Official Title: “A Randomized, Placebo-Controlled Phase II Clinical Trial of Combination Erlotinib (Tarceva®) and Celecoxib (Celebrex®) Versus Erlotinib (Tarceva®)/Placebo in Advanced Non-Small Cell Lung Cancer Patients”

RATIONALE: Erlotinib and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Celecoxib may also stop the growth of lung cancer by blocking blood flow to the tumor. Giving erlotinib together with celecoxib may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving erlotinib together with celecoxib works compared with erlotinib alone in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

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.

Primary:

• Progression-free survival No

Secondary:

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

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

Lead Sponsor: Beckman Research Institute

City of Hope Comprehensive Cancer Center

Duarte California 91010-3000 United States

Overall Clinical Trial Officials and Contacts

Karen Reckamp, MD Principal Investigator Beckman Research Institute  

Information obtained from ClinicalTrials.gov on July 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00499655

Study ID Number: CDR0000549751

ClinicalTrials.gov Identifier: NCT00499655

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database