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| ID | Type | Description | Link |
|---|---|---|---|
| P50CA295495 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase II randomized placebo-controlled trial studies low-dose erlotinib treatment to assess its efficacy and safety to prevent development of hepatocellular carcinoma in patients with advanced liver fibrosis or cirrhosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Erlotinib treatment | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| erlotinib hydrochloride | Drug | Oral administration of erlotinib 50mg (two 25mg capsules) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Modulation of serum protein signature associated with hepatocellular carcinoma (HCC) risk | The relationship between the treatment and modulation of a serum protein signature associated with HCC risk (PLSec) will be assessed. PLSec-based HCC risk level (i.e., PLSec score) will be compared between baseline and at the end of treatment, and magnitude of the modulation will be measured as delta-PLSec and compared between the treatment groups by t-test and Wilcoxon rank-sum test. | Baseline, 24 weeks |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Molecular tissue transcriptome signature associated with HCC risk | When optional liver biopsy tissues are obtained, 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 by t-test and Wilcoxon rank-sum test. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lisa Quirk, MS, MPH | Contact | 214-648-3111 | Lisa.Quirk@UTSouthwestern.edu | |
| Yujin Hoshida, MD, PhD | Contact | 214-648-3111 | Yujin.Hoshida@UTSouthwestern.edu |
| Name | Affiliation | Role |
|---|---|---|
| Yujin Hoshida | UT Southwestern | Principal Investigator |
| Amit Singal, MD, MS | UT Southwestern | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT Southwestern Medical Center | Dallas | Texas | 75390 | United States |
No IPD will be shared with other researchers.
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| ID | Term |
|---|---|
| D008103 | Liver Cirrhosis |
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D000069347 | Erlotinib Hydrochloride |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Placebo |
|
| Baseline, 24 weeks |
| Change in quality of life (QOL) | QOL will be measured by using Chronic Liver Disease Questionnaire (CLDQ), 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, 24 weeks |
| Baseline, 24 weeks |
| Changes in phospho-ERK levels in the liver | When optional liver biopsy tissues are obtained, 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, 24 weeks |
| Changes in PCNA levels in the liver | When optional liver biopsy tissues are obtained, 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, 24 weeks |
| Changes in EGF levels in the liver | When optional liver biopsy tissues are obtained, 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, 24 weeks |
| Changes in alphaSMA levels in the liver | When optional liver biopsy tissues are obtained, 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, 24 weeks |
| Changes in GSTp levels in the liver | When optional liver biopsy tissues are obtained, 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, 24 weeks |
| Liver stiffness measurement by transient elastography | The change in liver stiffness measurement (LSM) by transient elastography will be evaluated by comparing baseline and at the end of the treatment and compared between the treatment groups by t-test and Wilcoxon rank-sum test. | Baseline, 24 weeks |
| HCC incidence | HCC incidence after completing the planned treatment will be recorded via standard-care semi-annual HCC screening with ultrasound and AFP. The association of the treatment and HCC incidence will be assessed by Kaplan-Meier method, log-rank test, and Cox regression. Correlation with the primary endpoint will also be assessed. The semi-annual HCC screening will be continued indefinitely and the correlation analysis will be continued. | through study completion, an average of 3 year |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |