Biomarker Screening for Liver Cancer

(TRACER Trial)

Recruiting at 13 trial locations

Overseen By Kali Zhou, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Warfarin

Disqualifiers: Child Pugh C, Active cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5.5 years

5500 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, active warfarin use is listed as an exclusion criterion, so you may need to stop taking warfarin to participate.

What data supports the effectiveness of the treatment involving AFP, Alpha-fetoprotein, AFP-L3, GALAD, GALAD Score, GALAD Panel, Liver Ultrasound, Ultrasound Imaging, Sonography, Liver Sonography for liver cancer?

The GALAD score, which includes AFP and AFP-L3, has shown promise in detecting liver cancer early, especially in high-risk patients, and is considered more accurate than liver ultrasound alone. Studies suggest that using the GALAD score in combination with ultrasound can improve early detection of liver cancer, potentially leading to better survival outcomes. ^{1 2 3 4 5}

Is the GALAD score and liver ultrasound safe for humans?

The GALAD score and liver ultrasound are used as diagnostic tools for liver cancer detection and have been studied in various clinical settings. There is no specific safety data mentioned in the research articles, but these methods are generally considered safe as they involve blood tests and imaging, which are non-invasive procedures. ^{1 3 4 5 6}

How is the GALAD treatment different from other liver cancer treatments?

The GALAD treatment is unique because it uses a combination of blood tests and ultrasound to detect liver cancer early, especially in high-risk patients. This approach combines demographic factors and specific proteins in the blood to improve the accuracy of early cancer detection compared to traditional methods. ^{1 3 4 5 7}

Research Team

Amit Singal, MD, MS

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

Adults aged 18-85 with liver cirrhosis of any cause or chronic hepatitis B (with specific risk score) can join this trial. They must be able to consent, have a life expectancy over 6 months, and be eligible for liver cancer surveillance. Exclusions include severe cirrhosis, symptoms or history of certain liver cancers, high AFP levels without clear scans, other active cancers (except some under surveillance), planned MRI/CT-based surveillance, recent serious alcohol-related liver disease.

Inclusion Criteria

I am between 18-85 years old with cirrhosis or chronic hepatitis B and a PAGE-B score over 9.

You are able to give informed consent.

My doctor says I'm eligible for liver cancer surveillance.

Exclusion Criteria

I was diagnosed with a tumor larger than 1 cm in the last 6 months.

I was diagnosed with alcohol-related liver inflammation within the last 3 months.

I am currently experiencing symptoms of acute Wilson disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo semi-annual surveillance using either ultrasound and AFP or GALAD biomarker based on randomization

5.5 years

Semi-annual visits for surveillance

Follow-up

Participants are monitored for safety and effectiveness after the main surveillance period

2.5 years

Extended Follow-up

Extended follow-up to compare incidence of late-stage HCC and reduction in HCC mortality

2.5 years

Treatment Details

Interventions

• AFP
• GALAD
• Liver Ultrasound

Trial Overview The trial is testing two ways to screen for liver cancer in at-risk patients: Arm A uses ultrasound and a blood test called AFP every six months; Arm B uses a biomarker scoring system called GALAD on the same schedule. The goal is to see which method is better at catching late-stage hepatocellular carcinoma early.

Participant Groups

Group I: Arm B: Semi-annual surveillance using GALAD Experimental Treatment 1 Intervention

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

Group II: Arm A: Semi-annual surveillance using liver ultrasound +/- alpha-fetoprotein Active Control 1 Intervention

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

GALAD is already approved in United States, European Union for the following indications:

Approved in United States as GALAD for:

• Hepatocellular carcinoma screening in patients with cirrhosis or chronic hepatitis B infection

Approved in European Union as GALAD for:

• Hepatocellular carcinoma screening in patients with cirrhosis or chronic hepatitis B infection

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Fred Hutchinson Cancer Center

Collaborator

Trials

583

Recruited

1,341,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The GALAD score is a highly effective serum biomarker model for detecting hepatocellular carcinoma (HCC), outperforming liver ultrasound with an area under the ROC curve (AUC) of 0.95 compared to 0.82 for ultrasound.

