Phase I/II Study of Chemoprevention With EGFR and COX-2 Inhibitor

Study Overview
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Brief Summary
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Evaluate effect on cells and patient response to study medications, assess side effects of these medications, and evaluate chemicals in cells that may tell how the drug works, before, and after receiving the study medications.

Detailed Description
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The purpose of this study is to evaluate the effect on cells and patient response to study medications, assess the side effects of these medications, and to evaluate chemicals in the cells that may tell how the drug works, before, and after receiving the study medications. Approximately 61 patients will participate at Emory Winship Cancer Institute and Emory Crawford W. Long Hospital in Atlanta, Georgia.

Official Title
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Phase I/II Study of Chemoprevention With Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Erlotinib (OSI-774, Tarceva) and Cyclooxygenase-2 (COX-2) Inhibitor (Celecoxib) in Premalignant Lesions of Head and Neck of Former Smokers

Conditions
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Precancerous Conditions

Intervention / Treatment
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* Drug: Erlotinib & Celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have premalignant lesions. Lesion sites include oral cavity, oropharynx, and larynx. Must have at least a >20 pack-year history of smoking. Must have a Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-1. Participants must be 18 years of age or older. No contraindications for laryngoscopy and biopsy. Adequate liver function. Must have hemoglobin and hematocrit levels at or above the lower limit of the normal range. Participants must have prothrombin time (PT)/partial thromboplastin time (PTT) levels at or above the lower limit of the normal range. Women of child-bearing potential must have a negative serum pregnancy test within 72 hours of receiving treatment. Must be able to swallow the oral dose of erlotinib and celecoxib. Participants must be disease free. Final eligibility will be determined by the health professionals conducting the trial. Exclusion Criteria: Participants with acute intercurrent illness or those who had surgery within the preceding 4 weeks unless they have fully recovered. History of previous malignancies unless the cancer was stage I or II and rendered free of disease more than 1 year. Pregnant or breast feeding. Not practicing adequate contraception if the participants are of child bearing potential. Female patients who have a positive pregnancy test. History or recent myocardial infarction. Hypertension not adequately controlled by medication. Documented history of coagulopathy. Documented history of congestive heart failure (CHF) greater than New York Heart Association (NYHA) Grade II. Participants who were taking COX-2 inhibitors or EGFR tyrosine kinase inhibitors within 3 months of study entry. Documented history or interstitial lung disease. Known connective tissue disease. History of nonsteroidal antiinflammatory drug (NSAID)-induced ulcers or those who are at risk for a GI ulcer. Participated in a clinical trial of an investigational drug within 12 months prior to enrollment. Final eligibility will be determined by the health professionals conducting the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib & Celecoxib<br> | Drug: Erlotinib & Celecoxib<br>* Erlotinib given orally, once daily (dose escalation from 50 mg, 75 mg, or 100 mg) continuously for 6 months in the phase I portion. Celecoxib given 400 mg orally BID continuously for 6 months.<br>* Other names: OSI-774, Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Participants received a fixed dose of celecoxib 400 mg orally BID continuously for 6 months. Erlotinib was dose escalated at 3 dose levels of 50, 75, and 100 mg orally every day for 6 months. Dose escalation followed a standard 3+3 escalation design. | 12 months from time of enrollment | 
| Clinical Outcome: Documented Progression | Response evaluation was based on pathologic examination of the degree of dysplasia observed and recorded by an expert head and neck pathologist. Pathologic complete response was defined as complete disappearance of dysplasia from the epithelium. Pathologic partial response was defined as improvement of dysplasia by at least one degree (i.e., severe dysplasia becomes moderate dysplasia). Pathologic minor response or stable disease was defined as minor focal improvement without change of degree of dysplasia (i.e., focal improvement from moderate to mild dysplasia with still moderate dysplasia overall) or no pathologic changes after treatment. Pathologic progressive disease was defined as worsening by at least one degree of dysplasia (i.e., mild to moderate dysplasia) or development of invasive cancer on or following treatment. | 12 months from time of enrollment | 
| Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma | Response evaluation was based on pathologic examination of the degree of dysplasia observed and recorded by an expert head and neck pathologist. Pathologic complete response was defined as complete disappearance of dysplasia from the epithelium. Pathologic partial response was defined as improvement of dysplasia by at least one degree (i.e., severe dysplasia becomes moderate dysplasia). Pathologic minor response or stable disease was defined as minor focal improvement without change of degree of dysplasia (i.e., focal improvement from moderate to mild dysplasia with still moderate dysplasia overall) or no pathologic changes after treatment. Pathologic progressive disease was defined as worsening by at least one degree of dysplasia (i.e., mild to moderate dysplasia) or development of invasive cancer on or following treatment. | Up to 55 months from initiation of therapy. Median duration of follow-up was 36 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skin Lesions, Premalignant Lesion