A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung
Phase 1
40 Years
79 Years
40 Years
79 Years
Open (Enrolling)
Both
High-grade Salivary Gland Mucoepidermoid Carcinoma, Low-grade Salivary Gland Mucoepidermoid Carcinoma, Occult Non-small Cell Lung Cancer, Salivary Gland Acinic Cell Tumor, Salivary Gland Adenocarcinoma, Salivary Gland Adenoid Cystic Carcinoma, Salivary Gland Anaplastic Carcinoma, Salivary Gland Malignant Mixed Cell Type Tumor, Salivary Gland Poorly Differentiated Carcinoma, Salivary Gland Squamous Cell Carcinoma, Squamous Lung Dysplasia, Stage 0 Esophageal Cancer, Stage 0 Non-small Cell Lung Cancer, Stage I Adenoid Cystic Carcinoma of the Oral Cavity, Stage I Basal Cell Carcinoma of the Lip, Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage I Lymphoepithelioma of the Nasopharynx, Stage I Lymphoepithelioma of the Oropharynx, Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage I Mucoepidermoid Carcinoma of the Oral Cavity, Stage I Non-small Cell Lung Cancer, Stage I Salivary Gland Cancer, Stage I Squamous Cell Carcinoma of the Hypopharynx, Stage I Squamous Cell Carcinoma of the Larynx, Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage I Squamous Cell Carcinoma of the Nasopharynx, Stage I Squamous Cell Carcinoma of the Oropharynx, Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage I Verrucous Carcinoma of the Larynx, Stage I Verrucous Carcinoma of the Oral Cavity, Stage IA Esophageal Cancer, Stage IB Esophageal Cancer, Stage II Adenoid Cystic Carcinoma of the Oral Cavity, Stage II Basal Cell Carcinoma of the Lip, Stage II Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage II Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage II Lymphoepithelioma of the Nasopharynx, Stage II Lymphoepithelioma of the Oropharynx, Stage II Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage II Mucoepidermoid Carcinoma of the Oral Cavity, Stage II Non-small Cell Lung Cancer, Stage II Salivary Gland Cancer, Stage II Squamous Cell Carcinoma of the Hypopharynx, Stage II Squamous Cell Carcinoma of the Larynx, Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage II Squamous Cell Carcinoma of the Nasopharynx, Stage II Squamous Cell Carcinoma of the Oropharynx, Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage II Verrucous Carcinoma of the Larynx, Stage II Verrucous Carcinoma of the Oral Cavity, Stage IIA Esophageal Cancer, Stage IIB Esophageal Cancer, Stage III Adenoid Cystic Carcinoma of the Oral Cavity, Stage III Basal Cell Carcinoma of the Lip, Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage III Lymphoepithelioma of the Nasopharynx, Stage III Lymphoepithelioma of the Oropharynx, Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage III Mucoepidermoid Carcinoma of the Oral Cavity, Stage III Salivary Gland Cancer, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IIIA Esophageal Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Esophageal Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IIIC Esophageal Cancer, Stage IV Adenoid Cystic Carcinoma of the Oral Cavity, Stage IV Basal Cell Carcinoma of the Lip, Stage IV Esophageal Cancer, Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Lymphoepithelioma of the Oropharynx, Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IV Mucoepidermoid Carcinoma of the Oral Cavity, Stage IV Non-small Cell Lung Cancer, Stage IV Salivary Gland Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Verrucous Carcinoma of the Larynx, Stage IV Verrucous Carcinoma of the Oral Cavity, Tongue Cancer
Both
High-grade Salivary Gland Mucoepidermoid Carcinoma, Low-grade Salivary Gland Mucoepidermoid Carcinoma, Occult Non-small Cell Lung Cancer, Salivary Gland Acinic Cell Tumor, Salivary Gland Adenocarcinoma, Salivary Gland Adenoid Cystic Carcinoma, Salivary Gland Anaplastic Carcinoma, Salivary Gland Malignant Mixed Cell Type Tumor, Salivary Gland Poorly Differentiated Carcinoma, Salivary Gland Squamous Cell Carcinoma, Squamous Lung Dysplasia, Stage 0 Esophageal Cancer, Stage 0 Non-small Cell Lung Cancer, Stage I Adenoid Cystic Carcinoma of the Oral Cavity, Stage I Basal Cell Carcinoma of the Lip, Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage I Lymphoepithelioma of the Nasopharynx, Stage I Lymphoepithelioma of the Oropharynx, Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage I Mucoepidermoid Carcinoma of the Oral Cavity, Stage I Non-small Cell Lung Cancer, Stage I Salivary Gland Cancer, Stage I Squamous Cell Carcinoma of the Hypopharynx, Stage I Squamous Cell Carcinoma of the Larynx, Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage