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.
Age 18 or older
Able to provide informed consent
Histologically confirmed advanced urothelial cancer
Eligible for standard-of-care EV/P regimen
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
Parallel
enfortumab vedotin and pembrolizumab (EV/P)
DrugParticipants 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.
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.
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.
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.
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.
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.
Click on the lead sponsor to view all of their trials.
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:
