Advanced Kidney CancerPhase 3NCT07338981
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.
A Phase 3 study testing Nivolumab & Ipilimumab and Nivolumab + Ipilimumab in people with Advanced Kidney Cancer, run by Guliz Ozgun at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Kidney Cancer
- What is being tested?
- Nivolumab & Ipilimumab and Nivolumab + Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2027to Dec 2033
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
BC Cancer - Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: (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
- Conditions
- Advanced Kidney Cancer
- Being tested
- Nivolumab & Ipilimumab, Nivolumab + Ipilimumab
- Keywords
- Chronoimmunotherapy, Time-of-day administration, Chronotherapy, Circadian rhythm, Advanced kidney cancer, Nivolumab/Ipilimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab & IpilimumabDrug
Also called ICI/ICI
Participants 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 + IpilimumabDrug
Participants 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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Morning ICI/ICI Treatment | Active comparator | Participants will receive standard-of-care therapy (ICI/ICI) administered in the morning (before 11:30am). Receives: Drug: Nivolumab & Ipilimumab |
| Arm B: Afternoon ICI/ICI Treatment | Active comparator | Participants will receive standard-of-care therapy (ICI/ICI) administered in the afternoon (after 1:30pm). Receives: Drug: Nivolumab + Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrollment to the end of follow-up at 24 months.
Secondary outcomes (7)
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.
Measured: From enrollment to the end of follow-up at 24-months.
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.
Measured: 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
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.
Measured: From enrollment to the end of follow-up at 24-months.
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.
Measured: From enrollment to the end of follow-up at 24-months.
Immune Profiling
Immune cell populations will be characterized from the blood samples at baseline (prior to treatment initiation) and at three predefined time points during therapy: 1 day after treatment initiation, 3 weeks into treatment, and 12 weeks into treatment. Cytometry by time-of-flight (CyTOF) will be used to comprehensively profile immune cell populations allowing for high-dimensional assessment of immune cell composition and activation states across treatment timing groups.
Measured: 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)
Bulk RNA sequencing (RNA-seq) will be performed to comprehensively characterize global gene expression profiles and to evaluate time-of-day-associated differences in immune-related transcriptional signatures. This approach will enable the identification of circadian variation in gene expression and provide insight into temporal regulation of immune pathways in response to treatment.
Measured: 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
Plasma will be isolated for cytokine and chemokine analyses to assess systemic immune signaling and inflammatory profiles. Quantitative evaluation of circulating cytokines and chemokines will provide insight into treatment- and time-dependent changes in immune activation, inflammation, and immune regulation, complementing cellular and transcriptional immune profiling.
Measured: At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2026
- Study startFeb 2027 (estimated)
- Primary completionDec 2031 (estimated)
- Study completionDec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Advanced Kidney CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is a randomized, controlled trial designed to evaluate the effects of timing of standard-of-care (SOC) treatment administration on patient outcomes. Participants will be randomly assigned to receive SOC nivolumab/ipilimumab either in the morning or in the afternoon, with no additional interventions planned. Patients will be scheduled for treatments at the same time for the first four cycles, with a ±1 hour flexibility, to minimize the impact of timing as a confounding factor in the analyses. The trial is open-label and not blinded due to the nature of the intervention (timing of treatment).
- Masking
- None (open label)
- Enrolment
- 142 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guliz Ozgun
- Sponsor type
- University, hospital or other
- Collaborators
- British Columbia Cancer Agency
- Responsible party
- Sponsor-investigator, Guliz Ozgun, British Columbia Cancer Agency
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07338981
- Sponsor's protocol ID
- Chrono-RCC
- Status last verified
- Sep 2026
- First submitted
- 5 Dec 2025
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Wang C, Zeng Q, Gul ZM, Wang S, Pick R, Cheng P, Bill R, Wu Y, Naulaerts S, Barnoud C, Hsueh PC, Moller SH, Cenerenti M, Sun M, Su Z, Jemelin S, Petrenko V, Dibner C, Hugues S, Jandus C, Li Z, Michielin O, Ho PC, Garg AD, Simonetta F, Pittet MJ, Scheiermann C. Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy. Cell. 2024 May 23;187(11):2690-2702.e17. doi: 10.1016/j.cell.2024.04.015. Epub 2024 May 8.
PubMed 38723627Fortin BM, Pfeiffer SM, Insua-Rodriguez J, Alshetaiwi H, Moshensky A, Song WA, Mahieu AL, Chun SK, Lewis AN, Hsu A, Adam I, Eng OS, Pannunzio NR, Seldin MM, Marazzi I, Marangoni F, Lawson DA, Kessenbrock K, Masri S. Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade. Nat Immunol. 2024 Jul;25(7):1257-1269. doi: 10.1038/s41590-024-01859-0. Epub 2024 May 28.
