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El impacto del horario de administración de EV/P en la tasa de respuesta objetiva en adultos con cáncer de vejiga avanzado (Chrono-EVP)

29 de septiembre de 2026 actualizado por: Guliz Ozgun

CHRONO-EVP: Administración Dependiente del Momento del Día de Enfortumab Vedotin y Pembrolizumab (EV/P) en Cáncer de Vejiga Avanzado

The goal of this clinical trial is to learn if the timing of treatments plays a role in how effective the standard-of-care drugs enfortumab vedotin and pembrolizumab (EV/P) works to treat adults with advanced bladder cancer. The trial will also learn if time-of-day reduces EV/P side-effects.

Researchers will compare EV/P given in the morning (before 11:30am) vs in the afternoon (after 1:30pm), to see if circadian rhythm effects how EV/P works to treat advanced bladder cancer.

Participants will be randomized in Arm A or Arm B to receive drugs EV/P either in the morning (Arm A) or afternoon (Arm B) as part of their standard-of-care treatment for advanced bladder cancer. Participants will:

  • Visit the clinic either in the morning (Arm A) or afternoon (Arm B) to receive EV/P treatment as part of their regular medical care for advanced bladder cancer
  • Frequency of visits will follow standard-of-care guidelines
  • Participants will be followed-up by the study team for up to 24 months.

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Estimado)

224

Fase

  • Fase 3

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.

Estudio Contacto

Ubicaciones de estudio

  • Canadá
    • British Columbia
      • Abbotsford British Columbia, British Columbia, Canadá, V2S 0C2
        • BC Cancer - Abbotsford
        • Contacto:
      • Kelowna, British Columbia, Canadá, V1Y 5L3
        • BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre)
        • Contacto:
      • Surrey, British Columbia, Canadá, V3V 1Z2
        • BC Cancer - Surrey
        • Contacto:
      • Vancouver, British Columbia, Canadá, V5Z 4E6
        • BC Cancer - Vancouver Cancer Centre
        • Contacto:
      • Victoria, British Columbia, Canadá, V8R 6V5

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:

  • Participants must meet all of the following inclusion criteria to be eligible for participation in this trial:

    1. Age 18 or older
    2. Able to provide informed consent
    3. Histologically confirmed advanced urothelial cancer
    4. Eligible for standard-of-care EV/P regimen
    5. Measurable disease per RECIST 1.1
    6. ECOG performance status 0-2
    7. Ability to adhere to scheduled infusion times (Before 11:30 a.m. or after 1:30 pm) Waivers to the inclusion criteria will NOT be allowed.

Exclusion Criteria:

  • Participants who meet any of following exclusion criteria will not be eligible for participation in this trial:

    1. Non-urothelial histology or mixed histology with predominant non-urothelial components
    2. Concurrent malignancy requiring active systemic therapy, unless disease-free for at least 2 years
    3. Inability to comply with protocol-specified infusion timing for at least the first 3 months
    4. Night shift workers
    5. Clinical evidence of new or enlarging brain metastasis or carcinomatous meningitis
    6. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
    7. Patients who have traveled across ≥2 time zones within the past 14 days prior to randomization will be excluded, due to potential disruption of circadian rhythms (jet lag), which may affect chronotherapy-related endpoints.
    8. Patients with a clinically diagnosed sleep disorder, including but not limited to insomnia, obstructive sleep apnea, restless leg syndrome, or circadian rhythm sleep-wake disorders, that is moderate to severe, untreated, or poorly controlled, will be excluded.

Waivers to the exclusion criteria will NOT be allowed.

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: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Arm A: Morning EV/P Treatment

Participants will receive standard-of-care therapy (Ev/P) administered in the morning (before 11:30am).
Droga: enfortumab vedotin and pembrolizumab (EV/P)

Participants will receive EV/P as part of their standard-of-care therapy administered either in the morning (Arm A) or afternoon (Arm B), as determined by randomization.
Comparador activo: Arm B: Afternoon EV/P Treatment

Participants will receive standard-of-care therapy (EV/P) administered in the afternoon (after 1:30pm).
Droga: enfortumab vedotin and pembrolizumab (EV/P)

Participants will receive EV/P as part of their standard-of-care therapy administered either in the morning (Arm A) or afternoon (Arm B), as determined by randomization.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Objective response rate in in time-of-day administration of EV/P treatment
Periodo de tiempo: From enrollment to end of follow-up at 24-months.

Objective response rate (ORR) will be determined by proportion of patients achieving a complete or partial response as assessed by RECIST v1.1 criteria, confirmed by central review or investigator assessment. Tumor assessments will be performed as standard of care (typically every 12 weeks), and best overall response prior to disease progression will be used for ORR determination.
From enrollment to end of follow-up at 24-months.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Assess treatment-related tolerability and toxicity differences
Periodo de tiempo: From enrollment to the end of follow-up at 24-months.

