Trial Outcomes & Findings for Erlotinib Hydrochloride in Preventing Liver Cancer in Patients With Cirrhosis of the Liver (NCT NCT02273362)
NCT ID: NCT02273362
Last Updated: 2024-03-26
Results Overview
A response is defined as having at least a 50% reduction in liver phospho-EGFR staining (50% reduction in the percentage of positive pixels).\> \> For each dose level, we report the number of participants achieving a response (at least 50% reduction in liver phospho-EGFR staining). \> \> The Minimum effective dose (MED) is defined as the dose which at least a 40% of patients report a response.
COMPLETED
PHASE1/PHASE2
25 participants
Up to day 7
2024-03-26
Participant Flow
Participant milestones
| Measure |
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)
Patients receive 75 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -1 (50 mg Erlotinib Daily)
Patients receive 50 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -2 (25 mg Erlotinib Daily)
Patients receive 25 mg erlotinib hydrochloride PO QD for 7 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
5
|
6
|
14
|
|
Overall Study
COMPLETED
|
5
|
6
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Erlotinib Hydrochloride in Preventing Liver Cancer in Patients With Cirrhosis of the Liver
Baseline characteristics by cohort
| Measure |
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)
n=5 Participants
Patients receive 75 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -1 (50 mg Erlotinib Daily)
n=6 Participants
Patients receive 50 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -2 (25 mg Erlotinib Daily)
n=14 Participants
Patients receive 25 mg erlotinib hydrochloride PO QD for 7 days.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
61 years
n=99 Participants
|
58.5 years
n=107 Participants
|
66 years
n=206 Participants
|
64 years
n=7 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
17 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
18 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
20 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=99 Participants
|
6 participants
n=107 Participants
|
14 participants
n=206 Participants
|
25 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Up to day 7Population: In Dose Level 0, 1 participant terminated intervention early due to physician decision and 1 participant lost pre-intervention tissue specimens. 1 participant in dose level -1 terminated intervention early due to adverse event. In Dose Level -2, 3 participants did not have additional pre-intervention tissue specimens available beyond eligibility and 1 participant was not evaluable for phospho-EGFR staining at post-intervention due to no benign liver tissue.
A response is defined as having at least a 50% reduction in liver phospho-EGFR staining (50% reduction in the percentage of positive pixels).\> \> For each dose level, we report the number of participants achieving a response (at least 50% reduction in liver phospho-EGFR staining). \> \> The Minimum effective dose (MED) is defined as the dose which at least a 40% of patients report a response.
Outcome measures
| Measure |
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)
n=3 Participants
Patients receive 75 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -1 (50 mg Erlotinib Daily)
n=5 Participants
Patients receive 50 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -2 (25 mg Erlotinib Daily)
n=10 Participants
Patients receive 25 mg erlotinib hydrochloride PO QD for 7 days.
|
|---|---|---|---|
|
Response (at Least a 50% Reduction in Liver Phospho-EGFR Staining)
|
3 Participants
|
3 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to day 7Population: All patients that began protocol treatment are included in this analysis.
Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4. For this endpoint, we are reporting the number of participants with Grade 3 or higher as their worst reported adverse event.
Outcome measures
| Measure |
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)
n=5 Participants
Patients receive 75 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -1 (50 mg Erlotinib Daily)
n=6 Participants
Patients receive 50 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -2 (25 mg Erlotinib Daily)
n=14 Participants
Patients receive 25 mg erlotinib hydrochloride PO QD for 7 days.
|
|---|---|---|---|
|
Adverse Event Profile
|
0 Participants
|
1 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to day 7The 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to day 7The 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to day 7The 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to day 7The 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to day 7The relationship between dose and modulation of a gene expression signature associated with prognosis in cirrhosis 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 7 daysWhether erlotinib hydrochloride is associated with a measurable reduction in viral load in participants with HCV+ will be determined. 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day of liver resectionThe relationship between erlotinib hydrochloride dose-schedule and erlotinib hydrochloride plasma level on the day of liver resection will be determined.
Outcome measures
Outcome data not reported
Adverse Events
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)
Dose Level -1 (50 mg Erlotinib Daily)
Dose Level -2 (25 mg Erlotinib Daily)
Serious adverse events
| Measure |
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)
n=5 participants at risk
Patients receive 75 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -1 (50 mg Erlotinib Daily)
n=6 participants at risk
Patients receive 50 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -2 (25 mg Erlotinib Daily)
n=14 participants at risk
Patients receive 25 mg erlotinib hydrochloride PO QD for 7 days.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
Other adverse events
| Measure |
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)
n=5 participants at risk
Patients receive 75 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -1 (50 mg Erlotinib Daily)
n=6 participants at risk
Patients receive 50 mg erlotinib hydrochloride PO QD for 7 days.
|
Dose Level -2 (25 mg Erlotinib Daily)
n=14 participants at risk
Patients receive 25 mg erlotinib hydrochloride PO QD for 7 days.
|
|---|---|---|---|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Cardiac disorders
Chest pain - cardiac
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 2 • 7 days
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
14.3%
2/14 • Number of events 2 • 7 days
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Oth spec
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
14.3%
2/14 • Number of events 2 • 7 days
|
|
Gastrointestinal disorders
Stomach pain
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
General disorders
Fatigue
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
General disorders
Flu like symptoms
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
Infections and infestations
Infections and infestations - Oth spec
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
Investigations
Blood bilirubin increased
|
20.0%
1/5 • Number of events 1 • 7 days
|
0.00%
0/6 • 7 days
|
0.00%
0/14 • 7 days
|
|
Metabolism and nutrition disorders
Metabolism, nutrition disord - Oth spec
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal, conn tissue - Oth spec
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Nervous system disorders
Headache
|
20.0%
1/5 • Number of events 1 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Renal and urinary disorders
Urinary urgency
|
20.0%
1/5 • Number of events 1 • 7 days
|
0.00%
0/6 • 7 days
|
0.00%
0/14 • 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Sinus pain
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/5 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
0.00%
0/14 • 7 days
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
20.0%
1/5 • Number of events 1 • 7 days
|
16.7%
1/6 • Number of events 1 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
|
Skin and subcutaneous tissue disorders
Skin and subcut tissue disord - Oth spec
|
0.00%
0/5 • 7 days
|
0.00%
0/6 • 7 days
|
7.1%
1/14 • Number of events 1 • 7 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60