Advanced Bladder CancerPhase 3Chrono-EVPNCT07346053
The Impact of Time-of-day Administration of EV/P on Objective Response Rate in Adults With Advanced Bladder Cancer
A Phase 3 study testing enfortumab vedotin and pembrolizumab (EV/P) in people with Advanced Bladder Cancer, run by Guliz Ozgun at 5 sites 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 enfortumab vedotin and pembrolizumab (EV/P) works to treat adults with advanced bladder cancer. The trial will also learn if time-of-day reduces EV/P side-effects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Bladder Cancer
- What is being tested?
- enfortumab vedotin and pembrolizumab (EV/P)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 5 sitesCanada
- Study dates
- Nov 2026to Dec 2032
- 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 inclusion criteria to be eligible for participation in this trial:
- Age 18 or older
- Able to provide informed consent
- Histologically confirmed advanced urothelial cancer
- Eligible for standard-of-care EV/P 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) Waivers to the inclusion criteria will NOT be allowed.
Who cannot join
- Participants who meet any of following exclusion criteria will not be eligible for participation in this trial:
- Non-urothelial histology or mixed histology with predominant non-urothelial components
- Concurrent malignancy requiring active systemic therapy, unless disease-free for at least 2 years
- Inability to comply with protocol-specified infusion timing for at least the first 3 months
- Night shift workers
- Clinical evidence of new or enlarging brain metastasis or carcinomatous meningitis
Show all 10Show 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.
- Waivers to the exclusion criteria will NOT be allowed.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Canada5 sites
BC Cancer - Abbotsford
Abbotsford British Columbia, British Columbia, V2S 0C2
Dr. Muhammad Zulfiqar, MD, (604) 851-4710, MZulfiqar@bccancer.bc.ca
BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre)
Kelowna, British Columbia, V1Y 5L3
Dr. Daygen Finch, MD, 250-712-3900, DFinch-02@bccancer.bc.ca
BC Cancer - Surrey
Surrey, British Columbia, V3V 1Z2
Dr. Krista Noonan, MD, 604-930-2098, KNoonan2@bccancer.bc.ca
BC Cancer - Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
Dr. Guliz Ozgun, MD, 604-877-6000 ext. 676225, guliz.ozgun@bccancer.bc.ca
BC Cancer - Victoria
Victoria, British Columbia, V8R 6V5
Dr. Richard Gagnon, MD, 250-519-5500, Richard.Gagnon@islandhealth.ca
About this study
Official title: CHRONO-EVP: Time-of-day Dependent Administration of Enfortumab Vedotin and Pembrolizumab (EV/P) in Advanced Bladder 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 enfortumab vedotin and pembrolizumab (EV/P) works to treat adults with advanced bladder cancer. The trial will also learn if time-of-day reduces EV/P side-effects.
Researchers will compare EV/P given in the morning (before 11:30am) vs in the afternoon (after 1:30pm), to see if circadian rhythm effects how EV/P works to treat advanced bladder cancer.
Read more
Participants will be randomized in Arm A or Arm B to receive drugs EV/P either in the morning (Arm A) or afternoon (Arm B) as part of their standard-of-care treatment for advanced bladder cancer. Participants will:
- Visit the clinic either in the morning (Arm A) or afternoon (Arm B) to receive EV/P treatment as part of their regular medical care for advanced bladder cancer
- Frequency of visits will follow standard-of-care guidelines
- Participants will be followed-up by the study team for up to 24 months.
- Conditions
- Advanced Bladder Cancer
- Being tested
- enfortumab vedotin and pembrolizumab (EV/P)
- Keywords
- time-of-day administration, chronotherapy, advanced bladder cancer, circadian rhythm, enfortumab vedotin and pembrolizumab (EV/P), urothelial cancer, chronoimmunotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enfortumab vedotin and pembrolizumab (EV/P)Drug
Participants will receive EV/P as part of their standard-of-care therapy administered either in the morning (Arm A) or afternoon (Arm B), as determined by randomization.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Morning EV/P Treatment | Active comparator | Participants will receive standard-of-care therapy (Ev/P) administered in the morning (before 11:30am). Receives: Drug: enfortumab vedotin and pembrolizumab (EV/P) |
| Arm B: Afternoon EV/P Treatment | Active comparator | Participants will receive standard-of-care therapy (EV/P) administered in the afternoon (after 1:30pm). Receives: Drug: enfortumab vedotin and pembrolizumab (EV/P) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate in in time-of-day administration of EV/P 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 review or investigator assessment. 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 end of follow-up at 24-months.