Differences in steroid use (yes/no) for the management of treatment-related toxicity, treatment interruptions (yes/no) due to treatment-related toxicity, and treatment discontinuations (yes/no) due to treatment-related toxicity will be used as surrogate safety outcomes, as comprehensive adverse event documentation is beyond the scope of this pragmatic clinical trial. The study seeks to determine whether treatment administration at a predefined time of day is associated with differences in the need for toxicity-related clinical interventions. Given that the relevant adverse events are well characterized in the existing literature, the focus of this study is on comparative safety between groups using these surrogate measures rather than on detailed characterization of individual adverse events.
From enrollment to the end of follow-up at 24-months.
Immune Profiling
Periodo de tiempo: At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment

Immune cell populations will be characterized from the blood samples at baseline (prior to treatment initiation) and at three predefined time points during therapy: 1 day after treatment initiation, 3 weeks into treatment, and 12 weeks into treatment. Cytometry by time-of-flight (CyTOF) will be used to comprehensively profile immune cell populations allowing for high-dimensional assessment of immune cell composition and activation states across treatment timing groups.
At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment
Bulk RNA sequencing (RNA-seq)
Periodo de tiempo: At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment

Bulk RNA sequencing (RNA-seq) will be performed to comprehensively characterize global gene expression profiles and to evaluate time-of-day-associated differences in immune-related transcriptional signatures. This approach will enable the identification of circadian variation in gene expression and provide insight into temporal regulation of immune pathways in response to treatment.
At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment
Cytokine and chemokine analyses
Periodo de tiempo: At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment

Plasma will be isolated for cytokine and chemokine analyses to assess systemic immune signaling and inflammatory profiles. Quantitative evaluation of circulating cytokines and chemokines will provide insight into treatment- and time-dependent changes in immune activation, inflammation, and immune regulation, complementing cellular and transcriptional immune profiling.
At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment
Evaluate Progression-Free Survival in time-of-day administration of EV/P
Periodo de tiempo: From enrollment to end of follow-up at 24-months.

Progression-free Survival (PFS) will be determined by time of randomization to radiographic progression or death from any cause, whichever occurs first.
From enrollment to end of follow-up at 24-months.
Assess Overall-Survival in time-of-day administration of EV/P
Periodo de tiempo: From enrollment to the end of follow-up at 24-months.

Overall-survival (OS) is defined as the time from randomization to death from any cause. The analysis will compare OS curves between study arms and estimate 2-year OS rates for each group.
From enrollment to the end of follow-up at 24-months.
Evaluate the Time-to-Treatment Failure in time-of-day administration of EV/P
Periodo de tiempo: From enrollment to the end of follow-up at 24-months.

Time to treatment failure (TTF) is determined by assessing time from treatment initiation to treatment discontinuation for any reason, including disease progression, unacceptable toxicity, patient withdrawal, or death, capturing both treatment efficacy and tolerability.
From enrollment to the end of follow-up at 24-months.
Assess quantitative changes in ctDNA Kinetics of time-of-day administration of EV/P
Periodo de tiempo: Baseline, 3 weeks, and 12-weeks.

Quantitative changes in circulating tumour DNA (ctDNA) levels will be collected and measured at baseline, post-cycle 1 (~3 weeks), and at post-cycle 4 (~12 weeks) at first radiographic assessment, with correlation to response and survival outcomes.
Baseline, 3 weeks, and 12-weeks.
Circulating Tumor DNA (ctDNA) Analyses
Periodo de tiempo: At 3 time points: Baseline, 3 weeks into treatment and 12 weeks into treatment

Circulating tumor DNA (ctDNA) analyses will be performed on plasma samples collected at baseline (prior to treatment initiation), 3 weeks into treatment, and 12 weeks into treatment. ctDNA dynamics will be evaluated to assess molecular response to therapy, including changes in ctDNA levels and ctDNA clearance rates over time. Comparisons will be made between treatment administration at different times of day to determine whether timing of therapy is associated with differences in ctDNA kinetics, clearance rates, and early molecular response.
At 3 time points: Baseline, 3 weeks into treatment and 12 weeks into treatment

Colaboradores e Investigadores

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

Patrocinador

Guliz Ozgun

Colaboradores

British Columbia Cancer Agency

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.

Publicaciones Generales

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 (Estimado)

1 de noviembre de 2026

Finalización primaria (Estimado)

1 de diciembre de 2030

Finalización del estudio (Estimado)

1 de diciembre de 2032

Fechas de registro del estudio

Enviado por primera vez

8 de diciembre de 2025

Primero enviado que cumplió con los criterios de control de calidad

7 de enero de 2026

Publicado por primera vez (Actual)

16 de enero de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

1 de octubre de 2026

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

29 de septiembre de 2026

Última verificación

1 de septiembre de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • Chrono-EVP

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

INDECISO

Información sobre medicamentos y dispositivos, documentos del estudio

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

No

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

No

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