Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

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

30 de abril de 2018 actualizado por: 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.

Descripción general del estudio

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Actual)

21

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Illinois
      • Chicago, Illinois, Estados Unidos, 60637-1470
        • University of Chicago Comprehensive Cancer Center

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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 de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
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.
Estudios correlativos
Estudios correlativos
Otros nombres:
  • estudios farmacológicos
Orden de compra dada
Otros nombres:
  • Xeloda
  • CAPA
  • Ro 09-1978/000
Orden de compra dada
Otros nombres:
  • Celebrex
  • SC-58635
Estudios correlativos
Otros nombres:
  • Estudio Farmacogenómico

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
AUC of Celecoxib on Combination Therapy (Day 14) and AUC of Celecoxib on Celecoxib Monotherapy(Day 7)
Periodo de tiempo: 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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
CYP2C9 Genotype
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Investigadores

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

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

29 de agosto de 2012

Finalización primaria (Actual)

10 de febrero de 2016

Finalización del estudio (Actual)

10 de febrero de 2016

Fechas de registro del estudio

Enviado por primera vez

8 de octubre de 2012

Primero enviado que cumplió con los criterios de control de calidad

10 de octubre de 2012

Publicado por primera vez (Estimar)

12 de octubre de 2012

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

30 de mayo de 2018

Última actualización enviada que cumplió con los criterios de control de calidad

30 de abril de 2018

Última verificación

1 de abril de 2018

Más información

Términos relacionados con este estudio

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

producto fabricado y exportado desde los EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Suscribir