Case-Control Study of the Glycotest™ HCC Panel vs AFP for the Detection of Early-stage Hepatocellular Carcinoma

Carcinoma, Hepatocellular Clinical Trial

Official title:

Case-Control Study of the Glycotest™ HCC Panel vs AFP for the Detection of Early-stage Hepatocellular Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03878550
• Other study ID #: G-1001
• Status: Active, not recruiting
• Start date: May 22, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: Glycotest, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Clinical guidelines (AASLD) recommend the use of abdominal ultrasound (US) for surveillance testing for the early detection of Hepatocellular Carcinoma (HCC). The serum protein biomarker alpha-fetoprotein (AFP) is commonly used to augment US but its use alone is not recommended by clinical guidelines. Despite evidence that HCC surveillance improves early detection and reduces mortality from HCC, current HCC surveillance tests lack sensitivity, leaving a significant proportion of patients to present with late-stage disease. The Glycotest HCC Panel has shown better sensitivity than AFP, which is ineffective for the detection of early-stage HCC. This clinical study seeks to validate the Glycotest HCC Panel using a large multicenter cohort of cases and controls that includes patients diagnosed with early-stage HCC against a background of cirrhosis and cirrhotic patients without HCC (at risk) undergoing an established surveillance protocol.

Description:

Study Rationale:

This study is designed to compare the ability of the Glycotest HCC Panel with that of AFP to differentiate between patients with early-stage Hepatocellular Carcinoma (HCC) against a background of cirrhosis from cirrhotic patients without HCC (at risk).

Primary Objective:

The primary objective of this study is to determine whether the Glycotest HCC Panel outperforms AFP in terms of area under the receiver operating characteristic curve (AUROC) for the differentiation of patients with early-stage HCC from those without HCC in the at-risk population.

Secondary Objective:

The secondary objective of this study is to determine whether the Glycotest HCC Panel outperforms AFP in terms of clinical sensitivity (as estimated using the 90% specificity estimate as the decision threshold) for the detection of patients with early-stage HCC.

Study Design:

This is a phase 2, multicenter, laboratory-blinded, case-control study of the Glycotest HCC Panel vs AFP for the discrimination of patients with early-stage HCC from those at risk. Case and control samples will be obtained from multiple institutions using prospective collection. The study will consist of a screening/baseline visit for all patients; controls initially assessed by abdominal US will also undergo a 6-month follow-up visit to confirm absence of HCC at enrollment. Assays will be performed by Glycotest with analysts blinded to clinical data.

Population:

The study population will comprise male and female adult patients with early-stage HCC against a background of cirrhosis (cases) as well as at-risk cirrhotic patients (controls). Enrollment of the aggregate of HCC cases with single lesions ≥ 3 cm and with multiple lesions will be capped at 50% of total cases. Enrollment of Chronic Hepatitis C cases and controls with sustained virologic response (SVR) to therapy will be matched. Cases and controls will be matched based on age, sex and etiology.

Number of Subjects:

Maximum of 388 cases and 378 controls;

• 150 cases and 140 controls (training set)

• Maximum of 238 cases and 238 controls (validation set)

Study Duration:

30 months ( approximately 24 months accrual + 6 month follow up)

Study Phases Patients potentially eligible for the study population will undergo informed consent prior to screening/baseline visits.

Screening Once consented, a subject's demographics, medical record, laboratory data, and imaging will be reviewed. Patients are considered eligible for enrollment once they meet all study enrollment criteria.

Enrollment Screening data will be re-reviewed if necessary and recorded. Serum from blood samples (5 mL) will be obtained for measurement of Glycotest HCC Panel score (which includes AFP).

Follow up Medical record review/imaging at 6 months from enrollment for control patients originally assessed using abdominal US.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 766
• Est. completion date: December 31, 2024
• Est. primary completion date: August 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Cases

1. Males and females ages 18 years or older.

2. Treatment-naïve HCC as defined by LI-RADS (Liver Imaging Reporting and Data System) LR-5 or OPTN (Organ Procurement and Transplantation Network) 5 CT or MRI criteria (all lesions must exhibit arterial phase hyper-enhancement), or histologic evidence.