Secondary outcomes (9)
Evaluate Progression-Free Survival in time-of-day administration of EV/P
Progression-free Survival (PFS) will be determined by time of randomization to radiographic progression or death from any cause, whichever occurs first.
Measured: From enrollment to end of follow-up at 24-months.
Assess Overall-Survival in time-of-day administration of EV/P
Overall-survival (OS) is defined as the time from randomization to death from any cause. The 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.
Evaluate the Time-to-Treatment Failure in time-of-day administration of EV/P
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 quantitative changes in ctDNA Kinetics of time-of-day administration of EV/P
Quantitative changes in circulating tumour DNA (ctDNA) levels will be collected and measured at baseline, post-cycle 1 (~3 weeks), and at post-cycle 4 (~12 weeks) at first radiographic assessment, with correlation to response and survival outcomes.
Measured: Baseline, 3 weeks, and 12-weeks.
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
Circulating Tumor DNA (ctDNA) Analyses
Circulating tumor DNA (ctDNA) analyses will be performed on plasma samples collected at baseline (prior to treatment initiation), 3 weeks into treatment, and 12 weeks into treatment. ctDNA dynamics will be evaluated to assess molecular response to therapy, including changes in ctDNA levels and ctDNA clearance rates over time. Comparisons will be made between treatment administration at different times of day to determine whether timing of therapy is associated with differences in ctDNA kinetics, clearance rates, and early molecular response.
Measured: At 3 time points: Baseline, 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 posted16 Jan 2026
- Study startNov 2026 (estimated)
- Primary completionDec 2030 (estimated)
- Study completionDec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Advanced Bladder 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 enfortumab vedotin and pembrolizumab (EV/P) 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. To preserve the immune priming effect, which is most pronounced during the initial treatment period, infusion timing will be strictly enforced during the first four cycles. After this period, patients will be allowed to have a flexible schedule. Treatment will be initiated in accordance with the standard of care, with no additional interventions planned. The trial is open-label and not blinded due to the nature of the intervention (timing of treatment).
- Masking
- None (open label)
- Enrolment
- 224 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
- NCT07346053
- Sponsor's protocol ID
- Chrono-EVP
- Acronym
- Chrono-EVP
- Status last verified
- Sep 2026
- First submitted
- 8 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 34615982Goncalves L, Guedes H, Fortuna AR, Lemos T, Gramaca J, Mourao N, Cunha G, Pichel R, Simoes P, Luis JA, Freitas R, Dunoes I, Spencer AS, Marinho J, Costa L. Avelumab Maintenance Therapy in Advanced Urothelial Carcinoma: Implications of Timing and Treatment Sequencing. Cancers (Basel). 2025 Mar 6;17(5):898. doi: 10.3390/cancers17050898.
PubMed 40075745Giacchetti 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 20055686Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, Iyer G, Vulsteke C, Park SH, Shin SJ, Castellano D, Fornarini G, Li JR, Gumus M, Mar N, Loriot Y, Flechon A, Duran I, Drakaki A, Narayanan S, Yu X, Gorla S, Homet Moreno B, van der Heijden MS; EV-302 Trial Investigators. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024 Mar 7;390(10):875-888. doi: 10.1056/NEJMoa2312117.
PubMed 38446675
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-EVP: Time-of-day Dependent Administration of Enfortumab Vedotin and Pembrolizumab (EV/P) in Advanced Bladder Cancer
- ClinicalTrials.gov ID
- NCT07346053
- Acronym / sponsor ID
- Chrono-EVP / Chrono-EVP
- Conditions
- Advanced Bladder Cancer
- Keywords
- time-of-day administration, chronotherapy, advanced bladder cancer, circadian rhythm, enfortumab vedotin and pembrolizumab (EV/P), urothelial cancer, chronoimmunotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 224 participants (estimated)
- Lead sponsor
- Guliz OzgunUniversity, hospital or other
- Collaborators
- British Columbia Cancer Agency
- Study start
- Nov 2026 (estimated)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2032 (estimated)
- First posted
- 16 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 enfortumab vedotin and pembrolizumab (EV/P) works to treat adults with advanced bladder cancer. The trial will also learn if time-of-day reduces EV/P side-effects.
