## Protocol Section
### Identification Module
**NCT ID:** 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

#### Organization Study ID Info
**ID:** STU-2019-1515
#### Organization
**Class:** OTHER
**Full Name:** University of Texas Southwestern Medical Center
### Status Module
#### Completion Date
**Date:** 2029-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-09-01

**Type:** ACTUAL

**Last Update Submit Date:** 2023-08-29

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2029-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07

**Type:** ESTIMATED

**Status Verified Date:** 2023-08

#### Study First Post Date
**Date:** 2019-11-21
**Type:** ACTUAL
**Study First Submit Date:** 2019-11-17
**Study First Submit QC Date:** 2019-11-19
### Sponsor Collaborators Module

#### Collaborators

**Class:** NIH

**Name:** National Cancer Institute (NCI)

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Texas Southwestern Medical Center

#### Responsible Party

**Investigator Affiliation:** University of Texas Southwestern Medical Center

**Investigator Full Name:** Yujin Hoshida, MD, PhD

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Cirrhosis, Liver

**Keywords:**

- hepatocellular carcinoma

- chemoprevention

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Erlotinib Hydrochloride

**Label:** Erlotinib treatment

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Erlotinib treatment

**Description:** Oral administration of erlotinib 25mg tablet

**Name:** Erlotinib Hydrochloride

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**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.

**Measure:** Changes in phospho-ERK levels in the liver

**Time Frame:** Baseline to week 48

**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.

**Measure:** Changes in PCNA levels in the liver

**Time Frame:** Baseline to week 48

**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.

**Measure:** Changes in EGF levels in the liver

**Time Frame:** Baseline to week 48

**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.

**Measure:** Changes in alphaSMA levels in the liver

**Time Frame:** Baseline to week 48

**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.

**Measure:** Changes in GSTp levels in the liver

**Time Frame:** Baseline to week 48

#### Primary Outcomes

**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.

**Measure:** Modulation of gene expression signatures associated with hepatocellular carcinoma (HCC) risk

**Time Frame:** Baseline to week 48

#### Secondary Outcomes

**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.

**Measure:** Overall adverse event profile for erlotinib hydrochloride

**Time Frame:** Baseline to week 48

**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.

**Measure:** Change in quality of life (QOL)

**Time Frame:** Baseline to week 48

### Eligibility Module

**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

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Yujin.Hoshida@UTSouthwestern.edu

**Name:** Yujin Hoshida, MD, PhD

**Phone:** 214-648-3111

**Role:** CONTACT

**Contact 2:**

**Email:** Amit.Singal@UTSouthwestern.edu

**Name:** Amit Singal, MD, MS

**Phone:** 214-648-3111

**Role:** CONTACT

### IPD Sharing Statement Module

**Description:** No IPD will be shared with other researchers.

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000008113

- Term: Liver Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000008107

- Term: Liver Diseases

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: HIGH

- As Found: Carcinoma

- ID: M9613

- Name: Carcinoma, Hepatocellular

- Relevance: HIGH

- As Found: Hepatocellular Carcinoma

- ID: M11103

- Name: Liver Cirrhosis

- Relevance: HIGH

- As Found: Cirrhosis, Liver

- ID: M8485

- Name: Fibrosis

- Relevance: HIGH

- As Found: Cirrhosis

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M11113

- Name: Liver Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11107

- Name: Liver Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002277

- Term: Carcinoma

- ID: D000006528

- Term: Carcinoma, Hepatocellular

- ID: D000008103

- Term: Liver Cirrhosis

- ID: D000005355

- Term: Fibrosis

### Intervention Browse Module - Ancestors

- ID: D000092004

- Term: Tyrosine Kinase Inhibitors

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M11110

- Name: Liver Extracts

- Relevance: LOW

- As Found: Unknown

- ID: M398

- Name: Erlotinib Hydrochloride

- Relevance: HIGH

- As Found: On study

- ID: M2889

- Name: Tyrosine Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T22

- Name: Tyrosine

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000069347

- Term: Erlotinib Hydrochloride

### Misc Info Module

- Version Holder: 2024-05-24
