Gefitinib in Treating Patients With Previously Untreated Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well gefitinib works in treating patients with previously untreated stage IIIB or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the objective tumor response rate in patients with previously untreated stage IIIB or IV non-small cell lung cancer with somatic activating mutations in the TK region of the epidermal growth factor receptor (EGFR) gene treated with gefitinib. Secondary Determine response duration, progression-free survival, and overall survival of patients treated with this drug. Determine the safety of this drug in these patients. Compare the ability of various somatic activating mutations in the TK region of the EGFR gene to predict response in patients treated with this drug. Compare the ability of various somatic activating mutations in the TK region of the EGFR gene to predict toxicity of this drug in these patients. Define a molecular profile in patients who initially respond to treatment with this drug but subsequently progress on therapy. Determine the significance of germline polymorphisms of the EGFR gene, somatic amplification of the EGFR gene, and other molecular factors for their association with clinical outcome parameters in these patients. OUTLINE: This is an open-label study. Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 2 months. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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A Phase II, Open Label Study of Gefitinib (IRESSA) in Treatment-Naïve Subjects With Stage IIIB or IV Non-Small Cell Lung Cancer and Somatic Activating Mutations in the Epidermal Growth Factor Receptor

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: gefitinib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed non-small cell lung cancer (NSCLC) No squamous cell histology Stage IIIB (with pleural effusion) or stage IV disease Must meet ≥ 1 of the following criteria: Female Adenocarcinoma tumor histology No history of smoking, defined as smoking < 100 cigarettes (5 standard packs of cigarettes) in a lifetime, < 20 oz of pipe tobacco in a lifetime, OR < 100 cigars in a lifetime Asian/Pacific Rim ethnicity, defined as Japanese, Chinese, Korean, or other Asian/Pacific Rim ethnicity Must have activating mutations in the TK region of the epidermal growth factor receptor (EGFR) gene Measurable disease No symptomatic or newly diagnosed CNS metastases that have not been definitively treated with radiotherapy and/or surgery History of CNS metastases or cord compression allowed if definitively treated and clinically stable PATIENT CHARACTERISTICS: See Disease Characteristics ECOG performance status 0-2 Life expectancy ≥ 12 weeks Absolute neutrophil count ≥ 2,000/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.25 times upper limit of normal (ULN) ALT and AST ≤ 2.5 times ULN (5 times ULN if liver has tumor involvement) Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known severe hypersensitivity to gefitinib or any other component of gefitinib tablets No evidence of clinically active interstitial lung disease Patients with chronic, stable radiographic changes who are asymptomatic are eligible No other concurrent malignancy or malignancy diagnosed within the past 5 years except for basal cell carcinoma of the skin or cervical cancer in situ No concurrent severe or uncontrolled systemic disorder No evidence of any other significant clinical disorder or laboratory finding that, in the opinion of the investigator, would preclude study participation Able to tolerate protocol treatment, in the opinion of the investigator PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior systemic chemotherapy, biological therapy, immunotherapy, or hormonal therapy for NSCLC, including adjuvant and neoadjuvant treatment No prior radiotherapy to the target lesion Prior radiotherapy to bony disease or CNS disease allowed At least 2 weeks since prior radiotherapy and recovered More than 30 days since prior non-FDA approved or investigational agents No prior EGFR antagonists At least 2 weeks since prior and no concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum perforatum (St. John's wort) No concurrent chemotherapy, immunotherapy, hormonal therapy, nonpalliative radiotherapy, surgery for cancer, or other experimental medications No other concurrent specific antitumor therapy

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

| Intervention/Treatment |
| --- |
|Drug: gefitinib|oral drug taken daily around the same time|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response duration, progression-free survival, and overall survival |  |  | 
| Safety |  |  | 
| Ability of various somatic activating mutations in the TK region of the epidermal growth factor receptor (EGFR) gene to predict response and toxicity |  |  | 
| Molecular profile |  |  | 
| Significance of germline polymorphisms of the EGFR gene, somatic amplification of the EGFR gene, and other molecular factors for their association with clinical outcome parameters |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer, large cell lung cancer