Peripheral Neuropathy in Patients Receiving Enfortumab Vedotin and Pembrolizumab as First Line Treatment for Metastatic or Locally Advanced Urothelial Carcinoma (P-EVOLUTION)

February 21, 2026 updated by: Can Aydogdu, MD, Comprehensive Cancer Center Munich (CCCM)

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.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Bavaria
      • Augsburg, Bavaria, Germany, 86156
        • Recruiting
        • Department of Urology, University Hosptial Augsburg
        • Contact:
      • Munich, Bavaria, Germany, 81377
        • Recruiting
        • Department of Urology, LMU University Hospital, Ludwig-Maximilians-University Munich
        • Contact:
      • Munich, Bavaria, Germany, 81675
        • Recruiting
        • Department of Urology, Klinikum rechts der Isar, Technical University Munich
        • Contact:
      • Würzburg, Bavaria, Germany, 97080
        • Recruiting
        • Department of Urology, University Hospital of Würzburg
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of peripheral neuropathy ≥ CTCAE grade 2
Time Frame: baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
Incidence of peripheral neuropathy ≥ grade 2 at baseline, week 18, week 36, week 52, and at End of Treatment (defined as the administration of the last dose of EV/P) assessed by the Patient Neurotoxicity Questionnaire (PNQ)
baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of degree of sensory, motor and/or autonomic peripheral neuropathy applying the EORTC-CIPN20 questionnaire
Time Frame: Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
A higher EORTC-CIPN20 score indicates a worse degree of neuropathy.
Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
Change of Quality of life (QoL) applying the FACT/GOG-NTX questionnaire
Time Frame: Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
An higher FACT/GOG-NTX score indicates a better QoL.
Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
Change of neuropathic pain applying the Neuropathic Pain Symptom Inventory (NPSI) questionnaire
Time Frame: Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
A higher NPSI score indicates more neuropathic pain.
Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
Change of depression based on the Allgemeine Depressionsskala (ADS)
Time Frame: Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
A higher ADS value indicates higher degree of depression.
Baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)
Time to onset of peripheral neuropathy ≥ CTCAE grade 2
Time Frame: 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.
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.
Number of dose reductions, delays or treatment discontinuation due to peripheral neuropathy or other adverse events
Time Frame: 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.
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.
Number of cycles of EV + P administered
Time Frame: 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.
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.
Change in nerve conduction studies, as measured by neurography, in the right tibial (motor) nerve
Time Frame: Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
A higher nerve conduction velocity indicates a faster transmission of electrical signal along the nerve. And vice versa.
Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
Change in nerve conduction studies, as measured by neurography, in the right sural (sensory) nerve
Time Frame: Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
A higher nerve conduction velocity indicates a faster transmission of electrical signal along the nerve. And vice versa.
Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
Changes in hand force as measured with a Martin-Vigorimeter
Time Frame: Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
Changes in sensory perception using a monofilament test
Time Frame: Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
Overall survival
Time Frame: From administration of first dose to date of death of any cause, assessed for up to 60 months
defined as the time from administration of the first dose to date of death due to any cause
From administration of first dose to date of death of any cause, assessed for up to 60 months
real world Progression free survival (rw-PFS)
Time Frame: 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.
rw-PFS, defined as the time from the 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Comprehensive Cancer Center Munich (CCCM)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Department of Urology, LMU University Hospital Munich, Munich, Germany
Department of Urology, TUM Klinikum rechts der Isar, Munich, Germany
Department of Urology, Augsburg University Hospital, Augsburg, Germany
Department of Urology, University Hospital of Würzburg, Würzburg, Germany

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 22, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 19, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 24, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P-EVOLUTION

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings