Clinical trial NCT06657157: Peripheral Neuropathy in Patients Receiving Enfortumab Vedotin and Pembrolizumab As First Line Treatment for Metastatic or Locally Advanced Urothelial Carcinoma
Official title: Peripheral Neuropathy in Patients Receiving Pembrolizumab and Enfortumab Vedotin As First Line Treatment for Metastatic or Locally Advanced Urothelial Carcinoma. an Investigator-Initiated, Prospective, Multicenter, Non-Interventional Trial.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Urothelial Cancer
Keywords: enfortumab vedotin
Pembrolizumab
peripheral neuropathy
metastatic urothelial carcinoma
advanced urothelial carcinoma
Lead sponsor: LMU Klinikum
Sponsor class: OTHER
Collaborators: name: Klinikum rechts der Isar, Technical University of Munich
First posted: 2024-10-24
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients meeting the eligibility criteria and are treated at the tertiary care centers LMU Munich and TUM Munich.

Brief summary: The P-EVOLUTION trial is a prospective, multicenter, non-interventional observational study aimed at investigating peripheral neuropathy in patients receiving first-line treatment for metastatic or locally advanced urothelial carcinoma with enfortumab vedotin (EV) and pembrolizumab (P). Conducted at two German university hospitals, the study will track the incidence and severity of peripheral neuropathy, its impact on quality of life, and treatment regimen adjustments due to side effects. Approximately 80 patients are expected to be enrolled over one year.


Eligibility criteria: Inclusion Criteria:

* Adult patients, ≥18 years of age at the time of signing the informed consent form (ICF)
* Patients with histologically confirmed metastatic or locally advanced, unresectable urothelial carcinoma
* Patients who did not receive any systemic treatment for their laUC or mUC (treatment-naïve)
* Patients who are able to receive enfortumab vedotin and pembrolizumab according to the respective medicinal product information

Exclusion Criteria:

* Patients with contraindications for enfortumab vedotin and/or pembrolizumab
* Patients who have received a systemic therapy for their laUC or mUC (e.g. platinum-based chemotherapy, checkpoint-inhibitors)
* Patients who have previously been treated with enfortumab vedotin, other MMAE-based antibody-drug-conjugates or PD-(L)1-checkpoint inhibitors
* Patients who received neoadjuvant or adjuvant platinum-based chemotherapy \<12 months ago

Primary outcomes:
measure: Incidence of peripheral neuropathy ≥ CTCAE grade 2
timeFrame: baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
Secondary outcomes:
measure: Change of degree of sensory, motor and/or autonomic peripheral neuropathy applying the EORTC-CIPN20 questionnaire
timeFrame: Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
measure: Change of Quality of life (QoL) applying the FACT/GOG-NTX questionnaire
timeFrame: Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
measure: Change of neuropathic pain applying the Neuropathic Pain Symptom Inventory (NPSI) questionnaire
timeFrame: Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
measure: Change of depression based on the Allgemeine Depressionsskala (ADS)
timeFrame: Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
measure: Time to onset of peripheral neuropathy ≥ CTCAE grade 2
timeFrame: From the administration of the first dose of EV/P to the end of treatment (defined as the administration of the final dose of EV/P), which is expected to occur after approximately one year.
measure: Number of dose reductions, delays or treatment discontinuation due to peripheral neuropathy or other adverse events
timeFrame: From the administration of the first dose of EV/P to the end of treatment (defined as the administration of the final dose of EV/P), which is expected to occur after approximately one year.
measure: Number of cycles of EV + P administered
timeFrame: From the administration of the first dose of EV/P to the end of treatment (defined as the administration of the final dose of EV/P), which is expected to occur after approximately one year.
measure: Change in nerve conduction studies, as measured by neurography, in the right tibial (motor) nerve
timeFrame: Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
measure: Change in nerve conduction studies, as measured by neurography, in the right sural (sensory) nerve
timeFrame: Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
measure: Changes in hand force as measured with a Martin-Vigorimeter
timeFrame: Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
measure: Changes in sensory perception using a monofilament test
timeFrame: Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
measure: Overall survival
timeFrame: From administration of first dose to date of death of any cause, assessed for up to 60 months
measure: real world Progression free survival (rw-PFS)
timeFrame: From administration of the first dose of EV/P to the first documented disease progression, as determined by the investigator, or to death from any cause, whichever occurs first, assessed up to 60 months.
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Urology, LMU University Hospital, Ludwig-Maximilians-University Munich
state: BY
city: Munich
country: Germany
facility: Department of Urology, Klinikum rechts der Isar, Technical University Munich
state: BY
Study officials:
References: