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

30. april 2018 oppdatert av: 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.

Studieoversikt

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

21

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

    • Illinois
      • Chicago, Illinois, Forente stater, 60637-1470
        • University of Chicago Comprehensive Cancer Center

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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 studier
Korrelative studier
Andre navn:
  • farmakologiske studier
Gitt PO
Andre navn:
  • Xeloda
  • KAPPE
  • Ro 09-1978/000
Gitt PO
Andre navn:
  • Celebrex
  • SC-58635
Korrelative studier
Andre navn:
  • Farmakogenomisk studie

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Samarbeidspartnere

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

29. august 2012

Primær fullføring (Faktiske)

10. februar 2016

Studiet fullført (Faktiske)

10. februar 2016

Datoer for studieregistrering

Først innsendt

8. oktober 2012

Først innsendt som oppfylte QC-kriteriene

10. oktober 2012

Først lagt ut (Anslag)

12. oktober 2012

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

30. mai 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

30. april 2018

Sist bekreftet

1. april 2018

Mer informasjon

Begreper knyttet til denne studien

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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