临床试验/NCT02273362

NCT02273362已完成1 期

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

National Cancer Institute (NCI)6 个研究点分布在 1 个国家目标入组 25 人开始时间: 2014年11月24日最近更新: 2024年3月26日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 25
试验地点: 6
主要终点: Response (at Least a 50% Reduction in Liver Phospho-EGFR Staining)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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:

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Prevention
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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

排除标准

•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

研究组 & 干预措施

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).

干预措施: Erlotinib (Drug)

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).

干预措施: Erlotinib Hydrochloride (Drug)

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).

干预措施: Laboratory Biomarker Analysis (Other)

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).

干预措施: Quality-of-Life Assessment (Other)

结局指标

主要结局

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

时间窗: 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.

次要结局

Adverse Event Profile(Up to day 7)

研究者

发起方

National Cancer Institute (NCI)

申办方类型

Nih

责任方

Sponsor

研究点 (6)

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