RATIONALE: Drugs used in chemotherapy such as paclitaxel and carboplatin use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug, may stop the growth of tumor cells by stopping blood flow to the tumor, and/or may block the enzymes necessary for tumor cell growth. Giving combination chemotherapy with celecoxib before surgery may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining paclitaxel and carboplatin with or without celecoxib before surgery in treating patients who have stage IIIA non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
stage IIIA non-small cell lung cancer	Drug: carboplatin  Drug: celecoxib  Drug: paclitaxel  Procedure: adjuvant therapy  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: neoadjuvant therapy  Procedure: prostaglandin inhibition  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the complete pathological response rate and/or minimal residual microscopic disease in patients with stage IIIA non-small cell lung cancer treated with preoperative paclitaxel and carboplatin with vs without celecoxib.
• Compare the clinical response rate in patients treated with these regimens.
• Compare chemotherapy-related toxicity in patients treated with these regimens.
• Compare the time to progression, disease-free survival, and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to use of aspirin for prior cardiovascular disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on days 1, 22, and 43. Patients also receive oral celecoxib twice daily beginning on day 1 and continuing until the morning of surgical resection.
• Arm II: Patients receive paclitaxel and carboplatin as in arm I and an oral placebo twice daily beginning on day 1 and continuing until the morning of surgical resection. In both arms, patients undergo surgical resection and complete mediastinal lymph node dissection within 3-6 weeks after completion of chemotherapy. Patients resume oral celecoxib or placebo twice daily within 28-42 days after surgery and continue until 3 years from the date of randomization in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3-6 months.

PROJECTED ACCRUAL: A total of 110 patients (55 per treatment arm) will be accrued for this study.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer
• Stage IIIA
• Must have N2 disease by mediastinoscopy
• Potentially resectable

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• No bleeding disorder

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• AST and/or ALT less than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No significant history of unstable cardiovascular disease
• No inadequately controlled hypertension
• No angina
• No myocardial infarction within the past 6 months
• No ventricular cardiac arrhythmias requiring medication
• No congestive heart failure that would preclude study participation

Pulmonary

• Pulmonary function acceptable for surgery
• No interstitial pneumonia
• No interstitial fibrosis

Gastrointestinal

• No bowel obstruction within the past 5 years
• No history of peptic ulcer disease
• No irritable bowel disease
• No inflammatory bowel syndrome
• No chronic diarrhea

Immunologic

• No uncontrolled infection (including HIV)
• No known hypersensitivity or allergic reactions to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates
• No hypersensitivity to paclitaxel

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after study participation
• No uncontrolled diabetes mellitus
• No significant psychiatric illness that would preclude study compliance
• No other serious underlying medical condition that would preclude study therapy

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• No concurrent chronic steroids, except inhaled mometasone or fluticasone

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 72 hours since prior nonsteroidal anti-inflammatory drugs (NSAIDs)
• More than 3 weeks since other prior clinical trial therapy
• Concurrent low-dose aspirin (less than 325 mg every other day) for cardiovascular disease prophylaxis allowed
• No concurrent NSAIDs, including chronic use
• No concurrent cyclo-oxygenase-2 (COX-2) inhibitors
• No other concurrent investigational agents
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin or phenobarbital)
• No concurrent lithium
• No concurrent fluconazole

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-5907,  United States; Recruiting
New York
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000304540; UCLA-0208074; NYH-CMC-0902-464; PHARMACIA-COXAON-0509-106; NCT00062179
Record last reviewed:  September 2003
Last Updated:  December 6, 2004
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00062179
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08