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: April 9, 2014
Last verified: April 2014
  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
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:


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 ]

Enrollment: 60
Study Start Date: October 2009
Primary Completion Date: February 2012 (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:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies

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-2013-00750, RPCI-I-121507, NU-NWU08-11-01, STU00012618, NCI 08-11-01, NWU08-11-01, N01CN35157, P30CA060553
Study First Received: November 13, 2009
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Basal Cell
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Carcinoma, Adenoid Cystic
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
Neoplasms, Basal Cell
Carcinoma, Bronchogenic

ClinicalTrials.gov processed this record on April 21, 2014