CirrhosisPhase 1/2NCT02273362

Erlotinib Hydrochloride in Preventing Liver Cancer in Patients With Cirrhosis of the Liver

A Phase 1/2 study testing Erlotinib, Erlotinib Hydrochloride and Laboratory Biomarker Analysis in people with Cirrhosis and Hepatocellular Carcinoma, run by National Cancer Institute (NCI) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Cirrhosis, Hepatocellular Carcinoma
What is being tested?: Erlotinib, Erlotinib Hydrochloride and Laboratory Biomarker Analysis
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 6 sitesUnited States
Study dates: 24 Nov 2014to 10 Mar 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

PRE-REGISTRATION INCLUSION:
Individuals with a clinical diagnosis fibrosis or cirrhosis of the liver (no more than Child-Pugh classification A; Child-Pugh-Turcotte score of 6 or less) who have:
An indication for surgical liver resection, OR
A clinical liver biopsy (with research tissue specimens available for analysis) =< 3 months prior to pre-registration
Willingness to discontinue smoking during the study two weeks prior to beginning the study and willingness to not smoke while taking study medication
Not pregnant or breast feeding. Note: The effects of erlotinib (Tarceva) on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.

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Willingness to use adequate contraception to avoid pregnancy or impregnation until 2 weeks after discontinuing study agent
Willingness to provide mandatory blood specimens
Able to undergo:
Percutaneous or transjugular biopsy of cirrhotic liver at least 7 days prior to liver resection (surgical cohort), OR
A biopsy of the cirrhotic liver (non-surgical cohort)
Willingness to authorize collection of tissue from surgically-resected liver or clinical liver biopsy for analyses
Ability to understand and the willingness to sign a written informed consent document
REGISTRATION INCLUSION:
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
International normalized ratio (INR) =< 1.5
Platelets >= 50 B/L (10^9/L)
Total bilirubin =< 3 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional ULN
Creatinine =< 1.5 x institutional ULN
Non-surgical cohort only: positive phospho-EGFR assessment (>= 100 stained pixels) from tissue obtained from previous clinical liver biopsy
Pre-intervention biopsy sample collected

Who cannot join

PRE-REGISTRATION EXCLUSION:
Any prior treatment with erlotinib or other agent whose primary mechanism of action is known to inhibit EGFR
Participants with a known diagnosis of human immunodeficiency virus (HIV); Note: an HIV screening test does not have to be performed to evaluate this criterion
Participants who regularly (>= 2 times per week) use drugs that alter the pH of the gastrointestinal (GI) tract, such as proton pump inhibitors (PPI) and antacids; exceptions: individuals who use prescription PPIs and have approval from their primary health care provider to discontinue for the duration of clinical trial participation may be enrolled; an alternate drug to control gastroesophageal reflux disease (GERD)/peptic ulcer disease (PUD) symptoms will be suggested
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
Use of potent CYP3A4 inhibitors, such as ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice

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Use of CYP3A4 inducers such as rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's wort
History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib (Tarceva)
Participants who cannot have their warfarin, Lovenox, Plavix, or other comparable medications held for percutaneous or transjugular liver biopsy and surgery if so indicated
Non-surgical cohort only: pathology report from clinical liver biopsy (=< 3 months prior to pre-registration) demonstrates no histologic abnormalities associated with chronic hepatitis, steatohepatitis, fibrosis, or cirrhosis
REGISTRATION EXCLUSION:
Receiving any other investigational agents =< 6 months prior to registration
Surgical cohort (cohort A only): percutaneous or transjugular biopsy incomplete or not performed

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Case Western Reserve University
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Mount Sinai Hospital
New York, New York, 10029
Mayo Clinic in Rochester
Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Pilot Study of EGFR Inhibition With Erlotinib in Cirrhosis to Inhibit Fibrogenesis and Prevent Hepatocellular Carcinoma

This pilot phase I/II trial studies the best dose of erlotinib hydrochloride and to see how well it works in preventing liver cancer in patients with scarring (cirrhosis) of the liver. Erlotinib hydrochloride may help to inhibit the development of fibrous tissue and prevent liver cancer from forming in patients with cirrhosis of the liver.

Read the detailed description

PRIMARY OBJECTIVES:

Determine the safe and minimum effective dose (MED) of daily erlotinib (erlotinib hydrochloride) that inhibits epidermal growth factor receptor (EGFR) signaling in the target organ (liver) as assessed by phosphorylated (phospho)-EGFR staining.

