RATIONALE: Celecoxib and gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase I trial to study the effectiveness of combining celecoxib with gefitinib in treating former smokers who have stage IIIB, stage IV, recurrent, or progressive non-small cell lung cancer

Condition	Treatment or Intervention	Phase
recurrent non-small cell lung cancer stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer	Drug: celecoxib  Drug: gefitinib  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: prostaglandin inhibition  Procedure: protein tyrosine kinase inhibitor therapy	Phase I

OBJECTIVES: Primary

• Determine the clinical toxicity and tolerability of celecoxib and gefitinib in former smokers with stage IIIB or IV or recurrent or progressive non-small cell lung cancer.

Secondary

• Determine the tumor response rate in patients treated with this regimen.
• Determine the dose of celecoxib that results in maximal induction of apoptosis, maximal inhibition of prostaglandin E_2 (PGE_2) in bronchoalveolar fluid, and maximal inhibition of bronchial cell proliferation in patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation study of celecoxib.

Patients receive oral gefitinib once daily and oral celecoxib twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of celecoxib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 6 additional patients are treated at the MTD.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 6-45 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following stage criteria:
• Stage IIIB with pleural effusion
• Stage IV disease
• Recurrent or progressive disease after prior surgery, radiotherapy, and/or chemotherapy
• Meets 1 of the following criteria:
• Untreated disease with epidermal growth factor receptor (EGFR) mutation
• Advanced NSCLC with at least stable disease after ≥ 4 courses of platinum-containing chemotherapy
• Relapsed or refractory disease after treatment with ≥ 1 prior platinum-containing chemotherapy program, including adjuvant or neoadjuvant therapy for NSCLC
• If the sole prior treatment was in the adjuvant or neoadjuvant setting, tumor progression or recurrence must have occurred within 6 months after completion of prior treatment
• Former smoker, as indicated by the following:
• At least a 30 pack-year smoking history
• Smoking duration at least 10 years
• At least 12 months of self-reported smoking cessation
• Negative urine cotinine
• No untreated brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Hemostasis normal

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• PT/PTT within 0.5 seconds of normal

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No significant cardiovascular disease
• No New York Heart Association class III or IV cardiac disease
• No uncontrolled dysrhythmia
• No unstable angina
• No myocardial infarction within the past 6 months

Pulmonary

• FEV_1 ≥ 1.0 liter OR 40% of predicted within the past 3 months
• Oxygen saturation ≥ 90% on room air

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study treatment
• Willing to undergo bronchoscopy
• No allergy to sulfonamides or hypersensitivity reaction to celecoxib
• No other medical or psychological condition (e.g., acute psychosis) that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin)

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery

• See Disease Characteristics
• Prior complete resection allowed provided there is histologic and cytologic documentation of disease recurrence

Other

• More than 3 months since prior chemopreventative agents (e.g., oltipraz, retinoids, or N-acetylcysteine [NAC])
• No prior geftinib
• No other prior EGFR antagonists
• No concurrent medication known to interact with gefitinib or celecoxib, including the following:
• Fluconazole
• Lithium
• Furosemide
• Angiotensin-converting enzyme inhibitors
• Phenytoin
• Carbamazepine
• Rifampin
• Barbiturates
• Hypericum perforatum (St. John's wort)
• No concurrent non-steroidal anti-inflammatory drugs
• Concurrent aspirin of up to an average dose of 325 mg/day allowed
• No aspirin treatment for 7 days prior to any bronchoscopic or skin biopsy
• No other concurrent EGFR inhibitors or cyclo-oxygenase-2 (COX-2) inhibitors

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27705,  United States; Recruiting
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States; Recruiting

Study chairs or principal investigators

Michael J. Kelley, MD,  Principal Investigator,  Duke Comprehensive Cancer Center   

Study ID Numbers:  CDR0000377689; DUMC-4939-04-6R1; DUMC-4939-03-6R0; VAMC-DURHAM-00813
Record last reviewed:  September 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00088959
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08