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.
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. TRANSLATIONAL 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 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 Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
25
Mayo Clinic in Florida
Jacksonville, Florida, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Mount Sinai Hospital
New York, New York, United States
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.
Time frame: Up to day 7
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.
Time frame: Up to day 7
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Ancillary studies
Case Western Reserve University
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States