SECONDARY OBJECTIVES:

Determine the relationship between erlotinib dose-schedule and side effects in participants with cirrhosis.

TRANSLATIONAL OBJECTIVES:

Determine the relationship between erlotinib dose-schedule and immuno-histochemical staining pattern of phospho-ERK, proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), and alpha smooth muscle actin (alphaSMA) in the liver.

II. Determine the relationship between erlotinib dose-schedule and gene expression signature associated with prognosis in cirrhosis participants following hepatocellular carcinoma (HCC) resection.

III. Determine the relationship between erlotinib dose-schedule and viral load in participants with hepatitis C virus (HCV) positive (+).

IV. Determine the relationship between erlotinib dose-schedule and erlotinib plasma level on day of liver resection.

OUTLINE: This is a phase I, dose-escalation/de-escalation study followed by a phase II study.

Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for 7 days (depending on the date of surgery, treatment range may be 5-14 days).

Conditions: Cirrhosis, Hepatocellular Carcinoma
Being tested: Erlotinib, Erlotinib Hydrochloride, Laboratory Biomarker Analysis, Quality-of-Life Assessment
Medical subject headings: Fibrosis, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ErlotinibDrug
Given PO
Erlotinib HydrochlorideDrug
Also called Cp-358,774, OSI-774, Tarceva
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies

Study groups in NCT02273362
Study group	Role	What they receive
Prevention (erlotinib hydrochloride)	Experimental	Patients receive erlotinib hydrochloride PO QD for 7 days (depending on the date of surgery, treatment range may be 5-14 days). Receives: Drug: Erlotinib; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

Response (at Least a 50% Reduction in Liver Phospho-EGFR Staining)
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.
Measured: Up to day 7

Secondary outcomes (1)

Adverse Event Profile
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.
Measured: Up to day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Nov 201410 Mar 2022

First posted24 Oct 2014 (estimated)
Study start24 Nov 2014
Primary completion11 Feb 2020
Study completion10 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for CirrhosisStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02273362
Sponsor's protocol ID: NCI-2014-02170
Other IDs: NCI-2014-02170, HHSN261201200042I, N01-CN-2012-00042, MAY2013-02-02, MAY2013-02-02, N01CN00042, P30CA015083
Status last verified: Feb 2024
First submitted: 22 Oct 2014
Last updated: 26 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Tanabe KK, Zahrieh D, Strand CA, Hoshida Y, Flotte TJ, Della'Zanna G, Umar A, Chavin KD, Cleary S, Kubota N, Llovet JM, Patel T, Siegel C, Limburg PJ. Epidermal Growth Factor Receptor Inhibition With Erlotinib in Liver: Dose De-Escalation Pilot Trial as an Initial Step in a Chemoprevention Strategy. Gastro Hep Adv. 2024 Jan 29;3(3):426-439. doi: 10.1016/j.gastha.2024.01.009. eCollection 2024.
PubMed 39131140

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 26 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study of EGFR Inhibition With Erlotinib in Cirrhosis to Inhibit Fibrogenesis and Prevent Hepatocellular Carcinoma
ClinicalTrials.gov ID: NCT02273362
Acronym / sponsor ID: NCI-2014-02170
Conditions: Cirrhosis, Hepatocellular Carcinoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 24 Nov 2014 (actual)
Primary completion: 11 Feb 2020 (actual)
Study completion: 10 Mar 2022 (actual)
First posted: 24 Oct 2014 (estimated)
Results: Posted 25 Feb 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

Determine the safe and minimum effective dose (MED) of daily erlotinib (erlotinib hydrochloride) that inhibits epidermal growth factor receptor (EGFR) signaling in the target organ (liver) as assessed by phosphorylated (phospho)-EGFR staining.

SECONDARY OBJECTIVES:

Determine the relationship between erlotinib dose-schedule and side effects in participants with cirrhosis.

TRANSLATIONAL OBJECTIVES:

Determine the relationship between erlotinib dose-schedule and immuno-histochemical staining pattern of phospho-ERK, proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), and alpha smooth muscle actin (alphaSMA) in the liver.

II. Determine the relationship between erlotinib dose-schedule and gene expression signature associated with prognosis in cirrhosis participants following hepatocellular carcinoma (HCC) resection.

