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

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: Recruiting
• Conditions: Urothelial Cancer

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Augsburg, Bavaria, Germany, 86156
      • Recruiting
      • Department of Urology, University Hosptial Augsburg
      • Contact: Julie Steinestel, MD; Phone Number: +49 821 40001; Email: Julie.Steinestel@uk-augsburg.de
    • Munich, Bavaria, Germany, 81377
      • Recruiting
      • Department of Urology, LMU University Hospital, Ludwig-Maximilians-University Munich
      • Contact: Jozefina Casuscelli; Phone Number: +49 89 4400 0; Email: jozefina.casuscelli@med.uni-muenchen.de
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • Department of Urology, Klinikum rechts der Isar, Technical University Munich
      • Contact: Kira Schüller; Phone Number: +49 89 4140 0; Email: kira.shueller@tum.de
    • Würzburg, Bavaria, Germany, 97080
      • Recruiting
      • Department of Urology, University Hospital of Würzburg
      • Contact: Anna Seitz, MD; Phone Number: +49 931 2010; Email: Seitz_A3@ukw.de

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of peripheral neuropathy ≥ CTCAE grade 2	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

Outcome Measure	Measure Description	Time Frame
Change of degree of sensory, motor and/or autonomic peripheral neuropathy applying the EORTC-CIPN20 questionnaire	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	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	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)	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		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		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		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	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	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		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		Baseline, Week 18, End of Treatment (defined as the administration of the final dose of EV/P)
Overall survival	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)	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

• Sponsor: Comprehensive Cancer Center Munich (CCCM)
• Collaborators: 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

Study Major Dates

• Study Start (Actual): January 22, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: October 19, 2024
• First Submitted That Met QC Criteria: October 22, 2024
• First Posted (Actual): October 24, 2024

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 21, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: peripheral neuropathy; Pembrolizumab; enfortumab vedotin; metastatic urothelial carcinoma; advanced urothelial carcinoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Peripheral Nervous System Diseases; Carcinoma, Transitional Cell
• Other Study ID 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