I Squamous Cell Carcinoma of the Nasopharynx, Stage I Squamous Cell Carcinoma of the Oropharynx, Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage I Verrucous Carcinoma of the Larynx, Stage I Verrucous Carcinoma of the Oral Cavity, Stage IA Esophageal Cancer, Stage IB Esophageal Cancer, Stage II Adenoid Cystic Carcinoma of the Oral Cavity, Stage II Basal Cell Carcinoma of the Lip, Stage II Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage II Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage II Lymphoepithelioma of the Nasopharynx, Stage II Lymphoepithelioma of the Oropharynx, Stage II Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage II Mucoepidermoid Carcinoma of the Oral Cavity, Stage II Non-small Cell Lung Cancer, Stage II Salivary Gland Cancer, Stage II Squamous Cell Carcinoma of the Hypopharynx, Stage II Squamous Cell Carcinoma of the Larynx, Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage II Squamous Cell Carcinoma of the Nasopharynx, Stage II Squamous Cell Carcinoma of the Oropharynx, Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage II Verrucous Carcinoma of the Larynx, Stage II Verrucous Carcinoma of the Oral Cavity, Stage IIA Esophageal Cancer, Stage IIB Esophageal Cancer, Stage III Adenoid Cystic Carcinoma of the Oral Cavity, Stage III Basal Cell Carcinoma of the Lip, Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage III Lymphoepithelioma of the Nasopharynx, Stage III Lymphoepithelioma of the Oropharynx, Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage III Mucoepidermoid Carcinoma of the Oral Cavity, Stage III Salivary Gland Cancer, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IIIA Esophageal Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Esophageal Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IIIC Esophageal Cancer, Stage IV Adenoid Cystic Carcinoma of the Oral Cavity, Stage IV Basal Cell Carcinoma of the Lip, Stage IV Esophageal Cancer, Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Lymphoepithelioma of the Oropharynx, Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IV Mucoepidermoid Carcinoma of the Oral Cavity, Stage IV Non-small Cell Lung Cancer, Stage IV Salivary Gland Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Verrucous Carcinoma of the Larynx, Stage IV Verrucous Carcinoma of the Oral Cavity, Tongue Cancer
Trial Information
A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung
PRIMARY OBJECTIVES:
I. To determine the lowest dose of erlotinib that will decrease the ratio of phosphorylated
to total 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-Akt, p-Erk, and 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 are stratified according to smoking status (current vs former/never
smokers).
Patients receive oral erlotinib hydrochloride once daily for 90 days in the absence of
disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for correlative biomarker,
pharmacokinetic, and pharmacogenetic studies.
After completion of study treatment, patients are followed up at 30 days.
Inclusion Criteria:
- Diagnosis of a premalignant lung lesion (metaplasia or dysplasia) on 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
- 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
- AST and ALT =< 1.5 x ULN
- Alkaline phosphatase =< 2.5 x ULN
- Must meet ECOG performance status criteria of 0-1
- The effects of erlotinib on the developing human fetus at the recommended therapeutic
dose are unknown; for this reason 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;
ff she is pregnant, she will be immediately withdrawn from the study
- Ability to understand and the willingness to sign a written 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 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)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Change in the ratio of p-EGFR to total EGFR
Outcome Time Frame:
Up to 90 days
Safety Issue:
No
Principal Investigator
Raymond Bergan
Investigator Role:
Principal Investigator
Investigator Affiliation:
Northwestern University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2013-00750
NCT ID:
NCT01013831
Start Date:
October 2009
Completion Date:
Related Keywords:
- High-grade Salivary Gland Mucoepidermoid Carcinoma
- Low-grade Salivary Gland Mucoepidermoid Carcinoma
- Occult Non-small Cell Lung Cancer
- Salivary Gland Acinic Cell Tumor
- Salivary Gland Adenocarcinoma
- Salivary Gland Adenoid Cystic Carcinoma
- Salivary Gland Anaplastic Carcinoma
- Salivary Gland Malignant Mixed Cell Type Tumor
- Salivary Gland Poorly Differentiated Carcinoma
