The Impact of Time-of-day Administration of EV/P on Objective Response Rate in Adults With Advanced Bladder Cancer (Chrono-EVP)

Guliz Ozgun

Status and phase: Begins enrollment in 2 months; Phase 3

Conditions: Advanced Bladder Cancer

Treatments: Drug: enfortumab vedotin and pembrolizumab (EV/P)

Study type: Interventional

Funder types: Other

Identifiers

NCT07346053

Chrono-EVP

Details and patient eligibility

About

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.

Enrollment: 224 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must meet all of the following inclusion criteria to be eligible for participation in this trial:

  1. Age 18 or older
  2. Able to provide informed consent
  3. Histologically confirmed advanced urothelial cancer
  4. Eligible for standard-of-care EV/P 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) Waivers to the inclusion criteria will NOT be allowed.

Exclusion criteria

• Participants who meet any of following exclusion criteria will not be eligible for participation in this trial:

  1. Non-urothelial histology or mixed histology with predominant non-urothelial components
  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 at least the first 3 months
  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.

Waivers to the exclusion criteria will NOT be allowed.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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224 participants in 2 patient groups

Arm A: Morning EV/P Treatment

Active Comparator group

Description:

Participants will receive standard-of-care therapy (Ev/P) administered in the morning (before 11:30am).

Treatment:

Drug: enfortumab vedotin and pembrolizumab (EV/P)

Arm B: Afternoon EV/P Treatment

Active Comparator group

Description:

Participants will receive standard-of-care therapy (EV/P) administered in the afternoon (after 1:30pm).

Treatment:

Drug: enfortumab vedotin and pembrolizumab (EV/P)