- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT01705106
Capecitabine and Celecoxib in Patients With Solid Cancers That Have Been Previously Treated With Standard Therapies
A Drug-drug Interaction Study of Capecitabine and Celecoxib in Patients With Advanced Solid Malignancies
Studienübersicht
Status
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Kontakte und Standorte
Studienorte
-
-
Illinois
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Chicago, Illinois, Vereinigte Staaten, 60637-1470
- University of Chicago Comprehensive Cancer Center
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: 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 Studien
Korrelative Studien
Andere Namen:
PO gegeben
Andere Namen:
Gegeben PO
Andere Namen:
Korrelative Studien
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
AUC of Celecoxib on Combination Therapy (Day 14) and AUC of Celecoxib on Celecoxib Monotherapy(Day 7)
Zeitfenster: 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).
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Day 7 and 14 post treatment
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
CYP2C9 Genotype
Zeitfenster: 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.
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one week
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Response Rate
Zeitfenster: Up to 2 years
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Logistic regression analysis will be performed to describe the relationship (if any) between celecoxib AUC and response rate.
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Up to 2 years
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Drug-related Toxicities
Zeitfenster: Up to six months
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Ordinal logistic regression modeling will be used to explore the relationship between celecoxib AUC and toxicity.
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Up to six months
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PK Drug Interaction Model
Zeitfenster: 4 weeks
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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.
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4 weeks
|
Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Ermittler
- Hauptermittler: Manish R. Sharma, M.D., University of Chicago Comprehensive Cancer Center
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Agenten des peripheren Nervensystems
- Enzym-Inhibitoren
- Analgetika
- Agenten des sensorischen Systems
- Entzündungshemmende Mittel, nichtsteroidal
- Analgetika, nicht narkotisch
- Entzündungshemmende Mittel
- Antirheumatika
- Cyclooxygenase-Inhibitoren
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Cyclooxygenase-2-Inhibitoren
- Capecitabin
- Celecoxib
Andere Studien-ID-Nummern
- 12-1318
- NCI-2012-01704 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Produkt, das in den USA hergestellt und aus den USA exportiert wird
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