- Salivary Gland Squamous Cell Carcinoma
- Squamous Lung Dysplasia
- Stage 0 Esophageal Cancer
- Stage 0 Non-small Cell Lung Cancer
- Stage I Adenoid Cystic Carcinoma of the Oral Cavity
- Stage I Basal Cell Carcinoma of the Lip
- Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Stage I Lymphoepithelioma of the Nasopharynx
- Stage I Lymphoepithelioma of the Oropharynx
- Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Stage I Mucoepidermoid Carcinoma of the Oral Cavity
- Stage I Non-small Cell Lung Cancer
- Stage I Salivary Gland Cancer
- Stage I Squamous Cell Carcinoma of the Hypopharynx
- Stage I Squamous Cell Carcinoma of the Larynx
- Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage I Squamous Cell Carcinoma of the Nasopharynx
- Stage I Squamous Cell Carcinoma of the Oropharynx
- Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Stage I Verrucous Carcinoma of the Larynx
- Stage I Verrucous Carcinoma of the Oral Cavity
- Stage IA Esophageal Cancer
- Stage IB Esophageal Cancer
- Stage II Adenoid Cystic Carcinoma of the Oral Cavity
- Stage II Basal Cell Carcinoma of the Lip
- Stage II Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Stage II Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Stage II Lymphoepithelioma of the Nasopharynx
- Stage II Lymphoepithelioma of the Oropharynx
- Stage II Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Stage II Mucoepidermoid Carcinoma of the Oral Cavity
- Stage II Non-Small Cell Lung Cancer
- Stage II Salivary Gland Cancer
- Stage II Squamous Cell Carcinoma of the Hypopharynx
- Stage II Squamous Cell Carcinoma of the Larynx
- Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage II Squamous Cell Carcinoma of the Nasopharynx
- Stage II Squamous Cell Carcinoma of the Oropharynx
- Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Stage II Verrucous Carcinoma of the Larynx
- Stage II Verrucous Carcinoma of the Oral Cavity
- Stage IIA Esophageal Cancer
- Stage IIB Esophageal Cancer
- Stage III Adenoid Cystic Carcinoma of the Oral Cavity
- Stage III Basal Cell Carcinoma of the Lip
- Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Stage III Lymphoepithelioma of the Nasopharynx
- Stage III Lymphoepithelioma of the Oropharynx
- Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Stage III Mucoepidermoid Carcinoma of the Oral Cavity
- Stage III Salivary Gland Cancer
- Stage III Squamous Cell Carcinoma of the Hypopharynx
- Stage III Squamous Cell Carcinoma of the Larynx
- Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage III Squamous Cell Carcinoma of the Nasopharynx
- Stage III Squamous Cell Carcinoma of the Oropharynx
- Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Stage III Verrucous Carcinoma of the Larynx
- Stage III Verrucous Carcinoma of the Oral Cavity
- Stage IIIA Esophageal Cancer
- Stage IIIA Non-Small Cell Lung Cancer
- Stage IIIB Esophageal Cancer
- Stage IIIB Non-Small Cell Lung Cancer
- Stage IIIC Esophageal Cancer
- Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
- Stage IV Basal Cell Carcinoma of the Lip
- Stage IV Esophageal Cancer
- Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Stage IV Lymphoepithelioma of the Nasopharynx
- Stage IV Lymphoepithelioma of the Oropharynx
- Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Stage IV Mucoepidermoid Carcinoma of the Oral Cavity
- Stage IV Non-Small Cell Lung Cancer
- Stage IV Salivary Gland Cancer
- Stage IV Squamous Cell Carcinoma of the Hypopharynx
- Stage IV Squamous Cell Carcinoma of the Larynx
- Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage IV Squamous Cell Carcinoma of the Nasopharynx
- Stage IV Squamous Cell Carcinoma of the Oropharynx
- Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Stage IV Verrucous Carcinoma of the Larynx
- Stage IV Verrucous Carcinoma of the Oral Cavity
- Tongue Cancer
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Carcinoma
- Carcinoma, Basal Cell
- Carcinoma, Non-Small-Cell Lung
- Carcinoma, Squamous Cell
- Carcinoma, Adenoid Cystic
- Esophageal Diseases
- Esophageal Neoplasms
- Granuloma
- Head and Neck Neoplasms
- Laryngeal Diseases
- Lung Neoplasms
- Papilloma
- Tongue Neoplasms
- Carcinoma in Situ
- Carcinoma, Acinar Cell
- Carcinoma, Mucoepidermoid
- Carcinoma, Verrucous
- Esthesioneuroblastoma, Olfactory
- Papilloma, Inverted
- Salivary Gland Neoplasms
- Hypopharyngeal Neoplasms
- Laryngeal Neoplasms
- Paranasal Sinus Neoplasms
- Oropharyngeal Neoplasms
- Nasopharyngeal Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Northwestern University | Chicago, Illinois 60611 |
