Erlotinib for Hepatocellular Carcinoma Chemoprevention

Phase IIa Single-arm Clinical Trial of Hepatocellular Carcinoma Chemoprevention With Low-dose Erlotinib in Patients With Liver Cirrhosis

This phase IIa trial studies long-term low-dose erlotinib hydrochloride treatment to assess its efficacy and safety to prevent development of hepatocellular carcinoma in patients with liver cirrhosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Cirrhosis, Liver
• Intervention / Treatment: Drug: Erlotinib Hydrochloride

• Study Type: Interventional
• Enrollment (Estimated): 30
• 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: Amit Singal, MD, MS; Phone Number: 214-648-3111; Email: Amit.Singal@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 cirrhosis
• No active hepatic decompensation
• No prior history of HCC
• 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
• Failed biopsy
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib treatment	Drug: Erlotinib Hydrochloride; Oral administration of erlotinib 25mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modulation of gene expression signatures associated with hepatocellular carcinoma (HCC) risk	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 for significance by using one-sample t-test.	Baseline to week 48

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 to week 48
Change in quality of life (QOL)	QOL will be measured by using the SF-12v2 health survey questionnaire, 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 to week 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in phospho-ERK levels in the liver	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 to week 48
Changes in PCNA levels in the liver	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 to week 48
Changes in EGF levels in the liver	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 to week 48
Changes in alphaSMA levels in the liver	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 to week 48
Changes in GSTp levels in the liver	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 to week 48

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

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): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; chemoprevention
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Fibrosis; Carcinoma; Carcinoma, Hepatocellular; Liver Cirrhosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: STU-2019-1515

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