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

OBJECTIVES:

Primary

• Determine the biologically active dose of celecoxib administered with erlotinib in patients with stage IIIB or IV non-small cell lung cancer.
• Determine the toxicity profile of this regimen in these patients.

Secondary

• Determine the clinical activity of this regimen, in terms of reduction in tumor burden, in these patients.
• Correlate biological endpoints with cyclooxygenase-2 and epidermal growth factor receptor inhibition in patients treated with this regimen.

OUTLINE: This is a nonrandomized, dose-escalation study of celecoxib.

Patients receive oral erlotinib once daily and oral celecoxib twice daily on days 1-28. Treatment repeats every 4 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may continue treatment beyond 2 courses at the investigator's discretion.

Cohorts of 3-6 patients receive escalating doses of celecoxib until the maximum tolerated dose (MTD) and biologically active dose (BAD) are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). The BAD is defined as the maximum decrease in the level of PGE_2 where no DLT occurs.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 21-27 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer (NSCLC)

• Stage IIIB or IV
• Measurable disease
• Progressive disease after at least 2 prior standard chemotherapy regimens OR refused standard chemotherapy
• No active CNS metastases

PATIENT CHARACTERISTICS:

Age

• 21 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

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 2.5 times upper limit of normal (ULN)
• PT and/or PTT no greater than 1.5 times ULN

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• No New York Heart Association class III or IV cardiac disease
• No myocardial infarction within the past year
• No symptomatic ventricular arrhythmia
• No symptomatic conduction abnormality

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior gastrointestinal ulceration, bleeding, or perforation
• No hypersensitivity to celecoxib, sulfonamides, aspirin, other NSAIDs, or other reagents used in this study
• No concurrent disease or medical condition that would preclude study treatment or compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy

Endocrine therapy

• More than 4 weeks since prior corticosteroids
• No concurrent steroids (including chronic use)

• Concurrent topical steroids allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• More than 4 weeks since prior non-cytotoxic investigational agents
• More than 3 days since prior nonsteroidal anti-inflammatory drugs (NSAIDs)
• No prior cyclooxygenase-2 (COX-2) inhibitors for metastatic NSCLC
• No prior epidermal growth factor receptor inhibitor for metastatic NSCLC
• No concurrent COX-2 inhibitors
• No concurrent NSAIDs
• No concurrent fluconazole or lithium