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Erlotinib for Hepatocellular Carcinoma Chemoprevention

Primary Purpose

Cirrhosis, Liver

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Erlotinib Hydrochloride
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cirrhosis, Liver focused on measuring hepatocellular carcinoma, chemoprevention

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Erlotinib treatment

    Arm Description

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.

    Full Information

    First Posted
    November 17, 2019
    Last Updated
    August 29, 2023
    Sponsor
    University of Texas Southwestern Medical Center
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04172779
    Brief Title
    Erlotinib for Hepatocellular Carcinoma Chemoprevention
    Official Title
    Phase IIa Single-arm Clinical Trial of Hepatocellular Carcinoma Chemoprevention With Low-dose Erlotinib in Patients With Liver Cirrhosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 2024 (Anticipated)
    Primary Completion Date
    June 2029 (Anticipated)
    Study Completion Date
    June 2029 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Texas Southwestern Medical Center
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cirrhosis, Liver
    Keywords
    hepatocellular carcinoma, chemoprevention

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    30 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Erlotinib treatment
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Erlotinib Hydrochloride
    Intervention Description
    Oral administration of erlotinib 25mg tablet
    Primary Outcome Measure Information:
    Title
    Modulation of gene expression signatures associated with hepatocellular carcinoma (HCC) risk
    Description
    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.
    Time Frame
    Baseline to week 48
    Secondary Outcome Measure Information:
    Title
    Overall adverse event profile for erlotinib hydrochloride
    Description
    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.
    Time Frame
    Baseline to week 48
    Title
    Change in quality of life (QOL)
    Description
    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.
    Time Frame
    Baseline to week 48
    Other Pre-specified Outcome Measures:
    Title
    Changes in phospho-ERK levels in the liver
    Description
    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.
    Time Frame
    Baseline to week 48
    Title
    Changes in PCNA levels in the liver
    Description
    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.
    Time Frame
    Baseline to week 48
    Title
    Changes in EGF levels in the liver
    Description
    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.
    Time Frame
    Baseline to week 48
    Title
    Changes in alphaSMA levels in the liver
    Description
    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.
    Time Frame
    Baseline to week 48
    Title
    Changes in GSTp levels in the liver
    Description
    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.
    Time Frame
    Baseline to week 48

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yujin Hoshida, MD, PhD
    Phone
    214-648-3111
    Email
    Yujin.Hoshida@UTSouthwestern.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Amit Singal, MD, MS
    Phone
    214-648-3111
    Email
    Amit.Singal@UTSouthwestern.edu

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    No IPD will be shared with other researchers.

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    Erlotinib for Hepatocellular Carcinoma Chemoprevention

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