CHRONO-EVP: Time-of-day Dependent Administration of Enfortumab Vedotin and Pembrolizumab (EV/P) in Advanced Bladder Cancer
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 224
- 试验地点
- 5
- 主要终点
- Objective response rate in in time-of-day administration of EV/P treatment
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following inclusion criteria to be eligible for participation in this trial:
- •Age 18 or older
- •Able to provide informed consent
- •Histologically confirmed advanced urothelial cancer
- •Eligible for standard-of-care EV/P regimen
- •Measurable disease per RECIST 1.1
- •ECOG performance status 0-2
- •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.
排除标准
- •Participants who meet any of following exclusion criteria will not be eligible for participation in this trial:
- •Non-urothelial histology or mixed histology with predominant non-urothelial components
- •Concurrent malignancy requiring active systemic therapy, unless disease-free for at least 2 years
- •Inability to comply with protocol-specified infusion timing for at least the first 3 months
- •Night shift workers
- •Clinical evidence of new or enlarging brain metastasis or carcinomatous meningitis
- •Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
- •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.
- •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.
研究组 & 干预措施
Arm A: Morning EV/P Treatment
Participants will receive standard-of-care therapy (Ev/P) administered in the morning (before 11:30am).
干预措施: enfortumab vedotin and pembrolizumab (EV/P) (Drug)
Arm B: Afternoon EV/P Treatment
Participants will receive standard-of-care therapy (EV/P) administered in the afternoon (after 1:30pm).
干预措施: enfortumab vedotin and pembrolizumab (EV/P) (Drug)
结局指标
主要结局
Objective response rate in in time-of-day administration of EV/P treatment
时间窗: 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.
次要结局
- Evaluate Progression-Free Survival in time-of-day administration of EV/P(From enrollment to end of follow-up at 24-months.)
- Assess Overall-Survival in time-of-day administration of EV/P(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(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(Baseline, 3 weeks, and 12-weeks.)
- Assess treatment-related tolerability and toxicity differences(From enrollment to the end of follow-up at 24-months.)
- Immune Profiling(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)(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(At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment)
- Circulating Tumor DNA (ctDNA) Analyses(At 3 time points: Baseline, 3 weeks into treatment and 12 weeks into treatment)
研究者
Guliz Ozgun
Medical Oncologist, Principal Investigator
British Columbia Cancer Agency