Erlotinib for Hepatocellular Carcinoma Chemoprevention

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04172779

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis, Liver	Drug: Erlotinib Hydrochloride	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2027

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Erlotinib treatment

Drug: Erlotinib Hydrochloride

Oral administration of erlotinib 25mg tablet

Outcome Measures

Primary Outcome Measures

Modulation of gene expression signatures associated with hepatocellular carcinoma (HCC) risk [Baseline to week 48]
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.

Secondary Outcome Measures

Overall adverse event profile for erlotinib hydrochloride [Baseline to week 48]
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.
Change in quality of life (QOL) [Baseline to week 48]
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.

Other Outcome Measures

Changes in phospho-ERK levels in the liver [Baseline to week 48]
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.
Changes in PCNA levels in the liver [Baseline to week 48]
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.
Changes in EGF levels in the liver [Baseline to week 48]
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.
Changes in alphaSMA levels in the liver [Baseline to week 48]
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.
Changes in GSTp levels in the liver [Baseline to week 48]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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