- ICH GCP
- Registre américain des essais cliniques
- Essai clinique 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
Aperçu de l'étude
Statut
Les conditions
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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Illinois
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Chicago, Illinois, États-Unis, 60637-1470
- University of Chicago Comprehensive Cancer Center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: 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.
|
Études corrélatives
Études corrélatives
Autres noms:
Bon de commande donné
Autres noms:
Bon de commande donné
Autres noms:
Études corrélatives
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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AUC of Celecoxib on Combination Therapy (Day 14) and AUC of Celecoxib on Celecoxib Monotherapy(Day 7)
Délai: Day 7 and 14 post treatment
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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
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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CYP2C9 Genotype
Délai: one week
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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
Délai: 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
Délai: 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
Délai: 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
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Manish R. Sharma, M.D., University of Chicago Comprehensive Cancer Center
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents du système nerveux périphérique
- Inhibiteurs d'enzymes
- Analgésiques
- Agents du système sensoriel
- Agents anti-inflammatoires non stéroïdiens
- Analgésiques, non narcotiques
- Agents anti-inflammatoires
- Agents antirhumatismaux
- Inhibiteurs de la cyclooxygénase
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Inhibiteurs de la cyclooxygénase 2
- Capécitabine
- Célécoxib
Autres numéros d'identification d'étude
- 12-1318
- NCI-2012-01704 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
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