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

This is an interventional prevention trial for Cirrhosis Read More

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. 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
• 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

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