Capecitabine and Celecoxib in Patients With Solid Cancers That Have Been Previously Treated With Standard Therapies

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.

Inclusion Criteria:

- Histologically or cytologically confirmed solid tumor that is metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective

OR

Histologically or cytologically confirmed solid tumor for which single agent capecitabine
is an appropriate treatment option.

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1

- Life expectancy > 3 months

- Absolute neutrophil count (ANC) >= l500/ul

- Hemoglobin >= 9g/dL

- Platelets >= 100,000/ul

- Creatinine within institutional normal limits or glomerular filtration rate >= 50
mL/min/1.73 m^2 by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI)
equation

- Total bilirubin < 1.5 x upper limit of normal

- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate
transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver
metastases OR SGOT and SGPT < 5 x upper limit of normal for patients with liver
metastases

- Measurable or non-measurable disease will be allowed

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation, up until 30 days after final study treatment;
should a woman become pregnant or suspect that she is pregnant while participating in
this study, she should inform her treating physician immediately

- Patients taking substrates of CYP2C9 should be encouraged to switch to alternative
drugs whenever possible, given the potential for drug-drug interactions with the study
drugs

- Signed informed consent

Exclusion Criteria:

- Prior treatment with capecitabine and/or celecoxib is allowed; however, patients with
a documented history (at the time of enrollment) of >= grade 3 toxicities with
capecitabine or celecoxib are excluded

- Patients taking any of the following drugs are excluded: inducers or inhibitors of
CYP2C9, warfarin, aspirin, corticosteroids, or non-steroidal anti-inflammatory drugs
(NSAIDs)

- History of myocardial infarction or stroke within the last 6 months, or history of
uncontrolled cardiovascular or cerebrovascular disease; a 12-lead electrocardiogram
(ECG) will be performed during the screening period

- History of perforation or bleeding related to peptic ulcer disease

- History of hypersensitivity or allergy to study drugs, aspirin, sulfonamides, or
NSAIDs

- Known poor metabolizers of CYP2C9 substrates

- Known deficiency of dihydropyrimidine dehydrogenase (DPD)

- Patients who have had chemotherapy, immunotherapy, or investigational anti-cancer
therapy within 4 weeks of starting study drug, or radiotherapy within 14 days of
starting study drug, or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier

- Patients may not be receiving any other investigational agents or any concomitant
antineoplastic therapy, with the exception of androgen ablating agents (for patients
with prior prostate cancer)

- Serious underlying medical or psychiatric illnesses that would, in the opinion of the
treating physician, substantially increase the risk for complications related to
treatment; similarly, any unstable medical condition that in the opinion of the
treating physician or study investigators, would interfere with determination of the
study objectives

- Pregnancy or breastfeeding

- Major surgery within 4 weeks