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

Study Overview
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Brief Summary
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This phase II trial is studying how well giving erlotinib together with celecoxib works in treating patients with recurrent stage IIIB or stage IV non-small cell lung cancer. Erlotinib and celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Celecoxib may slow the growth of a tumor by stopping blood flow to the tumor. Combining erlotinib with celecoxib may kill more tumor cells. .

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the response rate of patients with stage IIIB or IV recurrent non-small cell lung cancer treated with erlotinib and celecoxib as second-line therapy. SECONDARY OBJECTIVES: I. Determine the time to progression in patients treated with this regimen. II. Determine the survival duration of patients treated with this regimen. III. Determine the toxicity of this regimen in these patients. IV. Correlate the expression of epidermal growth factor receptor and cyclooxygenase-2 in tumor specimens with response, time to progression, and survival in patients treated with this regimen. OUTLINE: Patients are assigned to 1 of 2 treatment groups. Group 1: Patients receive oral erlotinib once daily and oral celecoxib twice daily. Group 2: Patients receive erlotinib as in group 1. Treatment in both groups continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 40-80 patients will be accrued for this study within 10 months.

Official Title
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A Phase II Study of OSI 774 (IND Number 63383) in Combination With Celecoxib (Celebrex, Pharmacia) as Second-Line Therapy in 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
* Drug: celecoxib
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed non-small cell lung cancer Stage IIIB (malignant pleural effusion only) or IV Recurrent disease that has progressed after 1 or 2 prior chemotherapy regimens (platinum- or nonplatinum-based) At least 1 unidimensionally measurable lesion* At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan Must have tissue specimen available for assays No brain metastases Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 3 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin normal AST/ALT no greater than 2.5 times upper normal limit (ULN) Creatinine normal Creatinine clearance at least 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No prior abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome) No congenital abnormality (e.g., Fuch's dystrophy) No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose) No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test) Able to ingest oral medication No requirement for IV alimentation No history of peptic ulcer disease No active gastrointestinal ulcers Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other concurrent uncontrolled illness No ongoing or active infection No significant traumatic injury within the past 21 days No psychiatric illness or social situation that would preclude study compliance No prior allergic reactions to sulfonamides, aspirin, and other nonsteroidal anti-inflammatory drugs No prior monoclonal antibodies to epidermal growth factor receptor (EGFR) More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No concurrent chemotherapy No concurrent glucocorticoids More than 4 weeks since prior radiotherapy and recovered More than 21 days since prior major surgery No prior surgery affecting absorption No prior EGFR-specific tyrosine kinases No concurrent anticonvulsants No other concurrent investigational agents No concurrent antiretroviral therapy for HIV-positive patients No concurrent antacids No concurrent administration of any of the following drugs: Amiodarone Chloramphenicol Cimetidine Fluvoxamine Omeprazole Zafirlukast Clopidogrel Cotrimoxazole Disulfiram Fluconazole Fluoxetine Fluvastatin Fluvoxamine Isoniazid Itraconazole Ketoconazole Leflunomide Metronidazole Modafinil Paroxetine Phenylbutazone Sertraline Ticlopidine Valproic acid

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (erlotinib hydrochloride, celecoxib)<br>Patients receive oral erlotinib once daily and oral celecoxib twice daily. | Drug: erlotinib hydrochloride<br>* Given orally (PO)<br>* Other names: OSI-774;Drug: celecoxib<br>* Given PO<br>* Other names: SC-58635;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Group II (erlotinib hydrochloride)<br>Patients receive erlotinib as in group 1. | Drug: erlotinib hydrochloride<br>* Given orally (PO)<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 rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) |  | From the start of treatment until disease progression/recurrence, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | Will be analyzed by calculating Kaplan Meier curves and estimating medians and 95% confidence intervals using the method of Brookmeyer and Crowley. | Interval between start of treatment with erlotinib hydrochloride and celecoxib and the date on which progressive disease, assessed up to 5 years | 
| Overall survival | Will be analyzed by calculating Kaplan Meier curves and estimating medians and 95% confidence intervals using the method of Brookmeyer and Crowley. | Up to 5 years | 
| Relationship between measures of treatment efficacy and EGFR and COX-2 levels |  | Up to 5 years | 
| Toxicity as assessed by NCI Common Toxicity Criteria (CTC) version 2.0 |  | Up to 5 years |