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

NCT ID: NCT01705106

Last Updated: 2018-05-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-29
• Study Completion Date: 2016-02-10

Brief Summary

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.

Detailed Description

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (capecitabine, celecoxib)

Patients receive celecoxib PO 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.

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

Given PO

celecoxib

Intervention Type: DRUG

Given PO

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacogenomic studies

Intervention Type: OTHER

Correlative studies

Interventions

capecitabine

Given PO

Intervention Type: DRUG

celecoxib

Given PO

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacogenomic studies

Correlative studies

Intervention Type: OTHER

Other Intervention Names

CAPE; Ro 09-1978/000; Xeloda; Celebrex; SC-58635; pharmacological studies; Pharmacogenomic Study

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manish R. Sharma, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Countries

United States

References

Wood K, Byron E, Janisch L, Salgia R, Sharma MR. Capecitabine and Celecoxib as a Promising Therapy for Thymic Neoplasms. Am J Clin Oncol. 2018 Oct;41(10):963-966. doi: 10.1097/COC.0000000000000400.

Reference Type: DERIVED

PMID: 28654574 (View on PubMed)

Other Identifiers

NCI-2012-01704

Identifier Type: REGISTRY

Identifier Source: secondary_id

12-1318

Identifier Type: -

Identifier Source: org_study_id