Biomarker Screening for Liver Cancer

(TRACER Trial)

Recruiting at 17 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two methods to screen for liver cancer in individuals with cirrhosis or chronic hepatitis B. One group will undergo regular ultrasounds and blood tests, while the other will use a new blood test called GALAD (a panel of biomarkers) every six months. The goal is to determine which method more effectively detects liver cancer early. Individuals with cirrhosis or chronic hepatitis B who are eligible for cancer screening might be suitable candidates. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, and this research aims to understand its benefits for more patients.

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 is the safety track record for these screening methods?

Research has shown that the GALAD blood test, which considers age, sex, and three specific markers, is safe and well-tolerated. It effectively detects liver cancer in individuals with liver disease. Studies have not reported any major safety concerns with GALAD.

Liver ultrasound, the other method, is a common and widely-used screening tool with a well-established safety profile. Ultrasounds are non-invasive and generally safe, with no major side effects.

Overall, both GALAD and liver ultrasound are safe options for screening liver cancer. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores promising new ways to screen for liver cancer. GALAD, one of the methods under investigation, is unique because it combines various biomarkers to improve detection accuracy, potentially catching cancer earlier than the standard ultrasound, which is often used with or without alpha-fetoprotein (AFP) measurement. Unlike the standard ultrasound approach that relies heavily on imaging, GALAD offers a blood-based analysis, which could be more convenient and less invasive for patients. By comparing these two methods, researchers hope to find out if GALAD can provide a more effective and patient-friendly option for liver cancer surveillance.

What evidence suggests that this trial's screening methods could be effective for liver cancer?

This trial will compare the effectiveness of different surveillance methods for liver cancer. Participants in Arm B will undergo semi-annual surveillance using the GALAD score. Research has shown that the GALAD score effectively detects liver cancer, correctly identifying 89.77% of people with the disease (high sensitivity) and correctly ruling out 97.59% of people without it (high specificity). Other studies have found that GALAD performs as well as an ultrasound in detecting early-stage liver cancer, with an overall accuracy of 0.84 out of 1. This indicates that GALAD is quite reliable in spotting liver cancer, even in its early stages. Additionally, GALAD has proven more effective than the alpha-fetoprotein (AFP) test, which participants in Arm A may receive alongside liver ultrasound, particularly in early detection. ^{1 2 3 4 6}

Who Is on the Research Team?

Amit Singal, MD, MS

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12576547/

Insights into the GALAD score: A new optimal cut-off for ... Using healthy subjects as reference, a GALAD score cut-off of -1.67 identified HCC with a sensitivity of 89.77% and specificity of 97.59%.

2. karger.com karger.com/lic/article/doi/10.1159/000547895/932251/Performance-of-GALAD-GAAD-and-ASAP-for-Early-HCC

Performance of GALAD, GAAD, and ASAP for Early HCC ... GALAD and ultrasound had similar overall performance for early-stage HCC detection with a pooled AUC of 0.84 (95% CI: 0.67–1.00) for GALAD and ...

3. gastrojournal.org gastrojournal.org/article/S0016-5085(24)05460-X/fulltext

A Phase 3 Biomarker Validation of GALAD for the ... Conclusions. GALAD score, compared to AFP, improves the detection of HCC within 12 months before the actual diagnosis.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0973688325001070

Comparison of the GALAD, GAAP, and ASAP Scores for ... Results. The GALAD, GAAP, and ASAP models showed better AUCs (0.876–0.889) in detecting any stage of HCC in patients with CLD than individual ...

5. mayocliniclabs.com mayocliniclabs.com/test-catalog/overview/606585

HCCGS - Overview: Hepatocellular Carcinoma Risk Panel ... The GALAD model has been demonstrated to have higher diagnostic accuracy for the detection of hepatocellular carcinoma (HCC) when compared to the use AFP, AFP- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8844059/

GALAD Demonstrates High Sensitivity for HCC ... A blood-based panel including age, sex, and three biomarkers was able to accurately detect liver cancer in at-risk patients with cirrhosis.