Erlotinib Hydrochloride in Treating Patients With Previously Treated Non-Small Cell Lung Cancer, Head and Neck Cancer, or Esophageal Cancer and Precancerous Lesions of the Lung
This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01013831
First received: November 13, 2009
Last updated: May 1, 2013
Last verified: May 2013
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Purpose
This phase I trial is studying the side effects and best dose of erlotinib hydrochloride in treating patients with previously treated non-small cell lung cancer, head and neck cancer, or esophageal cancer 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.
| Condition | Intervention | Phase |
|---|---|---|
|
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 |
Drug: erlotinib hydrochloride Other: laboratory biomarker analysis Other: pharmacological study Other: pharmacogenomic studies |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung |
Resource links provided by NLM:
Genetics Home Reference related topics:
neuroblastoma
MedlinePlus related topics:
Benign Tumors
Cancer
Esophageal Cancer
Esophagus Disorders
Head and Neck Cancer
Lung Cancer
Tonsils and Adenoids
U.S. FDA Resources
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Change in the ratio of p-EGFR to total EGFR [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Changes in the expression of p-Akt, p-Erk, Ki67 in the lung biopsies [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]
- Incidence and severity of toxicities, graded according to Clinical Toxicity Criteria, version 3.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 60 |
| Study Start Date: | October 2009 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (erlotinib hydrochloride)
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. |
Drug: erlotinib hydrochloride
Given orally
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 40 Years to 79 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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)
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01013831
Locations
| United States, Illinois | |
| Northwestern University | |
| Chicago, Illinois, United States, 60611 | |
| United States, New York | |
| Roswell Park Cancer Institute | |
| Buffalo, New York, United States, 14263 | |
Sponsors and Collaborators
Investigators
| Principal Investigator: | Raymond Bergan | Northwestern University |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01013831 History of Changes |
| Other Study ID Numbers: | NCI-2013-00750, NCI 08-11-01, RPCI-I-121507, NU-NWU08-11-01, STU00012618, N01CN35157 |
| Study First Received: | November 13, 2009 |
| Last Updated: | May 1, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
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 Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms |
ClinicalTrials.gov processed this record on May 21, 2013