Clinical Trials /

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

NCT02273362

Description:

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.

Related Conditions:
  • Liver Cirrhosis
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Erlotinib Hydrochloride in Preventing Liver Cancer in Patients With Cirrhosis of the Liver Undergoing Surgery
  • Official Title: Pilot Study of EGFR Inhibition With Erlotinib in Cirrhosis to Inhibit Fibrogenesis and Prevent Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2014-02170
  • SECONDARY ID: NCI-2014-02170
  • SECONDARY ID: HHSN261201200042I
  • SECONDARY ID: N01-CN-2012-00042
  • SECONDARY ID: MAY2013-02-02
  • SECONDARY ID: MAY2013-02-02
  • SECONDARY ID: N01CN00042
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02273362

Conditions

  • Cirrhosis
  • Fibrosis
  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
Erlotinib HydrochlorideCp-358,774, OSI-774, TarcevaPrevention (erlotinib hydrochloride)

Purpose

This pilot clinical 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 undergoing surgery. Erlotinib hydrochloride may help to inhibit the development of fibrous tissue and prevent liver cancer from forming in patients with cirrhosis of the liver.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

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

      TERTIARY OBJECTIVES:

      I. 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 dose-escalation 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).
    

Trial Arms

NameTypeDescriptionInterventions
Prevention (erlotinib hydrochloride)ExperimentalPatients receive erlotinib hydrochloride PO QD for 7 days (depending on the date of surgery, treatment range may be 5-14 days).
  • Erlotinib Hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  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; 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

          -  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 × institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 ×
             institutional ULN

          -  Creatinine =< 1.5 × 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

        Exclusion Criteria:

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MED of erlotinib hydrochloride that inhibits EGFR signaling in the target organ (liver) as assessed by phospho-EGFR staining
Time Frame:Up to day 7
Safety Issue:
Description:The MED that achieves at least a 40% response rate, where a response is defined as an evaluable participant that achieves at least a 50% reduction in liver phospho-EGFR staining, defined as the percentage of positive pixels, from baseline after a 7-day intervention period with daily erlotinib hydrochloride will be evaluated.

Secondary Outcome Measures

Measure:Overall adverse event profile for erlotinib hydrochloride graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4
Time Frame:Up to the day of liver resection
Safety Issue:
Description: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.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

April 7, 2017