Researchers will compare EV/P given in the morning (before 11:30am) vs in the afternoon (after 1:30pm), to see if circadian rhythm effects how EV/P works to treat advanced bladder cancer.
Participants will be randomized in Arm A or Arm B to receive drugs EV/P either in the morning (Arm A) or afternoon (Arm B) as part of their standard-of-care treatment for advanced bladder cancer. Participants will:
- Visit the clinic either in the morning (Arm A) or afternoon (Arm B) to receive EV/P treatment as part of their regular medical care for advanced bladder cancer
- Frequency of visits will follow standard-of-care guidelines
- Participants will be followed-up by the study team for up to 24 months.
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 enfortumab vedotin and pembrolizumab (EV/P) 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. To preserve the immune priming effect, which is most pronounced during the initial treatment period, infusion timing will be strictly enforced during the first four cycles. After this period, patients will be allowed to have a flexible schedule. Treatment will be initiated in accordance with the standard of care, with no additional interventions planned. The trial is open-label and not blinded due to the nature of the intervention (timing of treatment).
| Arm | Type | Receives |
|---|---|---|
| Arm A: Morning EV/P Treatment | Active comparator | Drug: enfortumab vedotin and pembrolizumab (EV/P)Participants will receive standard-of-care therapy (Ev/P) administered in the morning (before 11:30am). |
| Arm B: Afternoon EV/P Treatment | Active comparator | Drug: enfortumab vedotin and pembrolizumab (EV/P)Participants will receive standard-of-care therapy (EV/P) 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 inclusion criteria to be eligible for participation in this trial:
Key exclusion criteria (10 listed)
- Participants who meet any of following exclusion criteria will not be eligible for participation in this trial:
- Waivers to the exclusion criteria will NOT be allowed.
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 |
|---|---|---|
| enfortumab vedotin and pembrolizumab (EV/P)Participants will receive EV/P as part of their standard-of-care therapy administered either in the morning (Arm A) or afternoon (Arm B), as determined by randomization. | Drug | Arm A: Morning EV/P Treatment, Arm B: Afternoon EV/P Treatment |
Primary outcome
Objective response rate in in time-of-day administration of EV/P treatment
Time frame: From enrollment to end of follow-up at 24-months.
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 review or investigator assessment. 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.
9 secondary outcomes
Evaluate Progression-Free Survival in time-of-day administration of EV/P
Time frame: From enrollment to end of follow-up at 24-months.
Assess Overall-Survival in time-of-day administration of EV/P
Time frame: From enrollment to the end of follow-up at 24-months.
Evaluate the Time-to-Treatment Failure in time-of-day administration of EV/P
Time frame: From enrollment to the end of follow-up at 24-months.
Assess quantitative changes in ctDNA Kinetics of time-of-day administration of EV/P
Time frame: Baseline, 3 weeks, and 12-weeks.
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
Circulating Tumor DNA (ctDNA) Analyses
Time frame: At 3 time points: Baseline, 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 40075745Goncalves L, Guedes H, Fortuna AR, Lemos T, Gramaca J, Mourao N, Cunha G, Pichel R, Simoes P, Luis JA, Freitas R, Dunoes I, Spencer AS, Marinho J, Costa L. Avelumab Maintenance Therapy in Advanced Urothelial Carcinoma: Implications of Timing and Treatment Sequencing. Cancers (Basel). 2025 Mar 6;17(5):898. doi: 10.3390/cancers17050898.
- 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 38446675Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, Iyer G, Vulsteke C, Park SH, Shin SJ, Castellano D, Fornarini G, Li JR, Gumus M, Mar N, Loriot Y, Flechon A, Duran I, Drakaki A, Narayanan S, Yu X, Gorla S, Homet Moreno B, van der Heijden MS; EV-302 Trial Investigators. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024 Mar 7;390(10):875-888. doi: 10.1056/NEJMoa2312117.
- 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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing enfortumab vedotin and pembrolizumab (EV/P) in people with Advanced Bladder Cancer, run by Guliz Ozgun at 5 sites 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 10 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 5 sites 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. 676225, 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?
Objective response rate in in time-of-day administration of EV/P treatment (time frame: From enrollment to 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 NCT07346053, which also lists 7 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.