This clinical trial studies capecitabine and celecoxib in treating patients with solid malignancies that are metastatic or cannot be removed by surgery. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving capecitabine and celecoxib together may be an effective treatment for solid malignancies.
PRIMARY OBJECTIVES: I. To compare steady state pharmacokinetics (PK) (primarily minimum concentration \[Cmin\], maximum concentration \[Cmax\], and area under the curve \[AUC\]) of celecoxib on day 7 of monotherapy versus on day 14 of concomitant administration with capecitabine. SECONDARY OBJECTIVES: I. To develop a celecoxib PK drug interaction model using longitudinal data and determine whether the results are concordant with results from the primary objective. II. To assess the impact of known cytochrome P450 2C9 (CYP2C9) pharmacogenetic variants with reduced enzyme activity (CYP2C9\*2 and \*3) on the between subject variability in celecoxib PK. III. To assess tumor response by the Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) and explore whether there is any correlation between celecoxib PK and response. IV. To assess toxicity by the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and explore whether there is any correlation between celecoxib PK and toxicities related to either celecoxib or capecitabine. OUTLINE: Patients receive celecoxib orally (PO) twice daily (BID) for 7 days (course 0) and then on days 1-21 of course 1 and all subsequent courses. Patients also receive capecitabine PO BID on days 1-14 beginning in course 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Given PO
Given PO
Correlative studies
Correlative studies
Correlative studies
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
AUC of Celecoxib on Combination Therapy (Day 14) and AUC of Celecoxib on Celecoxib Monotherapy(Day 7)
These parameters will be estimated for each subject under each treatment condition. The mean ratios (combination therapy/celecoxib monotherapy) will then be estimated together with 90% confidence intervals (CI).
Time frame: Day 7 and 14 post treatment
CYP2C9 Genotype
Polymorphisms \*2 and \*3 will be genotyped and analyzed for their impact on celecoxib AUC using analysis of variance (ANOVA), controlling for gender, age, and other covariates.
Time frame: one week
Response Rate
Logistic regression analysis will be performed to describe the relationship (if any) between celecoxib AUC and response rate.
Time frame: Up to 2 years
Drug-related Toxicities
Ordinal logistic regression modeling will be used to explore the relationship between celecoxib AUC and toxicity.
Time frame: Up to six months
PK Drug Interaction Model
NONMEM software will be used to develop a model describing the drug interaction between capecitabine and celecoxib using PK data collected during the first four weeks of the study.
Time frame: 4 weeks
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