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Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients (PRIUS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Young-Suk Lim, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01446666
First received: September 17, 2011
Last updated: November 23, 2013
Last verified: November 2013
  Purpose

Current practice guidelines recommend surveillance for hepatocellular carcinoma (HCC) in liver cirrhosis patients with ultrasonography (USG) every 6 months. However, with the advancement of cirrhosis, the sensitivity of USG decreases, while the risk for HCC increases. Gadoxetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) has been demonstrated to be of clinical value for diagnosis of HCC with the detection sensitivity of 90-95%, which is significantly higher than USG. The hypothesis to be proved by this study is as follows; Primovist-MRI should show significantly higher sensitivity compared to USG for the detection of early stage HCC when both of these imaging modalities are used with the interval of 6 months in patients with cirrhosis at high risk of developing HCC.


Condition
Cirrhosis of Liver

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Intra-individual Cohort Study to Compare Gadoxetic Acid (Primovist®)-Enhanced Magnetic Resonance Image and Ultrasonography for the Surveillance of Early Stage Hepatocellular Carcinoma in Patients at High-risk

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • The detection sensitivity of early stage HCC [ Time Frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening) ] [ Designated as safety issue: No ]
    • The number of definite HCC nodules of early stage detected by a given modality divided by the total number of definite HCC nodules of early stage detected by any of 2 modalities plus interval cancers
    • Early stage (stage A or 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC <5 cm or <=3 lesions each <3 cm in diameter, without gross vascular invasion or extrahepatic metastasis.


Secondary Outcome Measures:
  • The detection sensitivity of patients with early stage HCC [ Time Frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening) ] [ Designated as safety issue: No ]
    • The number of patients with early stage HCC detected by a given modality divided by the total number of patients with early stage HCC detected by any of 2 modalities plus interval cancers.
    • Early stage (stage A or 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC <5 cm or <=3 lesions each <3 cm in diameter, without gross vascular invasion or extrahepatic metastasis.

  • The detection sensitivity of very early stage HCC [ Time Frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening) ] [ Designated as safety issue: No ]
    • The number of definite HCC nodules of very early stage detected by a given modality divided by the total number of definite HCC nodules of very early stage detected by any of 2 modalities plus interval cancers.
    • Very early stage (stage 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC <2 cm without gross vascular invasion or extrahepatic metastasis.

  • The detection sensitivity of all stage HCC [ Time Frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening) ] [ Designated as safety issue: No ]
    - The number of definite HCC nodules detected by a given modality divided by the total number of definite HCC nodules detected by any of 2 modalities plus interval cancers.

  • The detection specificity for all stage HCC [ Time Frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening) ] [ Designated as safety issue: No ]
    Number of true-negative results divided by the sum of true negative results and false-positive results (ie, examinations leading to a negative biopsy or CT scan)

  • The cost-effectiveness for each surveillance tests [ Time Frame: during the 1.5-year study period (from the date of first screening to 6 months following the last screening) ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Buffy coat and serum


Estimated Enrollment: 423
Study Start Date: November 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
HCC high-risk group

Patients with liver cirrhosis with the 1-year risk of HCC of 5% or higher

; High Risk Index (>=2.33)

Risk Index = 1.65 (if the prothrombin activity is <=75%) + 1.41 (if the age is 50 years or older) + 0.92 (if the platelet count is <=100x10(3)/mm3) + 0.74 (if the presence of anti-hepatitis C virus [HCV] or hepatitis B surface antigen [HBsAg] is positive).


Detailed Description:

Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer-related deaths worldwide. Cirrhosis, particularly when related to viral hepatitis, is the most notable risk factor for HCC and is found in nearly 80-90% of cases.

The stage of disease at the time of diagnosis largely determines the effectiveness of treatment. The treatment of advanced HCC continues to be primarily palliative, with curative options only available for early HCC. Unfortunately, less than 30% of patients are diagnosed early enough to meet criteria for resection, transplantation, or local ablation.

Surveillance strives to detect HCC at an early stage when it is amenable to curative therapy to reduce mortality. Current practice guidelines recommend surveillance of cirrhotic patients with ultrasonography (USG) every 6 months. However, USG has been reported to have a sensitivity of between 65% and 80% when used as a screening test. However, with the advancement of cirrhosis, the sensitivity of USG decreases, while the risk for HCC increases.

Gadoxetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) of the liver has been demonstrated to be of clinical value for local staging before HCC surgery and for the assessment of patients with inconclusive conventional imaging findings. The detection sensitivity of Primovist-MRI has been known to be as high as 90-95%, which is significantly higher than USG or multiphase computer tomography (CT) scan. MRI does not have radiation exposure, which is a meaningful merit to be used as a surveillance test. However, MRI has never been considered for surveillance or screening of HCC.

Thus, the hypothesis to be proved by this study is as follows; Primovist-MRI should show significantly higher sensitivity compared to USG for the detection of early stage HCC when both of these imaging modalities are used with the interval of 6 months in patients with cirrhosis at high risk of developing HCC. The investigators will also analyze whether the specificity of Primovist-MRI are not compromised by its high sensitivity.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Hospital out-patient clinic

Criteria

Inclusion Criteria:

Patients with liver cirrhosis with the 1 year risk of HCC of 5% or higher meeting all of following criteria;

  1. The evidence of cirrhosis of any etiology within 12 months prior to screening Definition of cirrhosis by any of following methods

    • 1) Histologically by liver biopsy;
    • 2) Non-histologically by evidence of portal hypertension in the presence of chronic liver disease;

      • Evidence of portal hypertension, including any of followings;

        1. The identification of splenomegaly on USG, CT, or MRI examinations with typical features of cirrhosis
        2. The identification of esophageal or gastric varices on endoscopic examination
  2. High Risk Index (>=2.33); Risk Index = 1.65 (if the prothrombin activity is <=75%) + 1.41 (if the age is 50 years or older) + 0.92 (if the platelet count is <=100x10(3)/mm3) + 0.74 (if the presence of anti-hepatitis C virus [HCV] or hepatitis B surface antigen [HBsAg] is positive).
  3. Older than 20 years of age
  4. Absence of previous or current history of HCC
  5. Absence of HCC should be identified by liver USG, dynamic CT, or contrast-enhanced MRI within 6 months prior to screening
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
  7. Patient is able to comply with scheduled visits, evaluation plans, and other study procedures.
  8. Patient is willing to provide written informed consent

Exclusion Criteria:

Presence of any of following criteria;

  1. Active or suspected cancer other than HCC, or a history of malignancy where the risk of recurrence is >20% within 2 years
  2. Significant medical comorbidities in which survival is predicted to be less than 3 years
  3. Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73m2
  4. Precautions for MRI (cardiac pacemaker, ferromagnetic implants, etc.)
  5. Severe claustrophobia that may interfere with protocol compliance.
  6. Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrollment or could interfere with the completing the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01446666

Locations
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 135-837
Sponsors and Collaborators
Asan Medical Center
Bayer
Investigators
Principal Investigator: Young-Suk Lim, MD, PhD Asan Medical Center
  More Information

No publications provided

Responsible Party: Young-Suk Lim, Associate Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01446666     History of Changes
Other Study ID Numbers: AMC2011-0587
Study First Received: September 17, 2011
Last Updated: November 23, 2013
Health Authority: South Korea: Institutional Review Board

Keywords provided by Asan Medical Center:
hepatocellular carcinoma
surveillance
gadoxetic acid
MRI

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Liver Cirrhosis
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Gadolinium ethoxybenzyl DTPA
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2014