PubMed 38806707Lee Y. Roles of circadian clocks in cancer pathogenesis and treatment. Exp Mol Med. 2021 Oct;53(10):1529-1538. doi: 10.1038/s12276-021-00681-0. Epub 2021 Oct 7.
PubMed 34615982Karaboue A, Innominato PF, Wreglesworth NI, Duchemann B, Adam R, Levi FA. Why does circadian timing of administration matter for immune checkpoint inhibitors' efficacy? Br J Cancer. 2024 Sep;131(5):783-796. doi: 10.1038/s41416-024-02704-9. Epub 2024 Jun 4.
PubMed 38834742Dizman N, Govindarajan A, Zengin ZB, Meza L, Tripathi N, Sayegh N, Castro DV, Chan EH, Lee KO, Prajapati S, Feng M, Loo V, Pace M, O'Brien S, Bailey E, Barragan-Carrillo R, Chehrazi-Raffle A, Hsu J, Li X, Agarwal N, Pal SK. Association Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma. Clin Genitourin Cancer. 2023 Oct;21(5):530-536. doi: 10.1016/j.clgc.2023.06.004. Epub 2023 Jun 25.
PubMed 37495481Patel JS, Woo Y, Draper A, Jansen CS, Carlisle JW, Innominato PF, Levi FA, Dhabaan L, Master VA, Bilen MA, Khan MK, Lowe MC, Kissick H, Buchwald ZS, Qian DC. Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis. J Immunother Cancer. 2024 Mar 26;12(3):e008011. doi: 10.1136/jitc-2023-008011.
PubMed 38531662Giacchetti S, Bjarnason G, Garufi C, Genet D, Iacobelli S, Tampellini M, Smaaland R, Focan C, Coudert B, Humblet Y, Canon JL, Adenis A, Lo Re G, Carvalho C, Schueller J, Anciaux N, Lentz MA, Baron B, Gorlia T, Levi F; European Organisation for Research and Treatment of Cancer Chronotherapy Group. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol. 2006 Aug 1;24(22):3562-9. doi: 10.1200/JCO.2006.06.1440.
PubMed 16877722Levi F, Okyar A, Dulong S, Innominato PF, Clairambault J. Circadian timing in cancer treatments. Annu Rev Pharmacol Toxicol. 2010;50:377-421. doi: 10.1146/annurev.pharmtox.48.113006.094626.
PubMed 20055686Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.
PubMed 29562145
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (CHRONO-RCC) Time-of-day-Dependent Administration of Dual Immune Check Point Inhibitors (ICI) in Advanced Kidney Cancer
- ClinicalTrials.gov ID
- NCT07338981
- Acronym / sponsor ID
- Chrono-RCC
- Conditions
- Advanced Kidney Cancer
- Keywords
- Chronoimmunotherapy, Time-of-day administration, Chronotherapy, Circadian rhythm, Advanced kidney cancer, Nivolumab/Ipilimumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 142 participants (estimated)
- Lead sponsor
- Guliz OzgunUniversity, hospital or other
- Collaborators
- British Columbia Cancer Agency
- Study start
- Feb 2027 (estimated)
- Primary completion
- Dec 2031 (estimated)
- Study completion
- Dec 2033 (estimated)
- First posted
- 14 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This study is a randomized, controlled trial designed to evaluate the effects of timing of standard-of-care (SOC) treatment administration on patient outcomes. Participants will be randomly assigned to receive SOC nivolumab/ipilimumab either in the morning or in the afternoon, with no additional interventions planned. Patients will be scheduled for treatments at the same time for the first four cycles, with a ±1 hour flexibility, to minimize the impact of timing as a confounding factor in the analyses. The trial is open-label and not blinded due to the nature of the intervention (timing of treatment).
| Arm | Type | Receives |
|---|---|---|
| Arm A: Morning ICI/ICI Treatment | Active comparator | Drug: Nivolumab & IpilimumabParticipants will receive standard-of-care therapy (ICI/ICI) administered in the morning (before 11:30am). |
| Arm B: Afternoon ICI/ICI Treatment | Active comparator | Drug: Nivolumab + IpilimumabParticipants will receive standard-of-care therapy (ICI/ICI) administered in the afternoon (after 1:30pm). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab & IpilimumabAlso: ICI/ICIParticipants 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. | Drug | Arm A: Morning ICI/ICI Treatment |
| Nivolumab + IpilimumabParticipants 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. | Drug | Arm B: Afternoon ICI/ICI Treatment |
Primary outcome
Assess Overall-Survival in time-of-day administration of ICI/ICI treatment
Time frame: 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.