When combined with ultrasound to create the GALADUS score, the detection performance improved even further, achieving an AUC of 0.98, indicating excellent sensitivity (95%) and specificity (91%) for HCC detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score. Yang, JD., Addissie, BD., Mara, KC., et al.[2022]

In a study involving 168 patients with hepatocellular carcinoma (HCC) and 193 control patients infected with hepatitis C virus (HCV), the ASAP score demonstrated superior diagnostic performance compared to the GALAD score for detecting any stage of HCV-HCC, with an area under the receiver operating characteristic curve (AUROC) of 0.917 versus 0.894.

The ASAP score also outperformed the GALAD score in detecting early-stage HCV-HCC, indicating it may be a more effective tool for screening and surveillance in HCV-infected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASAP Score versus GALAD Score for detection of hepatitis C-related hepatocellular carcinoma: A multicenter case-control analysis. Liu, SY., Li, C., Sun, LY., et al.[2022]

A phase IV biomarker validation study will assess the GALAD score's effectiveness in early detection of hepatocellular carcinoma (HCC) in a cohort of 1,600 patients with advanced fibrosis or cirrhosis over five years in Vietnam and Saudi Arabia.

The study will utilize semi-annual abdominal ultrasounds and dynamic contrast-enhanced MRI to diagnose HCC, aiming to improve survival outcomes through early detection in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score. Truong, TN., Pham, TND., Hoang, LB., et al.[2023]

The GALAD score, which incorporates factors like gender, age, and specific biomarkers, shows potential as a prognostic tool for hepatocellular carcinoma (HCC), indicating that higher scores correlate with decreased survival rates in patients with liver cirrhosis.

In a study of 212 patients, those with confirmed HCC had significantly higher GALAD scores compared to those without HCC, suggesting that this score could help in identifying high-risk patients and improving management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galad Score as a Prognostic Marker for Patients with Hepatocellular Carcinoma. Cagnin, S., Donghia, R., Martini, A., et al.[2023]

Current surveillance methods for hepatocellular carcinoma (HCC) in patients with cirrhosis, such as abdominal ultrasound and α-fetoprotein (AFP) testing, miss over one-third of early-stage tumors, indicating a need for improved detection strategies.

Novel biomarker panels like GALAD and Doylestown Plus show promise for better accuracy in early HCC detection, but further phase III studies are necessary to validate their effectiveness compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doylestown Plus and GALAD Demonstrate High Sensitivity for HCC Detection in Patients With Cirrhosis. Singal, AG., Tayob, N., Mehta, A., et al.[2023]

The American College of Radiology has introduced the Ultrasound Liver Imaging Reporting and Data System (US LI-RADS) to standardize the interpretation and reporting of ultrasound results for hepatocellular carcinoma (HCC), which is crucial for improving patient management.

The US LI-RADS algorithm includes detection and visualization scores that help categorize ultrasound findings, potentially enhancing communication among healthcare providers and leading to better outcomes for patients at high risk for HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

US LI-RADS: ultrasound liver imaging reporting and data system for screening and surveillance of hepatocellular carcinoma. Morgan, TA., Maturen, KE., Dahiya, N., et al.[2022]

The GALAD score is a promising serum biomarker model that effectively diagnoses early hepatocellular carcinoma (HCC), showing significant differences in scores between HCC patients and those with benign cirrhosis (2.65 vs. -0.37).

After local ablative therapy, the GALAD score significantly decreased in patients with well-ablated tumors, indicating its utility in monitoring treatment success, with a sensitivity of 84.48% and specificity of 89.13% for diagnosing early HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of GALAD Score in Diagnosis and Follow-up of Hepatocellular Carcinoma after Local Ablative Therapy. Eletreby, R., Elsharkawy, M., Taha, AA., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

ASAP Score versus GALAD Score for detection of hepatitis C-related hepatocellular carcinoma: A multicenter case-control analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Galad Score as a Prognostic Marker for Patients with Hepatocellular Carcinoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Doylestown Plus and GALAD Demonstrate High Sensitivity for HCC Detection in Patients With Cirrhosis. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

US LI-RADS: ultrasound liver imaging reporting and data system for screening and surveillance of hepatocellular carcinoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Evaluation of GALAD Score in Diagnosis and Follow-up of Hepatocellular Carcinoma after Local Ablative Therapy. [2023]