NCT01013831终止1 期
A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Change in the ratio of p-EGFR to total EGFR
研究概览
简要总结
This phase I trial studies the side effects and best dose of erlotinib hydrochloride in preventing cancer in patients with precancerous lesions of the lung. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the lowest dose of erlotinib (erlotinib hydrochloride) that will decrease the ratio of phosphorylated to total epidermal growth factor receptor (EGFR) (phosphorylated EGFR [pEGFR]/EGFR) by at least 20% in subjects with premalignant lesions of the lung. This will be accomplished by implementing a dose de-escalation trial of erlotinib (i.e., 75, 50, and 25 or 100 mg by mouth daily for a 3-month period), and determining the pEGFR/EGFR ratio in premalignant lesions of the lung epithelium by immunohistochemistry. Changes in the pEGFR/EGFR ratio will be assessed by comparing the pre-treatment (baseline) ratio to that of the post-treatment (3 month) ratio, measured in paraffin embedded biopsy specimens.
SECONDARY OBJECTIVES:
I. To determine the effect of erlotinib on the following biomarkers of potential biological relevance in paraffin embedded lung biopsies, p-v-akt murine thymoma viral oncogene homolog 1 (Akt), p-mitogen-activated protein kinase 1 (Erk), and marker of proliferation Ki-67 (Ki67).
II. To characterize the toxicity profile of erlotinib in this cohort of subjects.
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
- 40 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of a premalignant lung lesion (metaplasia or dysplasia) on autofluorescent bronchoscopy (AFB) within 1 month
- •Participants must have a >= 10 pack year lifetime smoking history; current and former smokers only are eligible for this trial
- •No contraindications for treatment with erlotinib or additional bronchoscopies
- •Absolute neutrophil count (ANC) of >= 1.5 x 10^9/L
- •Platelet count of >= 100 x 10^9/L
- •Creatinine level of less than 1.5 mg/dL
- •Total bilirubin =< 2.0 mg/dl
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN)
- •Alkaline phosphatase =< 2.5 x ULN
- •Must meet Eastern Cooperative Oncology Group (ECOG) performance status criteria of 0-1
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) throughout the duration of the study and for 1 month following cessation of study drug; females must begin adequate contraception immediately following screening pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; if she is pregnant, she will be immediately withdrawn from the study
- •Ability to understand and the willingness to sign a written institutional review board (IRB) approved informed consent document
排除标准
- •Subjects with life-threatening medical conditions that would preclude the treatment intervention and bronchoscopy, including, but not limited to, unstable pulmonary function, acute cardiac failure, which is unstable despite medication use; uncontrolled hypertension; uncontrolled diabetes mellitus; unstable coronary artery disease; acute or chronic liver disease, ongoing or active infection; or psychiatric illness/social situations that would limit compliance with study requirements
- •Participants with evidence of an active cancer or carcinoma in situ, are not eligible
- •Participants currently taking medications that induce or inhibit the cytochrome P450, family 3, subfamily A, polypeptide 4-7 (CYP3A4-7) enzymes
- •Participants may not be receiving any other investigational agents within 3 months
- •Participants taking warfarin
- •History of allergic reactions attributed to erlotinib, a known hypersensitivity to erlotinib, or agents with a similar chemical or biological composition to erlotinib
- •Women who are pregnant or lactating are excluded from the study because based on the proposed mechanism of tyrosine kinase inhibition of erlotinib; erlotinib should be assumed to cause fetal harm when administered to a pregnant woman; there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with erlotinib
- •History of interstitial lung disease (ILD)
研究组 & 干预措施
Prevention (erlotinib hydrochloride)
Experimental
Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity.
干预措施: Erlotinib Hydrochloride (Drug)
Prevention (erlotinib hydrochloride)
Experimental
Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Prevention (erlotinib hydrochloride)
Experimental
Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Change in the ratio of p-EGFR to total EGFR
时间窗: Baseline up to 90 days
次要结局
- Change in the expression of p-Akt(Baseline up to 90 days)
- Change in the expression of Ki67(Baseline up to 90 days)
- Change in the expression of p-Erk(Baseline up to 90 days)
- Incidence of toxicities, graded according to Common Toxicity Criteria, version 3.0(Up to 30 days)
研究者
研究点 (4)
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