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

30. april 2018 opdateret af: University of Chicago

A Drug-drug Interaction Study of Capecitabine and Celecoxib in Patients With Advanced Solid Malignancies

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.

Studieoversigt

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

21

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Illinois
      • Chicago, Illinois, Forenede Stater, 60637-1470
        • University of Chicago Comprehensive Cancer Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Korrelative undersøgelser
Korrelative undersøgelser
Andre navne:
  • farmakologiske undersøgelser
Givet PO
Andre navne:
  • Xeloda
  • KAP
  • Ro 09-1978/000
Givet PO
Andre navne:
  • Celebrex
  • SC-58635
Korrelative undersøgelser
Andre navne:
  • Farmakogenomisk undersøgelse

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
AUC of Celecoxib on Combination Therapy (Day 14) and AUC of Celecoxib on Celecoxib Monotherapy(Day 7)
Tidsramme: Day 7 and 14 post treatment
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).
Day 7 and 14 post treatment

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
CYP2C9 Genotype
Tidsramme: one week
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.
one week
Response Rate
Tidsramme: Up to 2 years
Logistic regression analysis will be performed to describe the relationship (if any) between celecoxib AUC and response rate.
Up to 2 years
Drug-related Toxicities
Tidsramme: Up to six months
Ordinal logistic regression modeling will be used to explore the relationship between celecoxib AUC and toxicity.
Up to six months
PK Drug Interaction Model
Tidsramme: 4 weeks
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.
4 weeks

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Samarbejdspartnere

Efterforskere

  • Ledende efterforsker: Manish R. Sharma, M.D., University of Chicago Comprehensive Cancer Center

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

29. august 2012

Primær færdiggørelse (Faktiske)

10. februar 2016

Studieafslutning (Faktiske)

10. februar 2016

Datoer for studieregistrering

Først indsendt

8. oktober 2012

Først indsendt, der opfyldte QC-kriterier

10. oktober 2012

Først opslået (Skøn)

12. oktober 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

30. maj 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

30. april 2018

Sidst verificeret

1. april 2018

Mere information

Begreber relateret til denne undersøgelse

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

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