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

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ClinicalTrials.gov Identifier: NCT02272504
Recruitment Status : Recruiting
First Posted : October 23, 2014
Last Update Posted : April 27, 2016
Sponsor:
Information provided by (Responsible Party):
Wako Life Sciences

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%.

Condition or disease
Cirrhosis Chronic Liver Diseases

Detailed Description:
This study is a prospective randomized controlled trial (RCT) comparing surveillance for hepatocellular carcinoma with ultrasound alone versus ultrasound and standard biomarkers. The study will be conducted initially at UHN (TGH and TWH). One arm will undergo surveillance for hepatocellular carcinoma using ultrasound (US) alone and the other will undergo HCC surveillance with US plus biomarkers (BM). The biomarkers to be used will be AFP, AFP-L3 and DCP). Subjects will undergo surveillance at 6 monthly intervals for a minimum of 2 years and up to 4 years. The endpoints will be the comparative effectiveness, defined as sensitivity and specificity of detection of HCC. The comparisons of sensitivity, specificity, and other parameters with respect to tumor characteristics will be made among US alone, biomarkers alone, and combined use of US and biomarkers. The target population is individuals who have liver cirrhosis and no HCC detectable at enrollment into the study. The factors contributing to the cause of the cirrhosis will be recorded but will not play a role into subject eligibility for the study

Study Type : Observational
Estimated Enrollment : 2500 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: A Randomized Controlled Trial to Determine the Role of Biomarkers in Surveillance for Hepatocellular Carcinoma (HCC)
Study Start Date : August 2014
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine


Group/Cohort
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.



Primary Outcome Measures :
  1. Biomarker assays exceeding threshold [ Time Frame: Every 6 months until HCC is detected or up to 4 years ]
    Biomarker assay levels that exceed threshold will trigger diagnostic imaging for HCC. Ultrasound imaging indicating a suspicious nodule may also trigger diagnostic imaging.


Secondary Outcome Measures :
  1. Surveillance until HCC development and detection [ Time Frame: Up to 4 years ]
    When the total number of HCC cases as diagnosed by CT/MRI have been observed. Approximately 300 cases in total half (150) the cases from each group


Biospecimen Retention:   Samples Without DNA
Frozen Serum samples will be retained


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

  • Patient who is able and willing to comply with study procedures, and signed and dated informed consent is obtained.

    • Patients with a clinical suspicion of cirrhosis based on the investigator's evaluation with cirrhosis confirmed by one of the following: (see below for definition of cirrhosis). Etiology of cirrhosis will not be considered in determining inclusion in the study.
    • 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

Exclusion Criteria:

  • • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02272504


Contacts
Contact: Morris Sherman, MD 416 340 4756 Dr.Morris.Sherman@uhn.ca
Contact: Jordan Feld, MD 416 603 6230 Jordan.Feld@uhn.ca

Locations
Canada, Ontario
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Morris Sherman, MD    416 340 4756    Dr.Morris.Sherman@uhn.ca   
Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Jordan Feld, MD    416 603 6230    Jordan.Feld@uhn.ca   
Sponsors and Collaborators
Wako Life Sciences
Investigators
Principal Investigator: Morris Sherman, MD Toronto General Hospital

Responsible Party: Wako Life Sciences
ClinicalTrials.gov Identifier: NCT02272504     History of Changes
Other Study ID Numbers: WLS 13-6926
First Posted: October 23, 2014    Key Record Dates
Last Update Posted: April 27, 2016
Last Verified: April 2016

Keywords provided by Wako Life Sciences:
HCC
AFP
AFP-L3
DCP
Surveillance
biomarkers

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases