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NCT Number: NCT06657157

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

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.

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Key information

Conditions

Urothelial Cancer Carcinoma Carcinoma, Transitional Cell Neoplasms Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Nervous System Diseases Neuromuscular Diseases Peripheral Nervous System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Urology, University Hosptial Augsburg, Augsburg, Bavaria, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. 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)

  12. 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

  13. 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.

Sponsors and collaborators

Lead sponsor

Comprehensive Cancer Center Munich (CCCM)

Other

Collaborators

  • Department of Urology, Augsburg University Hospital, Augsburg, Germany
  • Department of Urology, TUM Klinikum rechts der Isar, Munich, Germany
  • Ludwig-Maximilians - University of Munich
  • Wuerzburg University Hospital

Registry information

Official study 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.

Acronym: P-EVOLUTION

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Oct 24, 2024
Registry last updated
Feb 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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