Erlotinib in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This clinical trial is studying how well erlotinib works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Prospectively identify downstream markers of EGFR linked signaling pathways that are predictive of response to OSI-774 (Erlotinib) in this population. SECONDARY OBJECTIVES: I. Estimate antitumor objective response rate per RECIST. II. Estimate disease control rate (CR+PR+SD). III. Estimate time to progression and overall survival. IV. Estimate if a grade 2 rash is a predictor of response to OSI-774 (Erlotinib) and of patient survival. V. Assess safety profile of OSI-774 (Erlotinib) in this population. VI. To determine whether smoking status is linked to outcome for advanced NSCLC patients treated with OSI-774 (Erlotinib). OUTLINE: This is a pilot, multicenter study. Patients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients complete the Smoking Status Survey, a questionnaire regarding smoking habits, at baseline, and then every 3 months during study treatment. After completion of study treatment, patients are followed every 3 months for 2 years, and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 129 patients will be accrued for this study within 6 months.

Official Title
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A Pilot Study to Determine if Downstream Markers of EGFR Linked Signaling Pathways Predict Response to OSI-774 (Erlotinib) in the First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have pathologically confirmed NSCLC Patients must have diagnostic specimen available on paraffin-embedded block Patients must have advanced NSCLC (stage IIIB with a malignant pleural effusion or IV disease, or recurrent disease) Patients must not have received prior chemotherapy or targeted therapy for metastatic disease, including no prior EGFR inhibitor; patient may have received adjuvant chemotherapy for early stage disease (IB-IIIA), or chemo/XRT for stage IIIA or IIIB disease, provided s/he meets all of the following: It has been at least 6 months since completion of patient's adjuvant chemotherapy for early stage disease (IB-IIIA) or chemo/XRT for stage IIIA or IIIB disease Patient now has advanced disease Patients must have measurable disease per RECIST criteria; all sites of disease must be assessed within 4 weeks prior to registration Creatinine < 1.5 mg/dL or a creatinine clearance of > 50 mL/min SGOT(AST) and SGPT(ALT) < 2 x the institution's upper limit of normal Bilirubin < 1.5 mg/dL ANC > 1500/mm^3 PLT > 100,000/mm^3 Patients must have ECOG performance status 0, 1, or 2 Patients with stable, treated brain metastases are eligible (defined as: patients with brain metastases must have been treated and are asymptomatic and are no longer taking corticosteroids) Patients with gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease, are ineligible Pregnant and breast feeding women are excluded from the study because the agent used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) for the duration of the study HIV positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774 (Erlotinib) Patients must not have had immuno, hormonal or radiation therapy within 2 weeks prior to entering the study; those who have not recovered from adverse events due to agents administered more than 2 weeks earlier are ineligible; previously irradiated areas can be considered measurable disease if there has been documented progression Patients must not have ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements Patients must not have serious non-healing wound, or bone fracture, or major surgical procedure within 21 days prior to study entry Patients taking Warfarin are eligible If the patient is taking Cyp3A4 inducers or inhibitors, they must be discontinued one week prior to starting OSI-774 (Erlotinib) Patients must not be enrolled in any other concurrent clinical trials

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 (erlotinib hydrochloride)<br>Patients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients complete the Smoking Status Survey, a questionnaire regarding smoking habits, at baseline, and then every 3 months during study treatment. | Drug: erlotinib hydrochloride<br>* Given orally<br>* Other names: OSI-774;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rates and distribution of the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (Erk)-phosphorylated expression groups based on the Response Evaluation Criteria in Solid Tumors (RECIST) | A Fisher's exact test with a two-sided 5% type I error rate will be calculated. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate based on the RECIST |  | Up to 5 years | 
| Disease control rate (complete response [CR]+partial response [PR]+stable disease [SD]) |  | Up to 8 weeks | 
| Time to progression |  | Date of entry on the study to the appearance of new metastatic lesions or objective tumor progression, up to 5 years | 
| Overall survival |  | Up to 5 years | 
| Toxicities associated with erlotinib hydrochloride, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 |  | Up to 5 years | 
| Relationship between clinical response and each of the markers using the semiquantitative histo-score method | Cox regression models will be used. | Baseline | 
| Effects of smoking status in terms of disease and survival | Descriptive and summary statistics will be conducted on the smoking questionnaire data. | Up to 5 years |