Erlotinib for Hepatocellular Carcinoma Chemoprevention

Cirrhosis, Liver Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04172779
• Other study ID #: STU-2019-1515
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: June 2029

Study information

• Verified date: August 2023
• Source: University of Texas Southwestern Medical Center
• Contact: Yujin Hoshida, MD, PhD
• Phone: 214-648-3111
• Email: Yujin.Hoshida[@]UTSouthwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: June 2029
• Est. primary completion date: June 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Erlotinib Hydrochloride
Oral administration of erlotinib 25mg tablet

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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