Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Erlotinib With or Without Celecoxib in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Active	Over 18	NCI, Pharmaceutical / Industry	CHNMC-06254 IRB #06254, NCT00499655

Objectives

Primary

1. 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

1. Compare the objective tumor response rate in patients treated with these regimens.
2. 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.
3. Determine the change in E-cadherin expression from baseline to week 8 in patients treated with these regimens.
4. Compare the overall survival of patients treated with these regimens.
5. Correlate cyclooxygenase-2, EGFR by immunohistochemistry, EGFR amplification by FISH, and EGFR mutation status with clinical response in patients treated with these regimens.
6. Correlate the change in urinary prostaglandin E-metabolite with response in patients treated with these regimens.

Entry Criteria

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

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

Patient Characteristics:

• ECOG performance status 0-1
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

Outcomes

Progression-free survival

Time to disease progression
Response as assessed by CT scan/fludeoxyglucose F 18-PET activity at weeks 0, 4, and 8
Urinary prostaglandin E-metabolite levels
Measurement of EGFR, cyclooxygenase (COX)-2 in relationship to tumor response as assessed by RECIST criteria at 8 weeks
Other Cox-2 and EGFR-dependent markers
Mutation status

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.

Trial Contact Information

Trial Lead Organizations

City of Hope Comprehensive Cancer Center

Karen Reckamp, MD, MS, Principal investigator		Ph: 626-359-8111; 800-826-4673

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Karen Reckamp, MD, MS	Ph:  800-826-4673
	Pasedena
	City of Hope Medical Group
		Contact Person	Ph:  626-396-2900

Registry Information
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
Trial Start Date		2007-11-02
Trial Completion Date		2009-07-31 (estimated)
Registered in ClinicalTrials.gov		NCT00499655
Date Submitted to PDQ		2007-05-10
Information Last Verified		2008-12-07
NCI Grant/Contract Number		CA090388, CA33572

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