Erlotinib Hydrochloride in Preventing Cancer in Patients With Precancerous Lesions of the Lung
A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung
調査の概要
詳細な説明
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.
III. To analyze and model erlotinib's pharmacokinetic/pharmacodynamic (PK/PD) profile. Serial blood samples will be drawn at the beginning and at the end of erlotinib treatment, and pharmacokinetic parameters will be determined. The status of EGFR genotype (and that of others genes linked to erlotinib PK/PD) clinical toxicity, and dose will be examined as possible other influential covariates by comparing them to experimentally measured PK profiles, and PD profiles (in particular, the pEGFR/EGFR ratio). The goal of these studies will be to determine the optimal biologic concentration (OBC) of Erlotinib that is associated with the lowest toxicity and highest effect, for a given subject's pharmacogenomic profile.
OUTLINE:
Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for 90 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Illinois
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Chicago、Illinois、アメリカ、60611
- Northwestern University
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Chicago、Illinois、アメリカ、60637
- University of Chicago Comprehensive Cancer Center
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Massachusetts
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Boston、Massachusetts、アメリカ、02118
- Boston University School of Medicine
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New York
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Buffalo、New York、アメリカ、14263
- Roswell Park Cancer Institute
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Prevention (erlotinib hydrochloride)
Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity.
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与えられたPO
他の名前：
相関研究
相関研究
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
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Change in the ratio of p-EGFR to total EGFR
時間枠：Baseline up to 90 days
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Baseline up to 90 days
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in the expression of p-Akt
時間枠：Baseline up to 90 days
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Analyzed using an analysis-of-variance (ANOVA) on the change from baseline expression level with a factor for dose (75, 50, 25 or 100).
All tests will be two-sided and tested at level alpha=0.05.
If the overall comparison is significant, pairwise comparisons will be done using straight Bonferroni adjustments.
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Baseline up to 90 days
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Change in the expression of p-Erk
時間枠：Baseline up to 90 days
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Analyzed using an ANOVA on the change from baseline expression level with a factor for dose (75, 50, 25 or 100).
All tests will be two-sided and tested at level alpha=0.05.
If the overall comparison is significant, pairwise comparisons will be done using straight Bonferroni adjustments.
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Baseline up to 90 days
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Change in the expression of Ki67
時間枠：Baseline up to 90 days
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Analyzed using an ANOVA on the change from baseline expression level with a factor for dose (75, 50, 25 or 100).
All tests will be two-sided and tested at level alpha=0.05.
If the overall comparison is significant, pairwise comparisons will be done using straight Bonferroni adjustments.
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Baseline up to 90 days
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Incidence of toxicities, graded according to Common Toxicity Criteria, version 3.0
時間枠：Up to 30 days
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Up to 30 days
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その他の成果指標
結果測定 |
時間枠 |
|---|---|
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PK/PD parameters
時間枠：Up to 90 days
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Up to 90 days
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Pharmacogenomic profile
時間枠：Up to 90 days
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Up to 90 days
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協力者と研究者
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- NCI-2013-00750 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- P30CA060553 (米国 NIH グラント/契約)
- N01CN35157 (米国 NIH グラント/契約)
- RPCI-I-121507
- NU-NWU08-11-01
- STU00012618
- NCI 08-11-01 (その他の識別子：Northwestern University)
- NWU08-11-01 (その他の識別子：DCP)
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