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

November 13, 2009
April 9, 2014
October 2009
February 2012   (final data collection date for primary outcome measure)
Change in the ratio of p-EGFR to total EGFR [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01013831 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change in the expression of total EGFR and p-EGFR in lung biopsies before and after treatment [ Designated as safety issue: No ]
  • Change in the expression of p-Akt, p-Erk, Ki67, and Bcl2 [ Designated as safety issue: No ]
  • Pharmacokinetics and pharmacodynamics of erlotinib hydrochloride [ Designated as safety issue: No ]
  • Optimal biologic concentration of erlotinib hydrochloride [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
A Phase I Study of Erlotinib in Patients With Premalignant Lesions of the Lung

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.

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.

Interventional
Phase 1
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    Given orally
    Other Names:
    • CP-358,774
    • erlotinib
    • OSI-774
  • Other: laboratory biomarker analysis
    Correlative studies
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.

Interventions:
  • Drug: erlotinib hydrochloride
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
60
Not Provided
February 2012   (final data collection date for primary outcome measure)

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)
Both
40 Years to 79 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01013831
NCI-2013-00750, NCI-2013-00750, RPCI-I-121507, NU-NWU08-11-01, STU00012618, NCI 08-11-01, NWU08-11-01, N01CN35157, P30CA060553
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Raymond Bergan Northwestern University
National Cancer Institute (NCI)
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP