A Drug-drug Interaction Study of Capecitabine and Celecoxib in Patients With Advanced Solid Malignancies
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.
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
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.
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.
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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).
Manish R. Sharma, M.D.
University of Chicago Comprehensive Cancer Center
United States: Institutional Review Board
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|