Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 3 months prior.

4. Cirrhosis based on the following:

1. For viral hepatitis, 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.

2. For non-viral hepatitis, 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 the following:

1. For viral hepatitis, 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.

2. For non-viral hepatitis, 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 3 months prior based on one of the following:

1. Negative multiphase CT scan or MRI 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 at 6-month 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. 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.

4. Prior treatment of tumor.

5. 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.

2. Uncontrolled ascites.

3. Uncontrolled encephalopathy.

4. 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).

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

Study Design

Phase
Study Type
Observational
Observational Model
Case-Control
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
Cases Male and female adult patients with early-stage hepatocellular carcinoma against a background of liver cirrhosis.
Controls Male and female adult patients with liver cirrhosis at risk for hepatocellular carcinoma.

Recruiting Locations

University of Maryland, Baltimore
Baltimore, Maryland 21201
Contact:
Kirti Shetty, MD

More Details

Status
Recruiting
Sponsor
Glycotest, Inc.

Study Contact

Charles S Swindell, PhD
484-431-3483
charles@glycotest.com

Detailed 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 and capped at 30% of total Chronic Hepatitis C cases and controls. Cases and controls will be matched based on age, sex and etiology.

Number of Subjects:

Maximum of 438 cases and 438 controls;

- 200 cases and 200 controls (training set)

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

Study Duration:

12 months (1 year 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.