Gemcitabine Hydrochloride or Pemetrexed Disodium and Carboplatin With or Without Celecoxib in Treating Patients With Advanced Non-Small Cell Lung Cancer
- Conditions
- Lung Cancer
- Interventions
- Registration Number
- NCT01041781
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 313
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I gemcitabine hydrochloride 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 gemcitabine hydrochloride Patients receive gemcitabine hydrochloride\* OR pemetrexed disodium\* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21. Arm II placebo Patients receive gemcitabine hydrochloride\* OR pemetrexed disodium\* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21. Arm I pemetrexed disodium 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 pemetrexed disodium Patients receive gemcitabine hydrochloride\* OR pemetrexed disodium\* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21. Arm I carboplatin 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 I celecoxib 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 carboplatin Patients receive gemcitabine hydrochloride\* OR pemetrexed disodium\* and carboplatin as in arm I. Patients also receive oral placebo twice daily on days 1-21.
- Primary Outcome Measures
Name Time Method Progression-free Survival Time between randomization and disease relapse or death from any cause, assessed up to 5 years Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
- Secondary Outcome Measures
Name Time Method Overall Survival Time between randomization and death from any cause, assessed up to 5 years Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Response Rate Up to 5 years The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. Response rates (including complete and partial response) will be tested using Fisher's exact test
Incidence of Toxicities as Assessed by NCI CTCAE v. 4.0 Up to 5 years The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment
Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the First Quartile (Q1) Up to 5 years Prognostic value of urinary prostaglandin metabolites (PGE-M) levels for worse PFS for patients who had baseline urinary PGE-M above/below the first quartile (Q1, 10.09). Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the Median Quartile (Q2) Up to 5 years prognostic value of urinary prostaglandin metabolites (PGE-M) levels for worse PFS for patients who had baseline urinary PGE-M above/below the median quartile (Q2, 15.38). Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the Third Quartile (Q3) Up to 5 years Prognostic value of urinary prostaglandin metabolites (PGE-M) levels for worse PFS for patients who had baseline urinary PGE-M above/below the median quartile (Q3, 27.86). Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Trial Locations
- Locations (398)
Regional Medical Center
🇺🇸Anniston, Alabama, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
NEA Medical Clinic - East Matthews
🇺🇸Jonesboro, Arkansas, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Rebecca and John Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Camino Medical Group - Treatment Center
🇺🇸Mountain View, California, United States
Palo Alto Medical Foundation-Camino Division
🇺🇸Mountain View, California, United States
Palo Alto Medical Foundation
🇺🇸Palo Alto, California, United States
Scroll for more (388 remaining)Regional Medical Center🇺🇸Anniston, Alabama, United States