Erlotinib for Hepatocellular Carcinoma Chemoprevention

Study Overview
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Brief Summary
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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.

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

Conditions
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Cirrhosis, Liver

Intervention / Treatment
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* Drug: Erlotinib Hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib treatment<br> | Drug: Erlotinib Hydrochloride<br>* Oral administration of erlotinib 25mg tablet<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, chemoprevention