The Impact of Time-of-day-Dependent Administration of Nivolumab-Ipilimumab (ICI/ICI) Combination on Overall Survival in Adults With Advanced Kidney Cancer: A Pragmatic Multicenter, Randomized Controlled Trial.

Trial details

Who runs it

Guliz Ozgun

Trial code

NCT07338981

Record updated

1 October 2026

Original description

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:Read full original descriptionShow less

(CHRONO-RCC) Time-of-day-Dependent Administration of Dual Immune Check Point Inhibitors (ICI) in Advanced Kidney Cancer

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

Inclusion: 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).

Exclusion: Concurrent malignancy requiring active systemic therapy, unless disease-free for at least 2 years; 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; Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial; 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; 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; 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.

ClinicalTrials.gov NCT07338981