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Erlotinib Hydrochloride in Preventing Cancer in Patients With Precancerous Lesions of the Lung

Primary Purpose

Dysplasia, Metaplasia, Pulmonary Precancerous Condition

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Erlotinib Hydrochloride

Laboratory Biomarker Analysis

Pharmacological Study

About this trial

This is an interventional prevention trial for Dysplasia

Eligibility Criteria

40 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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in this study, she should inform her study physician immediately; if she is pregnant, she will be immediately withdrawn from the study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)

Sites / Locations

Northwestern University
University of Chicago Comprehensive Cancer Center
Boston University School of Medicine
Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Prevention (erlotinib hydrochloride)

Arm Description

Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Change in the ratio of p-EGFR to total EGFR

Secondary Outcome Measures

Change in the expression of p-Akt

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.

Change in the expression of p-Erk

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.

Change in the expression of Ki67

Incidence of toxicities, graded according to Common Toxicity Criteria, version 3.0

Full Information

NCT ID

NCT01013831

First Posted

November 13, 2009

Last Updated

February 17, 2015

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01013831

Brief Title

Erlotinib Hydrochloride in Preventing Cancer in Patients With Precancerous Lesions of the Lung

Official Title

A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Terminated

Study Start Date

October 2009 (undefined)

Primary Completion Date

February 2012 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dysplasia, Metaplasia, Pulmonary Precancerous Condition

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Prevention (erlotinib hydrochloride)

Arm Type

Experimental

Arm Description

Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity.

Intervention Type

Drug

Intervention Name(s)

Erlotinib Hydrochloride

Other Intervention Name(s)

Cp-358,774

Intervention Description

Given PO

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

Pharmacological Study

Other Intervention Name(s)

pharmacological studies

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

Change in the ratio of p-EGFR to total EGFR

Time Frame

Baseline up to 90 days

Secondary Outcome Measure Information:

Title

Change in the expression of p-Akt

Description

Time Frame

Baseline up to 90 days

Title

Change in the expression of p-Erk

Description

Time Frame

Baseline up to 90 days

Title

Change in the expression of Ki67

Description

Time Frame

Baseline up to 90 days

Title

Incidence of toxicities, graded according to Common Toxicity Criteria, version 3.0

Time Frame

Up to 30 days

Other Pre-specified Outcome Measures:

Title

PK/PD parameters

Time Frame

Up to 90 days

Title

Pharmacogenomic profile

Time Frame

Up to 90 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Seema Khan

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

University of Chicago Comprehensive Cancer Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Boston University School of Medicine

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

Facility Name

Roswell Park Cancer Institute

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Erlotinib Hydrochloride in Preventing Cancer in Patients With Precancerous Lesions of the Lung

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