3. Early-stage HCC defined by single lesion = 5 cm or = 3 lesions = 3 cm determined at enrollment or within 100 days prior without vascular invasion.

4. Cirrhosis based on serum biomarkers (FibroSure®/FibroTest > 0.74, APRI (AST to Platelet Ratio Index) > 2, or FIB-4 (Fibrosis-4) > 3.25), histology, imaging, elastography, or clinical evidence of portal hypertension in the setting of known chronic liver disease.

5. Child-Pugh score A-B8.

6. Subject must be able to understand and provide informed consent.

Controls

1. Males and females ages 18 or older.

2. Cirrhosis based on serum biomarkers (FibroSure®/FibroTest > 0.74, APRI > 2, or FIB-4 > 3.25), histology, imaging, elastography, or clinical evidence of portal hypertension in the setting of known chronic liver disease.

3. Evidence of the absence of a solid hepatic mass, suspicious for HCC, at enrollment or within 100 days prior based on one of the following:

1. Negative multiphase CT scan or MRI with contrast at screening/baseline visit, OR

2. Negative abdominal US at both screening/baseline visit AND 6-month follow-up visit, OR

3. Negative abdominal US at screening/baseline visit AND negative multiphase CT scan or MRI with contrast at 6-month or earlier follow-up visit.

4. Child-Pugh score A-B8.

5. Subject must be able to understand and provide informed consent.

Exclusion Criteria:

Cases

1. Uncontrolled ascites.

2. Uncontrolled encephalopathy.

3. History of liver transplant.

4. Diagnosis of active malignancy or history of active malignancy within 5 years prior to enrollment, including mixed HCC-CCA (cholangiocarcinoma). If previously diagnosed with malignancy, subject must be in remission for at least 5 years prior to enrollment. Prior history of HCC, including resection of HCC at any time, is excluded.

5. Prior treatment of tumor.

6. Any significant non-liver-related medical condition in which expected survival is less than 1 year.

Controls

1. Imaging evidence of solid hepatic mass, suspicious for HCC, including lesions meeting LI-RADS LR-3 or LR-4, OPTN-3 or OPTN-4, or LI-RADS LR-M criteria.

2. Uncontrolled ascites.

3. History of liver transplantation.

4. Uncontrolled encephalopathy.

5. Diagnosis of active malignancy or history of active malignancy within 5 years prior to enrollment (if previously diagnosed with malignancy, subject must be in remission for at least 5 years prior to enrollment). History of HCC including resection of HCC at any time, is excluded.

6. Any significant non-liver-related medical condition in which expected survival is less than 1 year.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Cirrhosis, Liver
• Liver Cirrhosis

Locations

Country	Name	City	State
Israel	Hebrew University- Hadassah Medical Center	Jerusalem
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Maryland, Baltimore	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Northwestern University	Chicago	Illinois
United States	Baylor Scott & White Research Institute	Dallas	Texas
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Cedars- Sinai Medical Center	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	Miami VA Healthcare System	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	Hospital of the University of Pennsylvania (HUP)	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Kaiser Permanente Northern California	San Francisco	California
United States	University of California- San Francisco	San Francisco	California
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Glycotest, Inc.

Countries where clinical trial is conducted

United States,  Israel, 

References & Publications (1)

Wang M, Sanda M, Comunale MA, Herrera H, Swindell C, Kono Y, Singal AG, Marrero J, Block T, Goldman R, Mehta A. Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC. Cancer Epidemiol Biomarkers Prev. 2017 May;26(5):795-803. doi: 10.1158/1055-9965.EPI-16-0974. Epub 2017 Feb 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUROC	Area under the receiver operating characteristics curve	At enrollment
Secondary	Sensitivity	Clinical sensitivity for the detection of early-stage hepatocellular carcinoma as estimated using the 90% specificity estimate as the decision threshold	At enrollment