ALTUS: Performance of a Multi- Target Hepatocellular Carcinoma (HCC) Test in Subjects With Increased Risk

The primary objective is to assess overall sensitivity and specificity of Oncoguard™ Liver for hepatocellular cancer (HCC) detection in a surveillance population.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatitis B; Hepatocellular Carcinoma; Cirrhosis; Liver Cancer; Hepatocellular Cancer
• Intervention / Treatment: Device: Study CT/MRI Imaging; Device: Standard of Care CT/MRI Imaging; Diagnostic test: Oncoguard™ Liver Test

Detailed Description

The study will include participants aged 18 years and older who are at increased risk for HCC, including individuals with liver cirrhosis or non-cirrhotic individuals with chronic hepatitis B infection.

• Study Type: Observational
• Enrollment (Actual): 2990

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Arizona Health Research
    • Sun City, Arizona, United States, 85251
      • Arizona Digestive Health - Sun City
  • California
    • Bakersfield, California, United States, 93301
      • Franco Felizarta, MD
    • Escondido, California, United States, 92025
      • Gastroenterology & Liver Institute
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Mission Hills, California, United States, 91345
      • Providence Facey Medical Foundation
    • Murrieta, California, United States, 92563
      • United Medical Doctors
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • Palo Alto, California, United States, 94303
      • VA Palo Alto Healthcare System
    • Pasadena, California, United States, 91107
      • California Liver Research Institute
    • Poway, California, United States, 92064
      • Cadena Care Institute
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials
    • San Diego, California, United States, 92105
      • Research & Education, Inc
    • San Jose, California, United States, 95128
      • San Jose Gastroenterology
  • Colorado
    • Littleton, Colorado, United States, 80120
      • Rocky Mountain Gastroenterology
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20422
      • Washington DC VA Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Hepatology Research at CTRB
    • Jacksonville, Florida, United States, 32256
      • ENCORE Borland Groover Clinical Research
    • Jacksonville, Florida, United States, 32209
      • University of Florida - College of Medicine
    • Lakewood, Florida, United States, 34211
      • Florida Research Institute
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33125
      • Miami VA Healthcare System
    • Miami Lakes, Florida, United States, 33014
      • San Marcus Research Clinic
    • Tampa Bay, Florida, United States, 33606
      • Tampa General Hospital
  • Illinois
    • Downers Grove, Illinois, United States, 60515
      • Digestive Health Services
    • Glenview, Illinois, United States, 60026
      • Illinois Gastroenterology Group
    • Gurnee, Illinois, United States, 60031
      • GI Alliance of Illinois - Gurnee
    • Lake Barrington, Illinois, United States, 60010
      • Gastroenterology and Internal Medicine Specialists
    • Oak Lawn, Illinois, United States, 60463
      • Avicenna Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46237
      • Indianapolis Gastroenterology Research Foundation
    • Indianapolis, Indiana, United States, 46201
      • NAVREF - Indiana Institute for Medical Research (IIMC)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center, LLC
  • Maryland
    • Nottingham, Maryland, United States, 21236
      • Patient First Clinical Trials
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Rochester
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research LLC (STAR)
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center
    • St Louis, Missouri, United States, 63104
      • St. Louis University
  • New York
    • Brooklyn, New York, United States, 11209
      • Brooklyn VA Medical Center
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai
    • New York, New York, United States, 10279
      • Manhattan Clinical Research, LLC
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Digestive Health Partners
    • Durham, North Carolina, United States, 27710
      • Duke University Health Systems
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • VA North East Ohio Health Care System
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Great Lakes Medical Research - Susquehanna Research Group
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Xiaoli MA MD
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Corporal Michael J. Crescenz VA Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Wilkes-Barre VA Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • University Gastroenterology West River
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H Johnson VAMC
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • El Paso, Texas, United States, 79936
      • Texas Gastro Clinic
    • Houston, Texas, United States, 77030
      • Baylor - Saint Luke's Medical Center
    • Lubbock, Texas, United States, 79410
      • Lubbock Digestive Disease Associates
    • San Marcos, Texas, United States, 78666
      • Texas Digestive Disease Consultants - San Marcos
    • Webster, Texas, United States, 77598
      • Tranquil Clinical Research
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • UVA Gastroenterology
    • Manassas, Virginia, United States, 20110
      • Gastroenterology Associates, PC
    • Norfolk, Virginia, United States, 23502
      • Digestive & Liver Disease Specialists
    • Richmond, Virginia, United States, 23226
      • Bon Secours Liver Institute of Richmond
    • Richmond, Virginia, United States, 23249
      • Richmond VA Medical Center
  • Washington
    • Bellevue, Washington, United States, 98056
      • Washington Gastroenterology - Bellevue
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Spokane, Washington, United States, 99202
      • Velocity Clinical Research
    • Tacoma, Washington, United States, 98405
      • Washington Gastroenterology - Tacoma
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • UW Digestive Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects 18 years of age and older who are at an increased risk for HCC and for whom HCC surveillance is appropriate, including subjects with cirrhosis and non-cirrhotic subjects with Hepatitis B.

Description

Inclusion Criteria:

1. Be 18 years of age or older.
2. Understand the study procedures, be able to provide written informed consent to participate in the study, and have authorization for release of data, including personal health data and images, to the study Investigator, Sponsor, and regulatory authorities.

