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
Age 18 or older
Able to provide informed consent
Histologically confirmed advanced clear cell kidney cancer
Eligible for standard-of-care nivolumab/ipilimumab regimen
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
Parallel
Nivolumab & Ipilimumab
DrugParticipants will receive ICI/ICI as part of their standard-of-care therapy administered in the morning before 11:30am (Arm A) , as determined by randomization.
Nivolumab + Ipilimumab
DrugParticipants will receive ICI/ICI as part of their standard-of-care therapy administered in the afternoon after 1:30pm (Arm B) , as determined by randomization.
Assess Overall-Survival in time-of-day administration of ICI/ICI treatment
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.
Determine Objective Response Rate in time-of-day administration of ICI/ICI treatment
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 or investigator review. 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.
Evaluate Progression-Free Survival in time-of-day administration of ICI/ICI treatment
Progression-free Survival (PFS) will be determined by time of randomization to disease progression or death from any cause.
Determine the Time-to-Treatment Failure in time-of-day administration of ICI/ICI treatment
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.
Assess treatment-related tolerability and toxicity differences
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.
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Guliz Ozgun
Lead sponsor
British Columbia Cancer Agency
Sponsor institution
British Columbia Cancer Agency
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
