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

Comprehensive Cancer Center Munich (CCCM)80 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

Conditions

Urothelial Cancer

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (4)

Outcomes

Primary Outcomes

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)

Time frame: baseline, week 18, week 36, week 52, and End of Treatment (defined as the administration of the last dose of EV/P)

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Number of dose reductions, delays or treatment discontinuation due to peripheral neuropathy or other adverse events

Number of cycles of EV + P administered

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.

Time frame: 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.

Time frame: 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)

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)

Overall survival

defined as the time from administration of the first dose to date of death due to any cause

Time frame: 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.

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.