RATIONALE: Celecoxib may stop the growth of cancer by stopping blood flow to the tumor. Erlotinib and celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining celecoxib with erlotinib may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining celecoxib with erlotinib in treating patients who have stage IIIB or stage IV 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: erlotinib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase I

Further Study Details: 

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.

Ages Eligible for Study:  21 Years and above,  Genders Eligible for Study:  Both

Criteria

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

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095,  United States; Recruiting

Study chairs or principal investigators

Robert Alan Figlin, MD, FACP,  Principal Investigator,  Jonsson Comprehensive Cancer Center   
Karen Reckamp, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000335434; UCLA-0306083; NCT00072072
Record last reviewed:  October 2003
Last Updated:  April 4, 2005
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00072072
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08