical Center and Parkland Hospital

Dallas, Texas, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Amit Singal, MD, MS

Role: CONTACT

214.645.8821

Sneha Deodhar, MS

Role: CONTACT

214.645.1378

Facility Contacts

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Kali Zhou, MD

Role: primary

Paul Kwo, MD

Role: primary

650-723-5135

Jennifer Smart

Role: backup

650-721-8517

Sreepriya Balasubramanian, MD, MPH

Role: primary

916-474-6221

Quyen Chau

Role: backup

4158333468

Rae Davis

Role: primary

Laura Kulik, MD

Role: primary

312-694-1293

Kimberly Sipich

Role: backup

312-694-1293

Sherri Cummins

Role: primary

Megan Michta

Role: primary

Shay Robison

Role: primary

Jessica Peruski

Role: primary

Jose Debes, MD

Role: primary

952-737-9762

Daniel Akah

Role: backup

9527379762

Elizabeth Aby, MD

Role: primary

612-625-8999

Erin Wesley

Role: backup

Dibnain Nanda

Role: primary

Andrew Moon, MD

Role: primary

919-843-5936

Bhagyashree Behera

Role: backup

919-843-5936

Pierre Gholam, MD

Role: primary

216-286-6757

Paul Harris

Role: backup

216.983.5144

Grace Kim

Role: primary

Sneha Deodhar, MS

Role: primary

214-645-1378

Emad Sorial

Role: primary

713-798-7370

Role: backup

Hannah Lee, MD

Role: primary

804-828-4060

Hannah Cook

Role: backup

804-628-9312

References

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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.

Reference Type DERIVED
PMID: 39495136 (View on PubMed)

Other Identifiers

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2U24CA086368-22

Identifier Type: NIH

Identifier Source: secondary_id

View Link

TRACER

Identifier Type: -

Identifier Source: org_study_id

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