III. Determine the relationship between erlotinib dose-schedule and viral load in participants with hepatitis C virus (HCV) positive (+).

IV. Determine the relationship between erlotinib dose-schedule and erlotinib plasma level on day of liver resection.

OUTLINE: This is a phase I, dose-escalation/de-escalation study followed by a phase II study.

Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for 7 days (depending on the date of surgery, treatment range may be 5-14 days).

Study design

Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Prevention (erlotinib hydrochloride)	Experimental	Drug: Erlotinib, Drug: Erlotinib Hydrochloride, Other: Laboratory Biomarker Analysis, Other: Quality-of-Life AssessmentPatients receive erlotinib hydrochloride PO QD for 7 days (depending on the date of surgery, treatment range may be 5-14 days).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

PRE-REGISTRATION INCLUSION:
Individuals with a clinical diagnosis fibrosis or cirrhosis of the liver (no more than Child-Pugh classification A; Child-Pugh-Turcotte score of 6 or less) who have:
Willingness to discontinue smoking during the study two weeks prior to beginning the study and willingness to not smoke while taking study medication
Not pregnant or breast feeding. Note: The effects of erlotinib (Tarceva) on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
Willingness to use adequate contraception to avoid pregnancy or impregnation until 2 weeks after discontinuing study agent

Key exclusion criteria (13 listed)

PRE-REGISTRATION EXCLUSION:
Any prior treatment with erlotinib or other agent whose primary mechanism of action is known to inhibit EGFR
Participants with a known diagnosis of human immunodeficiency virus (HIV); Note: an HIV screening test does not have to be performed to evaluate this criterion
Participants who regularly (>= 2 times per week) use drugs that alter the pH of the gastrointestinal (GI) tract, such as proton pump inhibitors (PPI) and antacids; exceptions: individuals who use prescription PPIs and have approval from their primary health care provider to discontinue for the duration of clinical trial participation may be enrolled; an alternate drug to control gastroesophageal reflux disease (GERD)/peptic ulcer disease (PUD) symptoms will be suggested
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ErlotinibGiven PO	Drug	Prevention (erlotinib hydrochloride)
Erlotinib HydrochlorideAlso: Cp-358,774, OSI-774, TarcevaGiven PO	Drug	Prevention (erlotinib hydrochloride)
Laboratory Biomarker AnalysisCorrelative studies	Other	Prevention (erlotinib hydrochloride)
Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies	Other	Prevention (erlotinib hydrochloride)

Primary outcome

Response (at Least a 50% Reduction in Liver Phospho-EGFR Staining)
Time frame: Up to day 7
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.

1 secondary outcome

Adverse Event Profile
Time frame: Up to day 7

Results and safety

Results posted to the registry on 25 Feb 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)	5	5
Dose Level -1 (50 mg Erlotinib Daily)	6	6
Dose Level -2 (25 mg Erlotinib Daily)	14	14

Primary outcome: Response (at Least a 50% Reduction in Liver Phospho-EGFR Staining)

Time frame: Up to day 7. Count of participants. Unit: Participants

Measure	Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily) n = 3	Dose Level -1 (50 mg Erlotinib Daily) n = 5	Dose Level -2 (25 mg Erlotinib Daily) n = 10
Value	3	3	6

Population analysed: 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.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 7 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Level 0 ( 75 mg Erlotinib Hydrochloride Daily)	0 of 5 (0%)	2 of 5 (40%)	0 of 5
Dose Level -1 (50 mg Erlotinib Daily)	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Dose Level -2 (25 mg Erlotinib Daily)	1 of 14 (7.1%)	7 of 14 (50%)	0 of 14

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39131140Tanabe KK, Zahrieh D, Strand CA, Hoshida Y, Flotte TJ, Della'Zanna G, Umar A, Chavin KD, Cleary S, Kubota N, Llovet JM, Patel T, Siegel C, Limburg PJ. Epidermal Growth Factor Receptor Inhibition With Erlotinib in Liver: Dose De-Escalation Pilot Trial as an Initial Step in a Chemoprevention Strategy. Gastro Hep Adv. 2024 Jan 29;3(3):426-439. doi: 10.1016/j.gastha.2024.01.009. eCollection 2024.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kenneth K Tanabe principal investigator

Mayo Clinic

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response (at Least a 50% Reduction in Liver Phospho-EGFR Staining) (time frame: Up to day 7). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02273362, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2024.