Gefitinib and Celecoxib in Treating Patients With Refractory Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Determine the response rate in patients with platinum-refractory non-small cell lung cancer treated with gefitinib and celecoxib.

Secondary

• Determine the progression-free and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: Patients receive oral gefitinib once daily and oral celecoxib twice daily on days 1-28. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for up to 6 weeks.

PROJECTED ACCRUAL: A total of 18-27 patients will be accrued for this study within 22 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
• Progression of disease during platinum-based (cisplatin or carboplatin) chemotherapy or within 3 months of completing chemotherapy

• Treatment with other agents since prior platinum-based chemotherapy allowed
• Measurable disease

• Target lesions within a prior radiation field must have documented evidence of progression at least 8 weeks after the completion of radiotherapy
• No active brain or leptomeningeal metastases

• Treated brain metastases allowed at least 4 weeks after the completion of appropriate therapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8 g/dL

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN (if alkaline phosphatase is no greater than ULN)
• Alkaline phosphatase no greater than 5 times ULN (if AST and ALT are greater than ULN)
• No history of chronic hepatitis

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No active thromboembolic event within the past 4 weeks
• No uncontrolled congestive heart failure
• No uncontrolled angina
• No myocardial infarction and/or stroke within the past 6 months

Pulmonary

• No evidence of clinically active interstitial lung disease

Gastrointestinal

• No history of gastrointestinal bleeding within the past 6 months
• No history of peptic ulcer disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must weigh at least 110 pounds (50 kg)
• HIV negative
• No allergy to sulfonamides
• No allergy to any NSAID, including celecoxib
• No known severe hypersensitivity to gefitinib or any of its excipients
• No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No history of dementia, active psychiatric disorder, or any other condition that would preclude study compliance
• No other concurrent serious medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior epidermal growth factor receptor inhibitor
• No concurrent biologic therapy

Chemotherapy

• See Disease Characteristics
• More than 2 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Recovered from prior radiotherapy

Surgery

• Recovered from prior surgery

Other

• Recovered from prior therapy
• More than 2 weeks since prior investigational therapy
• More than 1 week since prior fluconazole
• More than 30 days since prior participation in another investigational agent clinical trial
• More than 30 days since prior chronic nonsteroidal anti-inflammatory drugs (NSAIDs), including celecoxib or rofecoxib
• No prior gefitinib
• No prior cyclooxygenase-2 (COX-2) inhibitor or another clinical trial for NSCLC
• No other concurrent NSAIDs

• Concurrent aspirin allowed (not to exceed 325 mg/day)
• No other concurrent COX-2 inhibitors
• No concurrent lithium
• No concurrent fluconazole
• No concurrent use of any of the following:

• Phenytoin
• Carbamazepine
• Barbiturates
• Rifampin
• Phenobarbital
• Hypericum perforatum