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

NCT02273362 | Completed Phase 1 Results DMC

• 6 other identifiers: NCI-2014-02170HHSN261201200042IN01-CN-2012-00042MAY2013-02-02N01CN00042P30CA015083
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Cirrhosis; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to day 7

Secondary Outcomes (1)

• Adverse Event Profile

  Up to day 7

Other Outcomes (7)

• Changes in Phospho-ERK Levels in the Liver

  Baseline to day 7

• Changes in PCNA Levels in the Liver

  Baseline to day 7

• Changes in EGF Levels in the Liver

  Baseline to day 7

Study Arms (1)

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).

Drug: Erlotinib; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

Interventions

Erlotinib DRUG

Given PO

Prevention (erlotinib hydrochloride)

Erlotinib Hydrochloride DRUG

Given PO

Also known as: Cp-358,774, OSI-774, Tarceva

Prevention (erlotinib hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Prevention (erlotinib hydrochloride)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Prevention (erlotinib hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• International normalized ratio (INR) =\< 1.5
• Platelets \>= 50 B/L (10\^9/L)

You may not qualify if:

• 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
• 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
• Receiving any other investigational agents =\< 6 months prior to registration
• Surgical cohort (cohort A only): percutaneous or transjugular biopsy incomplete or not performed

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• 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.

  PMID: 39131140 DERIVED

MeSH Terms

Conditions

Fibrosis; Carcinoma, Hepatocellular

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Kenneth K. Tanabe, M.D.
• Organization: Mayo Clinic

ktanabe@partners.org

507-284-2511

Study Officials

• Kenneth K Tanabe

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: October 24, 2014
• Study Start: November 24, 2014
• Primary Completion: February 11, 2020
• Study Completion: March 10, 2022
• Last Updated: March 26, 2024
• Results First Posted: February 25, 2022

Record last verified: 2024-02

Locations

US (6)