Urothelial Cancer
Conditions
Keywords
enfortumab vedotin, Pembrolizumab, peripheral neuropathy, metastatic urothelial carcinoma, advanced urothelial carcinoma
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.
Interventions
None listed
Sponsors
Comprehensive Cancer Center Munich (CCCM)
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 design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of peripheral neuropathy ≥ CTCAE grade 2 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change of degree of sensory, motor and/or autonomic peripheral neuropathy applying the EORTC-CIPN20 questionnaire | 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. |
| Change of Quality of life (QoL) applying the FACT/GOG-NTX questionnaire | 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. |
| Change of neuropathic pain applying the Neuropathic Pain Symptom Inventory (NPSI) questionnaire | 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. |
| Change of depression based on the Allgemeine Depressionsskala (ADS) | 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. |
| 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 | 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. |
| Change in nerve conduction studies, as measured by neurography, in the right sural (sensory) nerve | 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. |
| 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 | 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 |
| real world Progression free survival (rw-PFS) | 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. |
Countries
Germany
Outcome results
None listed