• Progression-free survival [ Designated as safety issue: No ]
  

• Time to disease progression [ Designated as safety issue: No ]
  
• Response as assessed by CT scan/fludeoxyglucose F 18-PET activity at weeks 0, 4, and 8 [ Designated as safety issue: No ]
  
• Urinary prostaglandin E-metabolite levels [ Designated as safety issue: No ]
  
• Measurement of EGFR, cyclooxygenase (COX)-2 in relationship to tumor response as assessed by RECIST criteria at 8 weeks [ Designated as safety issue: No ]
  
• Other Cox-2 and EGFR-dependent markers [ Designated as safety issue: No ]
  
• Mutation status [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the progression-free survival of patients with stage IIIB or IV non-small cell lung cancer treated with erlotinib hydrochloride with versus without celecoxib.

Secondary

• Compare the objective tumor response rate in patients treated with these regimens.
• Correlate response (including stable disease) with fludeoxyglucose F 18 positron emission tomography (FDG-PET) activity from baseline to weeks 4 and 8 in patients treated with these regimens.
• Determine the change in E-cadherin expression from baseline to week 8 in patients treated with these regimens.
• Compare the overall survival of patients treated with these regimens.
• Correlate cyclooxygenase-2, EGFR by immunohistochemistry, EGFR amplification by FISH, and EGFR mutation status with clinical response in patients treated with these regimens.
• Correlate the change in urinary prostaglandin E-metabolite with response in patients treated with these regimens.

OUTLINE: This is a multicenter, randomized, placebo-controlled, double-blind study. Patients are stratified according to smoking status (nonsmoker [< 100 cigarettes smoked in lifetime] vs current/former smoker) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral erlotinib hydrochloride once daily and oral placebo twice daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral celecoxib twice daily and oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood, tissue, and urine collection at baseline and weeks 4 and 8 for biological studies. Samples are analyzed for cyclooxygenase-2 and EGFR gene expression and prostaglandin E-metabolite via immunohistochemistry and fluorescence in situ hybridization (FISH).

After completion of study treatment, patients are followed every 2 months.

DISEASE CHARACTERISTICS:

• Pathologically confirmed non-small cell lung cancer

  • Stage IIIB or IV disease
• Measurable disease
• Must have tumor tissue available
• Progressive disease despite ≥ 1 prior chemotherapy regimen as standard of care OR patient has refused or is not able to receive standard chemotherapy
• No active CNS metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• PT/PTT ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• Creatinine ≤ 2 mg/dL
• AST and ALT ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 1 week after completion of study treatment

• No other condition including any of the following:

  • New York Heart Association class III-IV cardiac disease
  • History of myocardial infarction
  • Cerebrovascular accident
  • Symptomatic ventricular arrhythmia
  • Symptomatic conduction abnormality
• No comorbid disease or medical condition that would preclude study therapy
• No other malignancy within the past 3 years except for nonmelanoma skin cancer or carcinoma in situ of the cervix
• No hypersensitivity to erlotinib hydrochloride, celecoxib, or any excipients
• No hypersensitivity to sulfonamides, acetylsalicylic acid, or other NSAIDs
• No history of gastrointestinal ulceration, bleeding, or perforation

• No clinically active interstitial lung disease

  • Asymptomatic patients with chronic stable radiographic changes eligible

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy, chemotherapy, or noncytotoxic investigational agents
• At least 72 hours since prior NSAIDs
• No prior EGFR inhibitor for the treatment of cancer
• No other concurrent cyclooxygenase-2 inhibitors or NSAIDs

• No concurrent or chronic use of steroids

  • Topical steroids allowed
• No concurrent fluconazole or lithium carbonate