(CHRONO-RCC) Time-of-day-Dependent Administration of Dual Immune Check Point Inhibitors (ICI) in Advanced Kidney Cancer
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 142
- 试验地点
- 1
- 主要终点
- Assess Overall-Survival in time-of-day administration of ICI/ICI 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 nivolumab/ipilimumab (ICI/ICI) works to treat adults with advanced kidney cancer. The trial will also learn if time-of-day reduces ICI/ICI side-effects. Researchers will compare ICI/ICI given in the morning (before 11:30am) vs in the afternoon (after 1:30pm), to see if circadian rhythm effects how ICI/ICI works to treat advanced kidney cancer. Participants will be randomized in Arm A or Arm B to receive drugs ICI/ICI either in the morning (Arm A) or afternoon (Arm B) as part of their standard-of-care treatment for advanced kidney cancer. Participants will:
- Visit the clinic either in the morning (Arm A) or afternoon (Arm B) to receive ICI/ICI treatment as part of their regular medical care for advanced kidney cancer
- Frequency of visits will follow standard-of-care guidelines
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 criteria to be eligible for participation in this trial. Waivers to the inclusion criteria will NOT be allowed.
- •Age 18 or older
- •Able to provide informed consent
- •Histologically confirmed advanced clear cell kidney cancer
- •Eligible for standard-of-care nivolumab/ipilimumab 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)
排除标准
- •Participants are excluded from the trial if any of the following criteria apply. Waivers to the exclusion criteria will NOT be allowed.
- •Non-clear cell RCC histology
- •Concurrent malignancy requiring active systemic therapy, unless disease-free for at least 2 years
- •Inability to comply with protocol-specified infusion timing for the first 4 cycles
- •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.
研究组 & 干预措施
Arm A: Morning ICI/ICI Treatment
Participants will receive standard-of-care therapy (ICI/ICI) administered in the morning (before 11:30am).
干预措施: Nivolumab & Ipilimumab (Drug)
Arm B: Afternoon ICI/ICI Treatment
Participants will receive standard-of-care therapy (ICI/ICI) administered in the afternoon (after 1:30pm).
干预措施: Nivolumab + Ipilimumab (Drug)
结局指标
主要结局
Assess Overall-Survival in time-of-day administration of ICI/ICI treatment
时间窗: From enrollment to the end of follow-up at 24 months.
To assess overall survival (OS) in patients treated with time-of day dependent administration of nivolumab-ipilimumab (ICI/ICI) standard-of-care therapy in advanced kidney cancer. OS is defined as the time from randomization to death from any cause. The primary analysis will compare OS curves between study arms and estimate 2-year OS rates for each group.
次要结局
- Determine Objective Response Rate in time-of-day administration of ICI/ICI treatment(From enrollment to the end of follow-up at 24-months.)
- Evaluate Progression-Free Survival in time-of-day administration of ICI/ICI treatment(From enrollment to the end of follow-up at 24-months.)
- Determine the Time-to-Treatment Failure in time-of-day administration of ICI/ICI treatment(From enrollment to the end of follow-up at 24-months.)
- 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)
研究者
Guliz Ozgun
Medical Oncologist, Principal Investigator
British Columbia Cancer Agency