Erlotinib Hydrochloride in Preventing Cancer in Patients With Precancerous Lesions of the Lung
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01013831|
Recruitment Status : Terminated
First Posted : November 16, 2009
Last Update Posted : February 18, 2015
|Condition or disease||Intervention/treatment||Phase|
|Dysplasia Metaplasia Pulmonary Precancerous Condition||Drug: Erlotinib Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung|
|Study Start Date :||October 2009|
|Actual Primary Completion Date :||February 2012|
|Actual Study Completion Date :||June 2013|
Experimental: Prevention (erlotinib hydrochloride)
Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity.
Drug: Erlotinib Hydrochloride
Other Name: Cp-358,774
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Other Name: pharmacological studies
- Change in the ratio of p-EGFR to total EGFR [ Time Frame: Baseline up to 90 days ]
- Change in the expression of p-Akt [ Time Frame: Baseline up to 90 days ]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 [ Time Frame: Baseline up to 90 days ]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 [ Time Frame: Baseline up to 90 days ]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.
- Incidence of toxicities, graded according to Common Toxicity Criteria, version 3.0 [ Time Frame: Up to 30 days ]
- PK/PD parameters [ Time Frame: Up to 90 days ]
- Pharmacogenomic profile [ Time Frame: Up to 90 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01013831
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Boston University School of Medicine|
|Boston, Massachusetts, United States, 02118|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Seema Khan||Northwestern University|