De Novo Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

Study Overview
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Brief Summary
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This study is based on the following hypothesis De novo resistance to EGFR-TKI in EGFR mutation positive patients is related with mutations in EGFR downstream genes. Investigators will prospectively collect genomic DNA and clinical data regarding treatment outcomes to EGFR-TKI in NSCLC patients with activating EGFR mutations. Investigators will sequence candidate mutations of EGFR downstream genes and analyze c-met gene amplification and protein expression in PTEN, HGF, and IGFR. To identify genetic mutations, amplification, and protein over expression as predictive markers of treatment outcomes, investigators analyzed the association of treatment outcomes with the presence of genetic alteration or protein over expression. Investigators will attempt to identify biomarkers that are able to predict de novo resistance to EGFR-TKI in EGFR mutated NSCLC.

Detailed Description
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Investigators will prospectively enroll patients who match the following criteria: pathologically proven unresectable NSCLC, planning to treat with EGFR-TKI, patients with activating EGFR mutations, and available tissue sample for DNA extraction.

Official Title
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Pilot Study to Identify the Mechanism of De Novo Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) in NSCLC With EGFR Mutation.

Conditions
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NSCLC

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven unresectable NSCLC 20 years of age or older Planned treatment with Iressa® Patients with activating EGFR mutation (del 19, L858R) Available detailed smoking history Available tissue samples (archival tissue) for mutational or molecular analysis (representative paraffin block or unstained sections from tumor diagnostic specimen are mandatory) Available blood sample At least one lesion that is measurable according to the RECIST 1.1 criteria by CT or MRI Written informed consent Exclusion Criteria: More than 3rd line treatment Previously treated with other EGFR-TKI Life expectancy of less than 12 weeks Pregnant or lactating female Any unresolved toxicity greater than CTC grade 2 (version 4.0) from previous anti cancer treatment. Unsuitable patient in this treatment as determined by doctor.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Iressa<br>Lung cancer patients with EGFR mutation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hazard rates of PFS | The primary objective is to compare hazard rates of PFS in patients treated with Iressa between with and without any molecular aberrancy in EGFR-downstream genes/proteins. | 1year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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De Novo Resistance, Iressa, EGFR mutation, lung cancer