E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bladder Cancer |
Cáncer de vejiga |
|
E.1.1.1 | Medical condition in easily understood language |
Bladder Cancer |
Cáncer de vejiga |
|
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 compare the EFS per PRC of nivolumab plus BCG vs BCG alone in all randomized participants. |
_ Comparar la SLA según PRC de nivolumab más BCG frente a BCG en monoterapia en todos los pacientes aleatorizados. |
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E.2.2 | Secondary objectives of the trial |
_To compare the WFS of nivolumab plus BCG vs BCG alone in all randomized participants; _To compare the OS of nivolumab plus BCG vs BCG alone in all randomized participants; _To evaluate the CRR at first disease assessment (Week 13) in all randomized participants with CIS (+/- papillary disease) at study entry by treatment arm (nivolumab plus BCG and BCG alone); _evaluate the duration of response (DoR) in all randomized participants with CIS (+/- papillary disease) at study entry who achieved CRR at first disease assessment by treatment arm (nivolumab plus BCG and BCG alone); _To describe the safety and tolerability of nivolumab plus BCG and BCG alone in all treated participants. |
_ Comparar la SLE de nivolumab más BCG frente a BCG en monoterapia en todos los pacientes aleatorizados. _ Comparar la SG de nivolumab más BCG frente a BCG en monoterapia en todos los pacientes aleatorizados. _Evaluar la TRC en la primera evaluación de la enfermedad (semana 13) en todos los pacientes aleatorizados con CIS (+/- enfermedad papilar) a la entrada en el estudio por brazo de tratamiento (nivolumab más BCG y BCG en monoterapia). _ Evaluar la duración de la respuesta (DdR) en todos los pacientes aleatorizados con CIS (+/- enfermedad papilar) a la entrada en el estudio que hayan alcanzado la TRC en la primera evaluación de la enfermedad por grupo de tratamiento (nivolumab más BCG y BCG en monoterapia). _ Describir la seguridad y la tolerabilidad de nivolumab más BCG y BCG en monoterapia en todos los pacientes tratados. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
_Signed Written Informed Consent; _Histologically confirmed persistent or recurrent high-risk non-muscle-invasive UC (TaHG and/or T1 and/or CIS); _Treated with at least 1 adequate course of induction BCG therapy (at least 5 out of 6 doses); _Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2; _Males and females, ages 18 or age of majority, and older; |
_ Consentimiento informado por escrito firmado; _ CU no musculoinvasivo, confirmado histológicamente, persistente o recurrente, de alto riesgo (Ta de alto grado [TaAG] y/o T1 y/o CIS); _Tratamiento con al menos 1 ciclo adecuado de inducción con BCG (al menos 5 de 6 dosis); _Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0-2; _Varones y mujeres, de 18 años o más o con mayoría de edad; |
|
E.4 | Principal exclusion criteria |
_Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured or not requiring treatment; _Patients with serious or uncontrolled medical disorders; _Participants with an active, known, or suspected autoimmune disease; _Recurrent high-risk NMIBC that is classified as BCG unresponsive; _Has any contraindication to intravesical BCG therapy, including evidence of active tuberculosis; |
_Malignidad activa previa en los 3 años anteriores, excepto cánceres curables localmente que aparentemente han sido curados o que no requieren tratamiento; _Pacientes con trastornos médicos graves o no controlados; _Participantes con una enfermedad autoinmune activa, conocida o sospechada; _CVNMI recidivante de alto riesgo que se clasifique como sin respuesta a BCG; _Cualquier contraindicación a la terapia con BCG intravesical, incluyendo evidencia de tuberculosis activa; |
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E.5 End points |
E.5.1 | Primary end point(s) |
_EFS, defined as the time from randomization until any of the following events: recurrence (TaHG, T1 or CIS) or progression of disease, or death from any cause. |
_SLA, definida como tiempo desde la aleatorización hasta cualquiera de los siguientes acontecimientos: recidiva (TaAG, T1 o CIS) o progresión de la enfermedad o muerte por cualquier causa. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
_recurrence (TaHG, T1 or CIS) or progression of disease, or death from any cause. |
_recidiva (TaAG, T1 o CIS) o progresión de la enfermedad o muerte por cualquier causa. |
|
E.5.2 | Secondary end point(s) |
_WFS, defined as the time from randomization to progression to muscle invasive disease, cystectomy, systemic chemotherapy, radiotherapy, or death from any cause; _OS, defined as the time from randomization to death from any cause; _CRR, defined as the proportion of participants with CIS (+/- papillary disease) at study entry who are disease free at the first disease assessment; _DoR is restricted to participants with CIS (+/- papillary disease) at study entry who are disease free at the first disease assessment and is defined as the time between the date of the first CR to the date of first documented recurrence, progression, or death due to any cause; _Overall safety and tolerability will be measured by the incidence of AEs, SAEs, AEs leading to discontinuation, IMAEs, deaths, and laboratory abnormalities and changes from baseline. |
_SLE, definida como tiempo desde la aleatorización hasta progresión a enfermedad musculoinvasiva, cistectomía, quimioterapia sistémica, radioterapia o muerte por cualquier causa; _SG, definida como tiempo desde la aleatorización hasta la muerte por cualquier causa; _TRC, definida como la proporción de pacientes con CIS (+/- enfermedad papilar) a la entrada en el estudio que estén libres de enfermedad en la primera evaluación de la enfermedad; _La DdR se limita a los pacientes con CIS (+/- enfermedad papilar) a la entrada en el estudio que estén libres de enfermedad en la primera evaluación de la enfermedad y se define como el tiempo entre la fecha de la primera RC y la fecha de la primera recidiva, progresión documentada o muerte por cualquier causa; _Se medirán la seguridad y tolerabilidad globales por la incidencia de AA, AAG, AA que conducen a suspensión, AAMI, muertes y anomalías de laboratorio y cambios respecto al momento basal. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
_(WFS) progression to muscle invasive disease, cystectomy, systemic chemotherapy, radiotherapy, or death from any cause; _(OS) death from any cause; _(CRR) first disease assessment; _(DoR ) first documented recurrence, progression, or death due to any cause; __(Overall safety and tolerability) discontinuation, IMAEs, deaths, and laboratory abnormalities and changes from baseline. |
_(SLE) progresión a enfermedad musculoinvasiva, cistectomía, quimioterapia sistémica, radioterapia o muerte por cualquier causa; _(SG) muerte por cualquier causa; _(TRC) primera evaluación de la enfermedad; _(DdR) primera recidiva, progresión documentada o muerte por cualquier causa; _(Seguridad y tolerabilidad globales) suspensión, AAMI, muertes y anomalías de laboratorio y cambios respecto al momento basal. |
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
Denmark |
Finland |
France |
Germany |
Greece |
Ireland |
Italy |
Netherlands |
Romania |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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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
|
LVLS |
Última visita del último paciente |
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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 | 9 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |