Perioperative Systemic Therapies in Muscle-Invasive Bladder Cancer (GUARDIANS) (GUARDIANS)
Perioperative GUARDIANS Project: Real-World Evaluation of Feasibility, Toxicity, and Oncologic Outcomes of Perioperative Systemic Therapies in Muscle-Invasive Urothelial Carcinoma
This is a multicenter, non-interventional, prospective and retrospective observational patient registry study of adults with muscle-invasive bladder cancer receiving perioperative systemic therapy as part of routine clinical care. The registry includes patients treated with perioperative systemic therapies such as Enfortumab Vedotin plus Pembrolizumab as well as cisplatin-based combinations including Gemcitabine/Cisplatin/Durvalumab and other standard perioperative treatment approaches in the neoadjuvant and adjuvant setting.
The study aims to evaluate real-world feasibility, treatment tolerability, pathologic response, and oncologic outcomes of perioperative systemic treatment strategies. Key outcomes include event-free survival (EFS), pathologic complete response (pCR), pathologic downstaging, disease-free survival (DFS), overall survival (OS), perioperative complications, and treatment-related adverse events. Patient-reported neurotoxicity symptoms will also be assessed using standardized neuropathy questionnaires.
All treatments, surgeries, and follow-up procedures are performed according to routine clinical practice. No study-specific interventions are assigned. Clinical data are collected pseudonymized through participating GUARDIANS centers using standardized electronic case report forms. Both prospective and retrospective data collection are included.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
The GUARDIANS perioperative registry is a multicenter observational study designed to collect real-world data on perioperative systemic therapies in patients with muscle-invasive or locally advanced urothelial carcinoma of the bladder.
Perioperative systemic treatment strategies for muscle-invasive bladder cancer are rapidly evolving and include antibody-drug conjugate-based combinations such as Enfortumab Vedotin plus Pembrolizumab as well as cisplatin-based regimens including Gemcitabine/Cisplatin/Durvalumab and other standard neoadjuvant and adjuvant treatment approaches. While these regimens are increasingly used in routine care, systematic real-world evidence regarding feasibility, dose intensity, perioperative safety, patient-reported neurotoxicity, pathologic response, and long-term oncologic outcomes remains limited.
This registry evaluates perioperative treatment strategies with particular focus on real-world implementation, treatment completion, and comparative outcomes across different systemic therapy approaches. Patients are followed longitudinally from baseline and diagnosis through neoadjuvant therapy, radical cystectomy with pelvic lymph node dissection, adjuvant therapy when applicable, and long-term follow-up.
The primary objective is evaluation of event-free survival (EFS) and treatment feasibility. Feasibility includes completion of intended radical cystectomy, delivery of planned neoadjuvant and adjuvant treatment components, and reasons for treatment delay, modification, or discontinuation.
Secondary objectives include assessment of:
Pathologic complete response (pCR, ypT0N0) Pathologic downstaging Disease-free survival (DFS) Overall survival (OS) Local and distant recurrence patterns 90-day postoperative complications after radical cystectomy CTCAE version 5.0 treatment-related toxicities Patient-reported chemotherapy-induced peripheral neuropathy symptoms Treatment exposure and dose intensity The study is non-interventional. All diagnostic and therapeutic decisions are made independently of study participation according to local standard of care. No additional mandatory visits, diagnostic procedures, or therapeutic interventions are required.
Data are collected pseudonymized using REDCap across participating GUARDIANS centers. Prospective collection includes patient-reported outcome measures for neurotoxicity, while retrospective collection allows inclusion of previously treated patients according to ethics approval and local regulations. The registry supports evaluation of real-world outcomes across multiple perioperative treatment strategies and provides comparative evidence for routine clinical practice.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Munich, Alemania, 81377
- Reclutamiento
- Department of Urology, LMU University Hospital Munich
-
Contacto:
- Can Aydogdu, MD
- Número de teléfono: +49 89 4400 0
- Correo electrónico: can.aydogdu@med.uni-muenchen.de
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Adult patients with muscle-invasive or locally advanced urothelial carcinoma of the bladder receiving perioperative systemic therapy in routine clinical practice. Patients are treated in the neoadjuvant and/or adjuvant setting with curative intent and undergo or are planned for radical cystectomy with pelvic lymph node dissection. Treatment approaches include Enfortumab Vedotin plus Pembrolizumab, Gemcitabine/Cisplatin/Durvalumab, cisplatin-based chemotherapy, immunotherapy, and other standard perioperative systemic therapies. Both prospective and retrospective patients from participating GUARDIANS centers are included.
Descripción
Inclusion Criteria:
- Age ≥18 years
- Histologically confirmed muscle-invasive or locally advanced urothelial carcinoma of the bladder
- Planned, ongoing, or completed perioperative systemic therapy, including but not limited to Enfortumab Vedotin plus Pembrolizumab, Gemcitabine/Cisplatin/Durvalumab, cisplatin-based chemotherapy, immunotherapy, or other standard perioperative treatment approaches
- Radical cystectomy planned or performed as part of curative-intent treatment strategy
- Written informed consent for prospective data collection, where required
- Sufficient clinical documentation available for retrospective inclusion, including at least one follow-up assessment
Exclusion Criteria:
- Missing informed consent where prospectively required
- Insufficient documentation of key baseline data or treatment exposure
- No perioperative systemic therapy or inability to assign patient to a study cohort
- Follow-up data unavailable or inconsistent documentation preventing endpoint assessment
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: COHORT
- Perspectivas temporales: PROSPECTIVE
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
Event Free Survival (EFS)
Periodo de tiempo: From treatment initiation up to 36 months
|
From treatment initiation up to 36 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Pathologic Complete Response (pCR)
Periodo de tiempo: At radical cystectomy
|
At radical cystectomy
|
|
|
Pathologic Downstaging
Periodo de tiempo: At radical cystectomy
|
Defined as less than ypT2N0 in the cystectomy specimen, including pT0, pTis, pTa, and pT1. |
At radical cystectomy
|
|
Disease-Free Survival (DFS)
Periodo de tiempo: Up to 36 months after surgery
|
Time from curative surgery until recurrence or death. |
Up to 36 months after surgery
|
|
Overall Survival (OS)
Periodo de tiempo: Up to 60 months
|
Time from treatment initiation until death from any cause. |
Up to 60 months
|
|
Change Over Time in Patient-Reported Peripheral Neuropathy Assessed by the EORTC QLQ-CIPN20
Periodo de tiempo: Baseline; within 14 days before radical cystectomy; start of adjuvant therapy ±14 days; weeks 12, 21, and 30 of adjuvant therapy ±14 days; and end of treatment ±14 days
|
Patient-reported peripheral neuropathy symptoms will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20). The questionnaire assesses sensory, motor, and autonomic symptoms of peripheral neuropathy. Subscale scores are calculated according to the EORTC scoring procedure and linearly transformed to a scale ranging from 0 to 100. Higher scores indicate greater peripheral neuropathy symptom burden and therefore a worse outcome. Changes from baseline will be assessed longitudinally during perioperative treatment through end of treatment. |
Baseline; within 14 days before radical cystectomy; start of adjuvant therapy ±14 days; weeks 12, 21, and 30 of adjuvant therapy ±14 days; and end of treatment ±14 days
|
|
Treatment-Related Adverse Events
Periodo de tiempo: From first administration of neoadjuvant therapy through the end-of-treatment visit, up to approximately 12 months
|
Occurrence, type, severity, attribution, management, and outcome of treatment-related adverse events associated with perioperative enfortumab vedotin and pembrolizumab. Adverse event severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. |
From first administration of neoadjuvant therapy through the end-of-treatment visit, up to approximately 12 months
|
|
90-Day Postoperative Complications
Periodo de tiempo: Up to 90 days after radical cystectomy
|
Occurrence and severity of postoperative complications within 90 days after radical cystectomy, graded according to the Clavien-Dindo classification. |
Up to 90 days after radical cystectomy
|
|
90-Day Perioperative Mortality
Periodo de tiempo: Up to 90 days after radical cystectomy
|
All-cause mortality occurring within 90 days after radical cystectomy following perioperative systemic therapy. This includes deaths related to surgical complications, treatment-related toxicity, or other causes during the perioperative period. |
Up to 90 days after radical cystectomy
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
- Gemcitabina
- Carcinoma urotelial
- Cisplatino
- Cistectomía radical
- Pembrolizumab
- Terapia Neoadyuvante
- Durvalumab
- Respuesta patológica completa
- CIPN
- Terapia adyuvante
- Registro de pacientes
- Datos del mundo real
- Enfortumab vedotina
- Cáncer de vejiga con invasión muscular
- Supervivencia Libre de Eventos
- Perioperative Systemic Therapy
- GUARDIANS
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- GUARDIANS
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .