Trial Title:
National Liver Cancer Screening Trial
NCT ID:
NCT06084234
Condition:
Carcinoma, Hepatocellular
Liver Cancer
Liver Cirrhosis
Hepatitis B
Conditions: Official terms:
Hepatitis B
Liver Neoplasms
Carcinoma, Hepatocellular
Liver Cirrhosis
Conditions: Keywords:
Hepatocellular carcinoma surveillance
GALAD
Alpha Fetoprotein
Study type:
Interventional
Study phase:
Phase 4
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
This is a randomized open-label study comparing US ± AFP vs. GALAD-based surveillance
every 6 (± 3-month window) months starting at randomization.
Primary purpose:
Screening
Masking:
None (Open Label)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
GALAD
Description:
GALAD is a 3 biomarker panel incorporating AFP, AFP-L3% and DCP (all FDA approved), with
patient age and sex.
Arm group label:
Arm B: Semi-annual surveillance using GALAD
Intervention type:
Diagnostic Test
Intervention name:
Liver Ultrasound with or without AFP
Description:
This intervention consists of current standard of care ultrasound based surveillance with
or without alpha-fetoprotein measurement.
Arm group label:
Arm A: Semi-annual surveillance using liver ultrasound +/- alpha-fetoprotein
Summary:
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.
Detailed description:
The TRACER phase IV biomarker study is a randomized trial comparing ultrasound-based
screening versus a biomarker-based strategy in patients with cirrhosis. In brief, 5500
patients with cirrhosis from any etiology would be randomized in a 1:1 fashion to Arm A
offering semi-annual ultrasound +/- AFP-based screening or Arm B offering semi-annual
biomarker-based screening. Randomization will be stratified by site, Child Pugh class (A
vs. B), liver disease etiology (viral, non-viral, and non-cirrhotic HBV infection) and
sex. Patients will be recruited from 15 sites (mix of tertiary care and large community
health systems) over a 3-year period, and reduction in the proportion of late-stage HCC,
will be assessed at the end of Year 5.5. If the results are promising, study team will
continue extended follow-up and compare the incidence of late-stage HCC between the two
arms at Year 8 and reduction in HCC mortality during long term follow up.
Study team will include adult patients, age ≥ 18 years, with Child Pugh class A or B
cirrhosis of any etiology or non-cirrhotic chronic hepatitis B virus infection with
PAGE-B score >9. Study team will exclude patients post liver transplantation, patients
with Child Pugh C cirrhosis, patients with significant comorbidity and limited life
expectancy, and those with history of other malignancy, except non-melanoma skin cancer
or indolent tumors, within 3 years prior to enrollment given lack of screening
recommendations in those patient populations. Study team will also exclude patients with
suspicious liver masses at baseline as well as those with a solid lesion ≥1 cm on
ultrasound or AFP ≥20 ng/mL without diagnostic evaluation to exclude HCC. Study team will
also exclude patients in whom the provider plans to follow the patient with CT or
MRI-based surveillance. GALAD is not recommended in patients with pregnancy or active
warfarin use given known impact on biomarker performance, so these patients will be
excluded.
At enrollment, study team will record patient demographics and clinical characteristics
using a combination of electronic medical records and patient questionnaires. Patients
will then be offered semi-annual surveillance as defined by their study arm: ultrasound
and AFP for patients in Arm A and the biomarker, GALAD, for patients in Arm B. Repeat
surveillance tests will be offered every six months (per assigned arm) for patients with
normal surveillance results. Diagnostic evaluation with multi-phasic CT or
contrast-enhanced MRI will be recommended for any patients with abnormal screening
results. Patients with normal diagnostic testing (i.e., false positive result) will be
recommended to return to their assigned surveillance arm. Standardized criteria from the
AASLD and LI-RADS will be used to define incident HCC. Study team will use a set of
validated surveys (e.g., Psychological Consequences Questionnaire, Decision Regret scale,
FACIT-COST) to measure secondary outcomes of interest including psychological and
financial harms.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patient must meet all of the following inclusion criteria:
1. Adult patients ages 18-85 with cirrhosis from any etiology or with chronic hepatitis
B with a PAGE-B score greater than 9 within 12 months of enrollment
2. Patient is eligible for HCC surveillance according to treating physician or by the
site investigator
3. Able to provide informed consent
4. Life expectancy >6 months (after consent) as determined by the treating provider or
site investigator
Exclusion Criteria:
Patient will be excluded for any of the following exclusion criteria:
1. Child Pugh C cirrhosis
2. History or clinical symptoms of hepatocellular carcinoma or cholangiocarcinoma
3. History of solid nodule on baseline ultrasound (i.e., lesion 1cm or greater) within
9 months prior to consent without subsequent diagnostic CT/MRI demonstrating benign
nature)
4. AFP >20 ng/mL within 6 months prior to consent, in the absence of a
contrast-enhanced CT or MRI within 6 months of AFP (before or after) level
demonstrating lack of suspicious liver lesions
5. Newly diagnosed LR-3 greater than or equal to 1 cm within 6 months prior to consent
6. History of LR-4, LR-5, or LR-M on multi-phase CT or contrast-enhanced MRI within 6
months prior to consent
7. Presence of another active cancer besides non-melanomatous skin cancer or indolent
cancer under active surveillance (e.g., prostate cancer or renal cell carcinoma)
within the 2 years prior to consent
8. Patient's provider is planning to use MRI- or CT- based surveillance moving forward
9. History of a transjugular intrahepatic portosystemic shunt (TIPS)
10. History of Fontan associated liver disease or cardiac cirrhosis
11. History of solid organ transplantation
12. Actively listed for liver transplantation
13. Diagnosis of alcohol-associated hepatitis within 3 months prior to consent
14. Documented current or continued signs and symptoms of acute Wilson disease (acute
liver failure, acute neurological deficits, hemolysis)
15. In patients with primary sclerosing cholangitis (PSC): Current active cholangitis
within 90 days prior to consent
16. Known or documented habitual non-adherence to previous research studies or medical
procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent
or samples)
17. In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60
days prior to consent
18. Known pregnancy at consent
19. Active warfarin use
Gender:
All
Minimum age:
18 Years
Maximum age:
85 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Southern California
Address:
City:
Los Angeles
Zip:
90089
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kali Zhou, MD
Investigator:
Last name:
Kali Zhou, MD
Email:
Principal Investigator
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94117
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rae Davis
Email:
rayshawnda.davis@ucsf.edu
Investigator:
Last name:
Neil Mehta, MD
Email:
Principal Investigator
Facility:
Name:
Indiana University
Address:
City:
Indianapolis
Zip:
46202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sherri Cummins
Email:
shcummin@iu.edu
Investigator:
Last name:
Naga Chalasani, MD
Email:
Principal Investigator
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Contact:
Last name:
Megan Michta
Email:
MMICHTA@mgh.harvard.edu
Investigator:
Last name:
Irun Bhan, MD
Email:
Principal Investigator
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shay Robison
Email:
roshay@med.umich.edu
Investigator:
Last name:
Neehar Parikh, MD, MS
Email:
Principal Investigator
Facility:
Name:
Henry Ford Health System
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jessica Peruski
Email:
jperusk1@hfhs.org
Investigator:
Last name:
Reena Salgia, MD
Email:
Principal Investigator
Facility:
Name:
The Feinstein Institutes, Northwell Health, Inc.
Address:
City:
Manhasset
Zip:
11030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dibnain Nanda
Email:
dnanda1@northwell.edu
Investigator:
Last name:
Sanjaya Satapathy, MBBS, MS
Email:
Principal Investigator
Facility:
Name:
University of Pennsylvania
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Grace Kim
Email:
gracekim.lee@pennmedicine.upenn.edu
Investigator:
Last name:
Jorge Marrero, MD,MS
Email:
Principal Investigator
Facility:
Name:
UT Southwestern Medical Center and Parkland Hospital
Address:
City:
Dallas
Zip:
75390
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sneha Deodhar, MS
Phone:
214-645-1378
Email:
TRACER@UTSouthwestern.edu
Investigator:
Last name:
Amit Singal, MD, MS
Email:
Principal Investigator
Facility:
Name:
Baylor College of Medicine
Address:
City:
Houston
Zip:
77021
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sara Fares
Contact backup:
Email:
Sara.Fares@bcm.edu
Investigator:
Last name:
Fasiha Kanwal, MD, MSHS
Email:
Principal Investigator
Start date:
December 26, 2023
Completion date:
December 31, 2034
Lead sponsor:
Agency:
University of Texas Southwestern Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
University of Pennsylvania
Agency class:
Other
Collaborator:
Agency:
University of Michigan
Agency class:
Other
Collaborator:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Baylor College of Medicine
Agency class:
Other
Collaborator:
Agency:
Fred Hutchinson Cancer Center
Agency class:
Other
Source:
University of Texas Southwestern Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06084234
