E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer |
Pacientes con cáncer urotelial localmente avanzado irresecable o metastásico. |
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E.1.1.1 | Medical condition in easily understood language |
Advanced urothelial bladder cancer for patients who cannot undergo surgery. Cancer arising in the urinary bladder or in other urinary tract sites such as the renal pelvis, ureters and urethra |
Cáncer avanzado de vejiga urotelial para pacientes que no pueden someterse a cirugía. Cáncer que surge en la vejiga urinaria u otras partes del tracto urinario como pelvis renal, uréteres y uretra. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of durvalumab + SoC combination therapy versus SoC in terms of PFS/OS in patients with unresectable locally advanced or metastatic UC. |
Evaluar la eficacia del grupo de tratamiento 1 en comparación con el grupo de tratamiento 3 en cuanto a SSP/SG en pacientes con CU irresecable localmente avanzado o metastásico. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy in patients in different treatment arms
-To assess disease-related symptoms, physical functioning, and other health related quality of life in patients in different treatment arms |
-Evaluar la eficacia en pacientes en diferentes grupos de tratamiento. -Evaluar los síntomas relacionados con la enfermedad, la función física y otra CVRS en pacientes en diferentes grupos de tratamiento. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
-Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
-At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
-Adequate organ and marrow function as defined in the protocol
- Life expectancy ≥12 weeks in the opinion of the investigator
-Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. |
- Pacientes con carcinoma de células transicionales clínicamente o citológicamente documentado, irresecable, localmente avanzado o metastásico (células de transición y histologías mixtas de células transicionales / no transitorias) del urotelio (incluida la pelvis renal, los uréteres, la vejiga urinaria y la uretra)
- Pacientes que no han sido tratados previamente con quimioterapia en primera línea. Los pacientes que han recibido quimiorradiación definitiva, tratamiento adyuvante o neoadyuvante para la enfermedad localmente avanzada son elegibles siempre que la progresión a enfermedad localmente avanzada o metastásica haya ocurrido> 12 meses desde el último tratamiento [para quimiorradiación y tratamiento adyuvante] o> 12 meses desde el último cirugía [para tratamiento neoadyuvante].
-Al menos 1 lesión, no irradiada previamente, que califica como una lesión objetivo RECIST 1.1 al inicio del estudio.
- Estado funcional de la Organización Mundial de la Salud (OMS) / (ECOG) de 0 o 1 en el momento de la inclusión.
- Función adecuada de órgano y médula ósea como se define en el protocolo
- Esperanza de vida ≥12 semanas según la opinión del investigador
-Evidencia del estado posmenopáusico, o prueba de embarazo urinaria o sérica negativa para mujeres premenopáusicas. |
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E.4 | Principal exclusion criteria |
- Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
- No severe concomitant condition that requires immunosuppression medication
- Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
- Patients who may be eligible for or are being considered for radical resection during the course of the study.
- Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients |
Exposición previa a terapia inmunomediada (con exclusión de Bacillus Calmette Guerin), que incluye pero no se limita a, otros anticuerpos anti CTLA-4, anti PD 1, anti PD L1 o anti PD L2, excepto vacunas terapéuticas contra el cáncer, que están permitidas. Se permite quimioterapia o inmunoterapia intervesical local previa si se completa al menos 28 días antes del inicio del tratamiento del estudio.
- Ninguna condición concomitante grave que requiera medicamentos inmunosupresores
- Metástasis del sistema nervioso central (SNC) sin tratamiento y / o meningitis carcinomatosa
- Pacientes que pueden ser elegibles o que están siendo considerados para una resección radical durante el transcurso del estudio.
- Cualquier contraindicación médica para la quimioterapia con doblete basada en platino (cisplatino o carboplatino) y / o alergia o hipersensibilidad conocida a cualquiera de los medicamentos del estudio o cualquiera de los excipientes de los medicamentos del estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR - Overall Survival (OS) |
-Supervivencia sin progresión (SSP) por RECIST 1.1 según lo evaluado por BICR - Supervivencia global (SG) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessments for overall survival and progression free survival will be made periodically until the end of study. |
Las evaluaciones de supervivencia global y Supervivencia sin progresión se realizarán periódicamente hasta el final del estudio. |
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E.5.2 | Secondary end point(s) |
- Progression Free Survival (PFS) - Overall Survival (OS) - Alive and Progression Free Patients at 12 Months (APF12) - Overall Response Rate (ORR) - Disease Control Rate (DCR) - Duration of Response (DoR) - Time from Randomization to Second Progression PFS (PFS2) |
-Supervivencia sin progresión (SSP) - Supervivencia global (SG) - Pacientes vivos y libres de progresión a los 12 meses (APF12) - Tasa de respuesta objetiva (TRO) - Tasa de control de enfermedades (TCE) - Duración de la respuesta (DR) - Tiempo desde la aleatorización hasta la segunda progresión (VSP12) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessments will be made periodically until the end of study. |
Las evaluaciones se realizarán periódicamente hasta el final del estudio. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Bulgaria |
Canada |
China |
Czech Republic |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Philippines |
Poland |
Russian Federation |
Spain |
Taiwan |
Thailand |
Turkey |
United States |
Vietnam |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS
In the event that a roll-over or safety extension study is available at the time of the final data cut-off and database closure, patients currently receiving treatment with durvalumab may be transitioned to such a study, and the current study would reach its end. The roll-over or safety extension study would ensure treatment continuation with visit assessments per its protocol. Any patient who would be proposed to move to such a study would be given a new informed consent form (ICF). |
Si se dispone de estudio de renovación de seguridad o transferencia en el momento del corte final de datos o cierre de base de datos,pacientes que estén recibiendo tratamiento con durvalumab pueden trasladarse a este estudio,y el actual llegar a su fin.El reinicio o estudio de extensión de seguridad garantizaría continuación del tratamiento con evaluaciones de visitas según protocolo.Al paciente que se le proponga cambiar a dicho estudio se le dará un nuevo formulario de consentimiento(ICF). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |