Gemcitabine Hydrochloride or Pemetrexed Disodium and Carboplatin With or Without Celecoxib in Treating Patients With 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.
Drug: gemcitabine hydrochloride
Drug: pemetrexed disodium
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized Phase III Double Blind Trial Evaluating Selective COX-2 Inhibition in COX-2 Expressing Advanced Non-Small Cell Lung Cancer|
- Progression-free survival [ Time Frame: Time between randomization and disease relapse or death from any cause, assessed up to 5 years ]
- Overall survival [ Time Frame: Time between randomization and disease relapse or death from any cause, assessed up to 5 years ]
- Response rate [ Time Frame: Up to 5 years ]
- Toxicity [ Time Frame: Up to 5 years ]
- Comparison of survival benefit between patients with COX-2 index ≥ 2 treated with different treatment regimens [ Time Frame: Up to 5 years ]
- Adverse prognostic value of COX-2 expression [ Time Frame: Up to 5 years ]
|Study Start Date:||February 2010|
|Estimated Primary Completion Date:||January 2019 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive gemcitabine hydrochloride* IV on days 1 and 8 OR pemetrexed disodium* IV on day 1. Patients also receive carboplatin IV on day 1 and oral celecoxib twice daily on days 1-21.
Given IVDrug: celecoxib
Given orallyDrug: gemcitabine hydrochloride
Given IVDrug: pemetrexed disodium
Active Comparator: Arm II
Patients receive gemcitabine hydrochloride* OR pemetrexed disodium* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21.
Given IVDrug: gemcitabine hydrochloride
Given IVDrug: pemetrexed disodium
Given IVOther: placebo
- To confirm the beneficial effect of gemcitabine hydrochloride or pemetrexed disodium in combination with carboplatin with or without celecoxib in patients with advanced non-small cell lung cancer that expresses COX-2.
- To describe the response rate in patients treated with these regimens.
- To describe the distribution of progression-free survival (PFS) and overall survival of patients treated with these regimens.
- To compare the PFS of patients with COX-2 index ≥ 2 (adjusting for CYP2C9 genotype and celecoxib trough concentrations as covariates) treated with these regimens.
- To correlate urinary PGE-M level with COX-2 expression, COX-2 inhibition, and outcome.
- To evaluate the association between the -765G/C polymorphism in PTGS2 and COX-2 expression in non-small cell lung cancer specimens.
- To characterize a trough plasma celecoxib concentration which will be used as a measure of patient adherence to study treatment and which may be used in future studies for correlations with genotype and pharmacodynamic outcomes.
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.
- Arm I: Patients receive gemcitabine hydrochloride* IV on days 1 and 8 OR pemetrexed disodium* IV on day 1. Patients also receive carboplatin IV on day 1 and oral celecoxib twice daily on days 1-21.
- Arm II: Patients receive gemcitabine hydrochloride* OR pemetrexed disodium* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21.
- NOTE: *Patients with squamous cell carcinoma receive gemcitabine hydrochloride; patients with non-squamous cell carcinoma receive pemetrexed disodium.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01041781
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|Study Chair:||Martin J. Edelman, MD||University of Maryland Greenebaum Cancer Center|