Erlotinib for Hepatocellular Carcinoma Chemoprevention (ECHO-B)

Phase II Clinical Trial of Low-dose Erlotinib for Hepatocellular Carcinoma Chemoprevention

This phase II randomized placebo-controlled trial studies low-dose erlotinib treatment to assess its efficacy and safety to prevent development of hepatocellular carcinoma in patients with advanced liver fibrosis or cirrhosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Cirrhosis, Liver; Advanced Liver Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: erlotinib hydrochloride

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yujin Hoshida, MD, PhD; Phone Number: 214-648-3111; Email: Yujin.Hoshida@UTSouthwestern.edu
• Study Contact Backup: Name: Lisa Quirk, MS, MPH; Phone Number: 214-648-3111; Email: Lisa.Quirk@UTSouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
      • Contact: Yujin Hoshida; Phone Number: 2146486137; Email: yujin.hoshida@utsouthwestern.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults (≥ 18 years-old)
• Clinically and/or histologically diagnosed advanced liver fibrosis or cirrhosis
• No active hepatic decompensation
• No prior history of HCC
• FIB-4 index > 3.25
• PLSec score ≥ 3
• Adequate hematologic, hepatic, and renal function, Karnofsky performance status score ≥70
• Both sexes and all racial/ethnic groups will be considered

Exclusion Criteria:

• Prior treatment with epidermal growth factor receptor (EGFR) inhibitors
• Uncontrolled intercurrent, use of CYP3A4 modulators
• Erlotinib treatment <4 weeks or <80% of planned regimen at the end of week 4
• HCC development during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: Erlotinib treatment	Drug: erlotinib hydrochloride; Oral administration of erlotinib 50mg (two 25mg capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modulation of serum protein signature associated with hepatocellular carcinoma (HCC) risk	The relationship between the treatment and modulation of a serum protein signature associated with HCC risk (PLSec) will be assessed. PLSec-based HCC risk level (i.e., PLSec score) will be compared between baseline and at the end of treatment, and magnitude of the modulation will be measured as delta-PLSec and compared between the treatment groups by t-test and Wilcoxon rank-sum test.	Baseline, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall adverse event profile for erlotinib hydrochloride	Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. The maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number and severity of adverse events will be tabulated and summarized across all grades. Grade 3+ adverse events will be similarly described and summarized separately. Overall toxicity incidence, as well as toxicity profiles will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.	Baseline, 24 weeks
Change in quality of life (QOL)	QOL will be measured by using Chronic Liver Disease Questionnaire (CLDQ), and compared between baseline and end of the treatment. Frequency distributions, graphical techniques and other descriptive measures will be used to summarize the results. Paired t-test will be used to assess change of the measurements.	Baseline, 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular tissue transcriptome signature associated with HCC risk	When optional liver biopsy tissues are obtained, the relationship between the treatment and modulation of a gene expression signature associated with HCC risk will be assessed. Expression levels of the signature genes will be compared between baseline and at the end of treatment, and magnitude of the modulation will be measured by Kolmogorov-Smirnov statistic-based Combined Enrichment Score (CES) and tested by t-test and Wilcoxon rank-sum test.	Baseline, 24 weeks
Changes in phospho-ERK levels in the liver	When optional liver biopsy tissues are obtained, the relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using analysis of variance (ANOVA) or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests.	Baseline, 24 weeks
Changes in PCNA levels in the liver	When optional liver biopsy tissues are obtained, the relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests.	Baseline, 24 weeks
Changes in EGF levels in the liver	When optional liver biopsy tissues are obtained, the relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests.	Baseline, 24 weeks
Changes in alphaSMA levels in the liver	When optional liver biopsy tissues are obtained, the relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests.	Baseline, 24 weeks
Changes in GSTp levels in the liver	When optional liver biopsy tissues are obtained, the relationship between dose-level and staining of biomarkers in the liver will be assessed. The baseline biomarker expression levels across all the dose levels using ANOVA or the nonparametric equivalent will be compared. The changes in these biomarker values will be assessed using the Wilcoxon signed-rank test and compare these changes across dose levels using ANOVA. Graphical methods will be used to assess the differences in these biomarker values across dose levels. All categorical variables will be analyzed using chi-square or Fisher's exact tests.	Baseline, 24 weeks
Liver stiffness measurement by transient elastography	The change in liver stiffness measurement (LSM) by transient elastography will be evaluated by comparing baseline and at the end of the treatment and compared between the treatment groups by t-test and Wilcoxon rank-sum test.	Baseline, 24 weeks
HCC incidence	HCC incidence after completing the planned treatment will be recorded via standard-care semi-annual HCC screening with ultrasound and AFP. The association of the treatment and HCC incidence will be assessed by Kaplan-Meier method, log-rank test, and Cox regression. Correlation with the primary endpoint will also be assessed. The semi-annual HCC screening will be continued indefinitely and the correlation analysis will be continued.	through study completion, an average of 3 year

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Yujin Hoshida, UT Southwestern; Principal Investigator: Amit Singal, MD, MS, UT Southwestern

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: November 17, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; chemoprevention
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Fibrosis; Pathological Conditions, Signs and Symptoms; Carcinoma, Hepatocellular; Liver Cirrhosis; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines; Erlotinib Hydrochloride
• Other Study ID Numbers: STU-2019-1515; P50CA295495 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared with other researchers.

Drug and device information, study documents

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