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.

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 Criteria: 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. 1. Age 18 or older 2. Able to provide informed consent 3. Histologically confirmed advanced clear cell kidney cancer 4. Eligible for standard-of-care nivolumab/ipilimumab 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) Exclusion Criteria: Participants are excluded from the trial if any of the following criteria apply. Waivers to the exclusion criteria will NOT be allowed. 1. Non-clear cell RCC histology 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 the first 4 cycles 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.