National Liver Cancer Screening Trial (TRACER)

March 27, 2024 updated by: Amit Singal, University of Texas Southwestern Medical Center
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

5500

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90089
        • Recruiting
        • University of Southern California
        • Contact:
          • Kali Zhou, MD
        • Principal Investigator:
          • Kali Zhou, MD
      • San Francisco, California, United States, 94117
        • Recruiting
        • University of California, San Francisco
        • Principal Investigator:
          • Neil Mehta, MD
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University
        • Principal Investigator:
          • Naga Chalasani, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Not yet recruiting
        • Massachusetts General Hospital
        • Contact:
          • Irun Bhan, MD
        • Principal Investigator:
          • Irun Bhan, MD
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Principal Investigator:
          • Neehar Parikh, MD, MS
        • Contact:
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health System
        • Principal Investigator:
          • Reena Salgia, MD
        • Contact:
    • New York
      • Manhasset, New York, United States, 11030
        • Recruiting
        • The Feinstein Institutes, Northwell Health, Inc.
        • Principal Investigator:
          • Sanjaya Satapathy, MBBS, MS
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern Medical Center and Parkland Hospital
        • Principal Investigator:
          • Amit Singal, MD, MS
        • Contact:
      • Houston, Texas, United States, 77021
        • Recruiting
        • Baylor College of Medicine
        • Contact:
          • Sara Fares
        • Contact:
        • Principal Investigator:
          • Fasiha Kanwal, MD, MSHS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Patient must meet all of the following 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:

Patient will be excluded for any of the following 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
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.
Experimental: Arm B: Semi-annual surveillance using GALAD
For participants in this arm, study team will order GALAD measurement every 6 months +/- 3 months.
Diagnostic test: GALAD
GALAD is a 3 biomarker panel incorporating AFP, AFP-L3% and DCP (all FDA approved), with patient age and sex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of HCC detected at late stage
Time Frame: 5.5 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
HCC Screening utilization
Time Frame: 5.5 years
Defined as proportion time covered by screening; each completed screening test (US +/- AFP or GALAD) will provide up to six months of coverage (numerator) divided by the total follow-up for each patient.
5.5 years
Proportion of HCC detected at a late-stage (defined based on BCLC stage)
Time Frame: 5.5 years
Defined as HCC beyond BCLC stage A (single tumor of any size without vascular invasion or extrahepatic spread; or 2-3 tumors equal to or less than 3 cm each, without vascular invasion or extrahepatic spread)
5.5 years
Incidence of late-stage HCC
Time Frame: 8 years
Defined as incidence of HCC (extended follow-up) beyond Milan Criteria or BCLC stage A
8 years
Number of participants who encountered screening related physical harm
Time Frame: 5.5 years
Physical harms will be defined as count of participants in receipt of diagnostic imaging for false positive or indeterminate results.
5.5 years
Number of participants who encountered screening related financial harm
Time Frame: 5.5 years
Financial harms will be defined by direct costs (charges for all screening and diagnostic testing and co-pays) and indirect costs (e.g., travel and lost wages)
5.5 years
Number of participants who encountered screening related Psychological harm
Time Frame: 5.5 years
Count of participants who encountered Psychological harms that includes cancer-specific worry and decisional regret.
5.5 years
Proportion of HCC cases that receive Curative therapy
Time Frame: 5.5 years
Defined as count of participants in receipt of liver transplantation, surgical resection, local ablative therapy, or radiation segmentectomy
5.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

National Cancer Institute (NCI)
Baylor College of Medicine
University of Pennsylvania
Dana-Farber Cancer Institute
University of Michigan
Fred Hutchinson Cancer Center

Investigators

  • Principal Investigator: Amit Singal, MD, MS, UT Southwestern Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 26, 2023

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2034

Study Registration Dates

First Submitted

October 10, 2023

First Submitted That Met QC Criteria

October 10, 2023

First Posted (Actual)

October 16, 2023

Study Record Updates

Last Update Posted (Actual)

March 29, 2024

Last Update Submitted That Met QC Criteria

March 27, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRACER
  • 2U24CA086368-22 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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