A Protocol of the Canadian Prospective Study for Hepatocellular Carcinoma Surveillance Using Biomarkers

NCT02272504 | Completed

• 1 other identifier: WLS 13-6926
• Study Type: observational
• Target: 2,500
• Locations: 1 country
• Sites: 2

Brief Summary

The objective of this study is to evaluate the clinical effectiveness of biomarkers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), for surveillance program patients whose hepatocellular carcinoma (HCC) development may be potentially missed by ultrasound (US). This study expects to demonstrate that addition of biomarkers will increase the detection rate by at least 10%.

Conditions

Cirrhosis; Chronic Liver Diseases

Keywords

HCC; AFP; AFP-L3; DCP; Surveillance; biomarkers

Outcome Measures

Primary Outcomes (1)

• Biomarker assays exceeding threshold

  Biomarker assay levels that exceed threshold will trigger diagnostic imaging for HCC. Ultrasound imaging indicating a suspicious nodule may also trigger diagnostic imaging.

  Every 6 months until HCC is detected or up to 4 years

Secondary Outcomes (1)

• Surveillance until HCC development and detection

  Up to 4 years

Study Arms (2)

Standard of care arm

Chronic liver disease patients who are under going standard of care surveillance for the development of HCC as defined by AASLD guidelines.

Biomarker Arm

Chronic liver disease patients who are under going standard of care surveillance for the development of HCC as defined by AASLD guidelines plus the addition of biomarker assays (AFP, AFP-L3 and DCP) every 6 months.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients who are at risk for the development of HCC as identified by the prior presence of chronic liver disease and cirrhosis.

You may qualify if:

• Patient who is able and willing to comply with study procedures, and signed and dated informed consent is obtained.
• Patients aged 18 years and older.
• Hep B Risk Score \> 8 (table 1)
• Table 1 Variable Risk Score Variable Risk Score Male 2 ALT \<15 0 Female 0 ALT 15-44 1 Age 30-34 0 ALT \> 45 2 Age 35-39 1 HBeAg+ve 0 Age 40-44 2 Anti-HBe-positive 2 Age 45-49 3 HBV DNA \<300 copies/mL 0 Age 50-54 4 HBV DNA 300-9999 copies/mL 0 Age 55-59 5 HBV DNA 104 -99,000 copies/mL 3 Age 60-65 6 HBV DNA 105 - 999,999 copies/mL 5 HBV DNA \> 106 copies/mL 4

You may not qualify if:

• Patients who have confirmed HCC by CT/MRI when they enrolled. Patients who have previously had HCC but have been treated and have been recurrence free for 5 years are eligible.
• Patients with the other cancer(s)
• Pregnant Women
• Patients who have known diagnosis of mental incapacitation that affects their ability to consent.
• Patients who are likely to be transplanted within 1 year or MELD score greater than 20.
• Patients with total or direct bilirubin \> 3x upper limit of normal
• Patients with uncontrollable ascites
• Glomerular Filtration Rate less than 60.
• Patients with ≥ Grade II of hepatic encephalopathy
• Patients who are being treated with warfarin (DCP test values are affected by warfarin)
• Patients who have any contraindication to any of the study procedures, products used or its constituents (e.g., renal failure or contrast allergy).
• Patients who suffer from claustrophobia or who have other contraindications to MRI
• Patients with cirrhosis who were successfully treated for hepatitis C more than 3 years prior. However, patients who are on study who are treated for their hepatitis C may continue in the study.

Sponsors & Collaborators

• Wako Life Sciences: lead

Study Sites (2)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (1)

• Hirode G, Zangneh HF, Cerocchi O, Khalili K, El-Karim LA, Kandel C, Vecchio M, Winick J, Mori Y, Yamada H, Janssen HLA, Hansen BE, Sherman M, Feld JJ. Utility of Serum Biomarkers in Addition to Ultrasound for Early Detection of Hepatocellular Carcinoma in High-Risk Patients: A Randomized Controlled Trial. Gastroenterology. 2026 Jan 20:S0016-5085(25)05993-1. doi: 10.1053/j.gastro.2025.09.010. Online ahead of print.

  PMID: 41556856 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Frozen Serum samples will be retained

MeSH Terms

Conditions

Fibrosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Feld Jordan, MD

  Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2014
• First Posted: October 23, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2020
• Study Completion: February 1, 2021
• Last Updated: July 23, 2024

Record last verified: 2024-07

Locations

CA (2)