3. Present for surveillance imaging due to increased risk for HCC, including either:

   1. Diagnosis of cirrhosis based on at least one of the following:

      • Histology from a liver biopsy.
      • Ultrasound, CT, or MRI showing a cirrhotic liver combined with portal hypertension (as evidenced by the presence of intra-abdominal varices, or recanalized umbilical vein, or ascites or splenomegaly or thrombocytopenia [defined as Platelet count < 150,000]). The imaging results must have been obtained within 5 years of study enrollment.
      • Liver stiffness ≥4.71 kilopascal (kPa) by Magnetic Resonance (MR) elastography or ≥12.1 kPa by vibration controlled transient elastography.
      • Presence of varices on endoscopy or imaging and presence of a chronic liver disease. Endoscopy or imaging results must have been obtained within 5 years of study enrollment.

      OR

   2. Non-cirrhotic subjects with chronic Hepatitis B Virus (HBV) infection (Hepatitis B surface antigen present for >6 months)

Exclusion Criteria:

1. Known cancer diagnosis (including active malignancy) within the past 5 years except for nonmelanoma skin cancer.
2. Chemotherapy and/or radiation therapy within 5 years prior to study enrollment.
3. Known Child-Pugh class C liver function at the time of enrollment, except for those on the waiting list for transplant.
4. Solid liver nodule >1 cm by ultrasound or elevated Alpha-fetoprotein (AFP) (>100 ng/mL) in 12 months preceding the qualifying surveillance imaging visit without subsequent documentation of HCC negative or LIRADS 1 (Liver Imaging Reporting and Data System) by diagnostic CT/MRI.
5. Females known to be pregnant at the time of enrollment.

6. Illness that the Investigator believes poses a significant risk of mortality during the study period, including but not limited to

   1. Congestive heart failure with ejection fraction <50%
   2. Chronic lung disease requiring supplemental oxygen.
   3. History of recent stroke.
7. Sustained virologic response (SVR) for Hepatitis C Virus (HCV) (undetectable HCV RNA 12 to 24 weeks after completion of antiviral therapy) for >10 years prior to enrollment.

8. Not able to have IV contrast for CT or MRI due to

   1. Allergy to IV contrast and unwilling or unable to receive IV contrast after pre-medication.
   2. Estimated glomerular filtration rate <35 mL/min and not on hemodialysis.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ultrasound Surveillance Group; Subjects will undergo standard of care ultrasound surveillance imaging. Subjects with positive ultrasound are anticipated to have standard of care imaging follow-up with CT or MRI as well as other procedures as needed. Subjects with negative ultrasound will be sent for a study CT/MRI.	Device: Study CT/MRI Imaging; Subjects with negative ultrasound will be sent for a study CT/MRI.; Device: Standard of Care CT/MRI Imaging; Subjects with positive ultrasound are anticipated to have standard of care imaging follow-up as well as other procedures as needed.; Diagnostic test: Oncoguard™ Liver Test; Subjects will have a blood sample collected for the Oncoguard™ Liver Test.
CT/MRI Surveillance Group; Subjects will undergo standard of care CT/MRI surveillance imaging.	Device: Standard of Care CT/MRI Imaging; Subjects with positive ultrasound are anticipated to have standard of care imaging follow-up as well as other procedures as needed.; Diagnostic test: Oncoguard™ Liver Test; Subjects will have a blood sample collected for the Oncoguard™ Liver Test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To demonstrate that Oncoguard™ Liver early-stage HCC sensitivity is non-inferior to that of ultrasound within a 5% margin	A maximum of 30 days from study or standard-of-care CT or MRI exam.
To demonstrate that Oncoguard™ Liver HCC specificity exceeds 82%	A maximum of 30 days from study or standard-of-care CT or MRI exam.

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine a point estimate and 95% confidence interval for Oncoguard™ Liver overall HCC sensitivity	A maximum of 30 days from study or standard-of-care CT or MRI exam.

Other Outcome Measures

Outcome Measure	Time Frame
Overall and early-stage sensitivity as well as specificity of ultrasound	Treatment and outcomes data will be collected for up to 3 years post-enrollment.

Collaborators and Investigators

• Sponsor: Exact Sciences Corporation
• Investigators: Principal Investigator: Binu John, Miami VA Healthcare System

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Actual): September 12, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 21, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Ultrasound; Blood Sample Collection; CT/MRI; Combined Hepatocellular and Cholangiocarcinoma; HCC Surveillance
• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Neoplasms by Site; Neoplasms; Infections; Virus Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Communicable Diseases; DNA Virus Infections; Carcinoma; Hepadnaviridae Infections; Hepatitis; Pathological Conditions, Signs and Symptoms; Carcinoma, Hepatocellular; Liver Neoplasms; Fibrosis; Hepatitis B
• Other Study ID Numbers: 2021-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in publications of the study will be shared after deidentification. This may include test, tables, figures, and appendices. The study protocol, statistical analysis plan (when applicable), informed consent form (when applicable), and the clinical study report (when applicable) will also be shared
• IPD Sharing Time Frame: Data will be available from 2 years and ending 4 years after publication.
• IPD Sharing Access Criteria: Proposals for access to data should be directed to clinicaltrials@exactsciences.com. To gain access, data requestors will need to provide a methodologically sound proposal and sign a data access agreement. Researchers are required to obtain necessary IRB/IEC approvals or waivers as applicable to conduct research.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No