Paclitaxel and Carboplatin With or Without Celecoxib Before Surgery in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer

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.

Inclusion Criteria:

- Patients with biopsy proven non-small cell lung cancer clinical stage IIIA

- Mediastinoscopy positive N2 disease is mandatory

- The disease must be deemed potentially resectable by the thoracic surgeon

- Karnofsky performance status > 80%

- Pulmonary function must be acceptable for surgery according to institutional
standards

- Acceptable hepatic, renal and bone marrow function

- Total serum bilirubin < ULN

- AST and/or ALT < 2.5x ULN

- Alkaline phosphatase < 2.5x ULN

- Serum creatinine < 2.0 mg/mm3

- White blood cell > 3000/mm3

- Platelets > 100,000/mm3

- Age 18 or older

- Willingness to abstain from chronic use of NSAIDs (defined as > 7 days of continuous
therapy per month OR defined as frequency of > 3 times per week) for the duration of
the study. For those patients on NSAIDs prior to study entry, cessation of the drug
for 72 hours prior to study entry is required

- Patients on low-dose ASA (<325 mg daily) for prophylaxis of cardiovascular disease
prior to study entry may remain on that dose of ASA during this trial

- No anticipated chronic use of steroids. Patients may take the inhaled steroids
mometasone or fluticasone if medically indicated

Exclusion Criteria:

- Patients with known hypersensitivity or allergic reactions to COX-2 inhibitors,
sulfonamides, NSAIDs, or salicylates

- Hypersensitivity to paclitaxel

- Significant medical or psychiatric illness that would interfere with patient
compliance

- Prior malignancy within the last 3 years with the exception of non-melanoma skin
cancer

- Receiving other investigational agents during the course of this study or are < 3
weeks from completion of other clinical trial therapy

- Patients with a history of peptic ulcer disease, bleed disorder, irritable bowel
disease, inflammatory bowel syndrome, chronic diarrhea or bowel obstruction within 5
years

- Patients receiving enzyme-inducing anticonvulsants are ineligible. Patients who
require concomitant therapy with NSAIDs or COX-2 inhibitors

- Patients with any other serious underlying medical condition that would impair the
ability of the patient to receive or comply with protocol treatment

- Patients receiving lithium or fluconazole

- Pregnant women or women of childbearing potential that refuse to use effective
contraception during the period of chemotherapy.

- Patients with a significant history of unstable cardiovascular disease

- Uncontrolled diabetes mellitus or uncontrolled infection, including HIV or
interstitial pneumonia or interstitial fibrosis