DysplasiaPhase 1NCT01013831
Erlotinib Hydrochloride in Preventing Cancer in Patients With Precancerous Lesions of the Lung
A Phase 1 study testing Erlotinib Hydrochloride, Laboratory Biomarker Analysis and Pharmacological Study in people with Dysplasia and Metaplasia, run by National Cancer Institute (NCI) at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 79 years
- Conditions the study is for
- Dysplasia, Metaplasia, Pulmonary Precancerous Condition
- What is being tested?
- Erlotinib Hydrochloride, Laboratory Biomarker Analysis and Pharmacological Study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2009to Jun 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Boston University School of Medicine
Boston, Massachusetts, 02118
Roswell Park Cancer Institute
Buffalo, New York, 14263
Northwestern University
Chicago, Illinois, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
About this study
Official title: A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Dysplasia, Metaplasia, Pulmonary Precancerous Condition
- Being tested
- Erlotinib Hydrochloride, Laboratory Biomarker Analysis, Pharmacological Study
- Medical subject headings
- Metaplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erlotinib HydrochlorideDrug
Also called Cp-358,774
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Prevention (erlotinib hydrochloride) | Experimental | Patients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the ratio of p-EGFR to total EGFR
Measured: Baseline up to 90 days
Secondary outcomes (4)
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.
Measured: Baseline up to 90 days
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.
Measured: Baseline up to 90 days
Change in the expression of Ki67
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.
Measured: Baseline up to 90 days
Incidence of toxicities, graded according to Common Toxicity Criteria, version 3.0
Measured: Up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2009 (estimated)
- Study startOct 2009
- Primary completionFeb 2012
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DysplasiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Seema Khan, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01013831
- Sponsor's protocol ID
- NCI-2013-00750
- Other IDs
- NCI-2013-00750, RPCI-I-121507, NU-NWU08-11-01, STU00012618, NCI 08-11-01, NWU08-11-01, P30CA060553, N01CN35157
- Status last verified
- Apr 2014
- First submitted
- 13 Nov 2009
- Last updated
- 18 Feb 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung
- ClinicalTrials.gov ID
- NCT01013831
- Acronym / sponsor ID
- NCI-2013-00750
- Conditions
- Dysplasia, Metaplasia, Pulmonary Precancerous Condition
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2009
- Primary completion
- Feb 2012 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 16 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Prevention (erlotinib hydrochloride) | Experimental | Drug: Erlotinib Hydrochloride, Other: Laboratory Biomarker Analysis, Other: Pharmacological StudyPatients receive erlotinib hydrochloride PO QD for 90 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 40 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Erlotinib HydrochlorideAlso: Cp-358,774Given PO | Drug | Prevention (erlotinib hydrochloride) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Prevention (erlotinib hydrochloride) |
| Pharmacological StudyAlso: pharmacological studiesCorrelative studies | Other | Prevention (erlotinib hydrochloride) |
Primary outcome
Change in the ratio of p-EGFR to total EGFR
Time frame: Baseline up to 90 days
4 secondary outcomes
Change in the expression of p-Akt
Time frame: Baseline up to 90 days
Change in the expression of p-Erk
Time frame: Baseline up to 90 days
Change in the expression of Ki67
Time frame: Baseline up to 90 days
Incidence of toxicities, graded according to Common Toxicity Criteria, version 3.0
Time frame: Up to 30 days
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seema Khan principal investigator
Northwestern University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Erlotinib Hydrochloride, Laboratory Biomarker Analysis and Pharmacological Study in people with Dysplasia and Metaplasia, run by National Cancer Institute (NCI) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the ratio of p-EGFR to total EGFR (time frame: Baseline up to 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2015.