A Randomized Phase III Double Blind Trial Evaluating Selective COX-2 Inhibition in COX-2 Expressing Advanced Non-Small Cell Lung Cancer
A Randomized Phase III Double Blind Trial Evaluating Selective COX-2 Inhibition in COX-2 Expressing Advanced Non-Small Cell Lung Cancer
RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving gemcitabine hydrochloride or pemetrexed disodium together with carboplatin is more effective with or without celecoxib in treating non-small cell lung cancer.
PURPOSE: This randomized phase III trial is studying gemcitabine hydrochloride, pemetrexed disodium, and carboplatin to compare how well they work when given together with celecoxib or a placebo in treating patients with advanced non-small cell lung cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are stratified according to gender, disease stage (IIIB vs IV), histology (squamous cell carcinoma vs non-squamous cell carcinoma), smoking status (never/former light smoker [defined as ≤ 10 pack years AND quit ≥ 1 year ago] vs smoker), and COX-2 expression status (COX-2 index ≥ 4 vs COX-2 index ≥ 2 but < 4). Patients are randomized to 1 of 2 treatment arms.
In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with responding or stable disease may continue to receive celecoxib or placebo alone in the absence of disease progression or unacceptable toxicity.
Patients may undergo blood and urine sample collection periodically for correlative laboratory studies.
After completion of study therapy, patients are followed up every 2 months for 2 years and then every 6 months for 3 years.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed non-small cell carcinoma of the lung, including the following cell types:
A tissue block must be available at the time of registration
Tumor expresses COX-2 (COX-2 index ≥ 2)
Stage IIIB disease with malignant pleural effusion, supraclavicular node involvement, or contralateral hilar node involvement OR stage IV disease
Patients with stage IV disease are eligible
Patients with recurrent disease, not amenable to (or refusing) a potentially "curative therapy," are eligible
Measurable or non-measurable disease
Measurable disease is defined as lesions that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 2 cm with conventional techniques or as ≥ 1 cm with spiral CT scan
Non-measurable disease is defined as all other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly nonmeasurable lesions, including any of the following:
Patients with symptomatic CNS metastases are eligible provided they received prior therapy (e.g., surgery, radiotherapy, or gamma knife), are neurologically stable, and are off steroids for ≥ 14 days before study entry
No leptomeningeal disease or carcinomatous meningitis
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Granulocytes ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Creatinine clearance ≥ 45 mL/min
Bilirubin ≤ 1.5 mg/dL
AST and ALT ≤ 2.0 times upper limit of normal (ULN) (≤ 5.0 times ULN if liver metastases are present)
Serum albumin ≥ 2.5 mg/dL
Not pregnant or nursing
Negative pregnancy test
No "currently active" second malignancy other than non-melanoma skin cancer
No known hypersensitivity to aspirin, NSAIDs, or sulfonamides
No active ulcer disease
None of the following cardiovascular conditions within the past 6 months:
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
No prior chemotherapy, immunotherapy, or other systemic therapy for non-small cell lung cancer, including adjuvant therapy
At least 2 weeks since prior surgery and recovered
At least 7 days since prior radiotherapy
At least 14 days since prior NSAIDs (other than low-dose aspirin [≤ 325 mg daily]), including any of the following:
No chronic use of NSAIDs (i.e., > 4 weeks of daily use)
No other concurrent chemotherapy or hormonal therapy (other than megestrol acetate [Megace] for appetite stimulation)
No other concurrent investigational therapy
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