7 secondary outcomes
Determine Objective Response Rate in time-of-day administration of ICI/ICI treatment
Time frame: From enrollment to the end of follow-up at 24-months.
Evaluate Progression-Free Survival in time-of-day administration of ICI/ICI treatment
Time frame: 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
Time frame: From enrollment to the end of follow-up at 24-months.
Assess treatment-related tolerability and toxicity differences
Time frame: From enrollment to the end of follow-up at 24-months.
Immune Profiling
Time frame: 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)
Time frame: 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
Time frame: At 4 time points: Baseline, 1-day post first cycle of treatment, 3 weeks into treatment and 12 weeks into treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- Background: PubMed 38723627Wang C, Zeng Q, Gul ZM, Wang S, Pick R, Cheng P, Bill R, Wu Y, Naulaerts S, Barnoud C, Hsueh PC, Moller SH, Cenerenti M, Sun M, Su Z, Jemelin S, Petrenko V, Dibner C, Hugues S, Jandus C, Li Z, Michielin O, Ho PC, Garg AD, Simonetta F, Pittet MJ, Scheiermann C. Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy. Cell. 2024 May 23;187(11):2690-2702.e17. doi: 10.1016/j.cell.2024.04.015. Epub 2024 May 8.
- Background: PubMed 38806707Fortin BM, Pfeiffer SM, Insua-Rodriguez J, Alshetaiwi H, Moshensky A, Song WA, Mahieu AL, Chun SK, Lewis AN, Hsu A, Adam I, Eng OS, Pannunzio NR, Seldin MM, Marazzi I, Marangoni F, Lawson DA, Kessenbrock K, Masri S. Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade. Nat Immunol. 2024 Jul;25(7):1257-1269. doi: 10.1038/s41590-024-01859-0. Epub 2024 May 28.
- Background: PubMed 34615982Lee Y. Roles of circadian clocks in cancer pathogenesis and treatment. Exp Mol Med. 2021 Oct;53(10):1529-1538. doi: 10.1038/s12276-021-00681-0. Epub 2021 Oct 7.
- Background: PubMed 38834742Karaboue A, Innominato PF, Wreglesworth NI, Duchemann B, Adam R, Levi FA. Why does circadian timing of administration matter for immune checkpoint inhibitors' efficacy? Br J Cancer. 2024 Sep;131(5):783-796. doi: 10.1038/s41416-024-02704-9. Epub 2024 Jun 4.
- Background: PubMed 37495481Dizman N, Govindarajan A, Zengin ZB, Meza L, Tripathi N, Sayegh N, Castro DV, Chan EH, Lee KO, Prajapati S, Feng M, Loo V, Pace M, O'Brien S, Bailey E, Barragan-Carrillo R, Chehrazi-Raffle A, Hsu J, Li X, Agarwal N, Pal SK. Association Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma. Clin Genitourin Cancer. 2023 Oct;21(5):530-536. doi: 10.1016/j.clgc.2023.06.004. Epub 2023 Jun 25.
- Background: PubMed 38531662Patel JS, Woo Y, Draper A, Jansen CS, Carlisle JW, Innominato PF, Levi FA, Dhabaan L, Master VA, Bilen MA, Khan MK, Lowe MC, Kissick H, Buchwald ZS, Qian DC. Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis. J Immunother Cancer. 2024 Mar 26;12(3):e008011. doi: 10.1136/jitc-2023-008011.
- Background: PubMed 16877722Giacchetti S, Bjarnason G, Garufi C, Genet D, Iacobelli S, Tampellini M, Smaaland R, Focan C, Coudert B, Humblet Y, Canon JL, Adenis A, Lo Re G, Carvalho C, Schueller J, Anciaux N, Lentz MA, Baron B, Gorlia T, Levi F; European Organisation for Research and Treatment of Cancer Chronotherapy Group. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol. 2006 Aug 1;24(22):3562-9. doi: 10.1200/JCO.2006.06.1440.
- Background: PubMed 20055686Levi F, Okyar A, Dulong S, Innominato PF, Clairambault J. Circadian timing in cancer treatments. Annu Rev Pharmacol Toxicol. 2010;50:377-421. doi: 10.1146/annurev.pharmtox.48.113006.094626.
- Background: PubMed 29562145Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nivolumab & Ipilimumab and Nivolumab + Ipilimumab in people with Advanced Kidney Cancer, run by Guliz Ozgun at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr. Guliz Ozgun, MD (604-877-6000 ext. 676213, guliz.ozgun@bccancer.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess Overall-Survival in time-of-day administration of ICI/ICI treatment (time frame: From enrollment to the end of follow-up at 24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07338981, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.