Phase II Trial to Correlate Radiographic Response Induced By Gefitinib With Mutations in the Protein-Tyrosine Kinase Domain of the EGF Receptor Gene

Study Overview
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Brief Summary
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The purpose of this research study is to: see if gefitinib pills can shrink Stage 1 or 2 non-small cell lung cancers before surgery see if your non-small cell lung cancer has a mutation in a certain part of the EGFR gene see if patients whose tumor does shrink with gefitinib treatment are more likely to have a mutation in a certain part of the EGFR gene see if the pattern of protein expression in the blood is related to the tumor's sensitivity or resistance to gefitinib treatment. see if expression of certain genes in the tumor are related to the tumor's sensitivity or resistance to gefitinib treatment.

Detailed Description
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This is a phase II, single institution trial to correlate gefitinib response and mutations in the protein-tyrosine kinase domain of the EGF receptor gene. The study will be conducted in patients with Stage I and II NSCLC who have been determined to be operable and resectable. Patients must have 1 or more of the following features: never smoker or smoking history of < 15 pack years and/or features of bronchioloalveolar lung cancer. 50 patients will be enrolled on this study. Treatment will be with gefitinib for at least 21 days before surgery (depending on the timing of the surgery). Patients will discontinue gefitinib 2 days before their operation. For patients that demonstrate a radiographic response to gefitinib preoperatively and /or patients with mutations in the protein-tyrosine kinase domain of the EGF receptor gene (identified from the surgical sample), gefitinib will continue for 2 years post-surgery. Patients who do not have evidence of radiographic response or mutations in the protein-tyrosine kinase domain of the EGF receptor gene will be removed from the study.

Official Title
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Phase II Trial to Correlate Radiographic Response Induced By Gefitinib With Mutations in the Protein-Tyrosine Kinase Domain of the EGF Receptor Gene in Patients With NSCLC

Conditions
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Lung Cancer, Non-small Cell Lung Cancer, Bronchioloalveolar Cancer

Intervention / Treatment
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* Drug: Gefitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic confirmation of malignancy at Memorial Sloan-Kettering Patients must have previously untreated stage I or II NSCLC (T11-2N0M0, T1-2N1M0, T3N0M0) and 1 of the following features: never smoker or < 15 pack year smoking history and/or bronchioloalveolar cancer (either pure BAC, BAC with focal invasion or adenocarcinoma with BAC features) Patients must have been determined to be operable and resectable by the treating thoracic surgeon. Age >18 years. Measurable indicator lesions Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Pregnant or lactating women or women of childbearing potential not using effective contraception. Men participating in the trial must also use effective contraception when sexually active. Patients may not be receiving any other investigational agents. Any history of or evidence of interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded).

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: Gefitinib<br>* Patients will receive gefitinib 250 mg po daily for at least 21 days preoperatively (depending on the timing of the surgery). Treatment with gefitinib will be stopped 2 days before the date of surgery. Patients who have had at least a minor response to gefitinib therapy preoperatively (> 25% reduction in tumor measured bidimensionally) and / or have mutations in the protein-tyrosine kinase domain of the EGF receptor gene identified will continue on the study and will resume gefitinib treatment after at least 7 days from surgery providing adequate wound healing has occurred. Patients who are determined to be candidates for adjuvant chemotherapy and/or radiation therapy by their treating physician may receive treatment with adjuvant chemotherapy and/or radiation therapy. The post-operative gefitinib will be started after completion of the chemotherapy and/or radiation therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Radiographic Response to Gefitinib | Radiographic response is defined as a minor response ( > 25% decrease in the sum of the products of measured lesions) | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data | Each patient provides two binary variables: presence/absence of mutation and responder/non responder. The association between the two will be tested using the Fisher's exact test for the resulting 2x2 table.Changes in expression levels within a patient will be assessed using a paired t-test. Similarly differences in expression levels between responders and non-responders will be assessed using a two-sample t-test. Appropriate adjustment will be made for the multiple comparisons problem that arises because there are over 21,000 probe sets on the U133A array. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Lung Cancer, Non-small cell lung cancer, Gefitnib, Cancer, bronchioloalveolar cancer, smoker