E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Muscle-invasive bladder cancer (MIBC) |
Cáncer de vejiga con invasión muscular |
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E.1.1.1 | Medical condition in easily understood language |
Bladder cancer that spreads beyond the inner lining of the bladder and into the muscle layer |
Cáncer de vejiga que se propaga al musculo grueso |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 antitumor activity measured as pT0N0 rate, defined as no evidence of residual disease based on pathological review of the surgical specimen •To assess the percentage of pathological downstaging response |
•Evaluar la actividad antitumoral según la tasa de pT0N0, definida como la no evidencia de enfermedad residual basándose en la revisión anatomopatológica de la muestra quirúrgica. •Evaluar el porcentaje de respuesta de disminución del estadio anatomopatológico |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the percentage of tumour downstaging •To estimate the event-free survival (EFS) •To estimate the overall survival (OS). •To evaluate the Objective Response Rate (ORR) after neoadjuvant treatment •To assess the safety profile and tolerability of both schemes •To calculate the rate of delay of surgery. |
•Evaluar el porcentaje de disminución del estadio del tumor, •Estimar la tasa de supervivencia •Estimar la supervivencia global . •Evaluar la tasa de respuesta objetiva en los sujetos después del tratamiento neoadyuvante •Evaluar el perfil de seguridad y de tolerabilidad de las dos pautas . •Calcular la tasa de demora de la intervención quirúrgica. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Biomarkers Analysis |
Análisis de biomarcadores |
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E.3 | Principal inclusion criteria |
1)Written informed consent stating that he or she understands the purpose of the study and the procedures involved and agrees to participate in the study. 2)Histologically confirmed diagnosis of MIBC (Stage T2-4a N0/N1 M0) obtained via a diagnostic or maximal TURBT performed no later than 3 months prior to start the screening visit. 3)Pure or predominant (≥50%) UC histology as determined at the local site. 4)Age ≥ 18 years. 5)Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 6)Decline or ineligible (“unfit”) for cisplatin-based chemotherapy 7)Presence of a selected FGFR alteration on analysis of tumour biopsy 8)Adequate organ function 9)No other malignancy 10)Willingness to avoid pregnancy or fathering children |
1)Consentimiento informado por escrito donde se declare que el/la paciente comprende el propósito del estudio y los procedimientos del mismo y acepta participar en el estudio. 2)Diagnóstico de cáncer de vejiga con invasión muscular (MIBC, muscle-invasive bladder cancer) confirmado histológicamente (estadio T2-4a N0/N1 M0) obtenido mediante resección transuretral del tumor vesical (TURBT, transurethral resection of bladder tumor) diagnóstica o máxima, realizada no más de 3 meses antes de comenzar la visita de selección. 3)Histología pura o predominante (≥50%) de carcinoma urotelial (UC, urothelial carcinoma), según determinación en el centro local. 4)Edad ≥ 18 años. 5)Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0-1. 6)El paciente rechaza o no es elegible (“no apto”) para quimioterapia a base de cisplatino; 7)Presencia de una determinada alteración del FGFR en el análisis de la biopsia tumoral 8)Función orgánica adecuada 9)Ausencia de otras neoplasias malignas 10)Disposición para evitar el embarazo o engendrar hijos |
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E.4 | Principal exclusion criteria |
1)Clinical evidence of N2-N3 tumours or metastatic bladder cancer. 2)Has tumour with any neuroendocrine or small cell component. 3)Patients who are not considered fit for cystectomy or reject cystectomy. 5)Prior FGFR-targeted or antiPD1/PDL1 systemic therapy. 6)Prior systemic therapy, radiation therapy, or surgery for bladder cancer |
1)Evidencia clínica de tumor N2-N3 o cáncer de vejiga metastásico. 2)Tumor con cualquier componente neuroendocrino o microcelular. 3)Pacientes no considerados aptos para la cistectomía o que rechacen esta intervención. 5)Tratamiento sistémico previo dirigido al FGFR o antiPD1/PDL1. 6)No se permite la práctica previa de tratamiento sistémico, radioterapia o cirugía para el cáncer de vejiga |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint(s) •Pathological complete response (pCR). •Pathological downstaging <ypT2. |
Criterios de valoración principales •Respuesta completa anatomopatológica (pCR) •Disminución del estadio anatomopatológico <ypT2. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After a maximum of 30 weeks from the start of treatment (First Follow- up visit ) on specimens obtained during radical cystectomy. |
Después de un máximo de 30 semanas desde el inicio del tratamiento (Primera visita de seguimiento ) en muestras obtenidas durante la cistectomía radical. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints •Rate of pathological downstaging (pDS) •Event-free Survival rate. •OS. •ORR according to RECIST, after neoadjuvant treatment. •Adverse events. •Rate of delay of surgery (classed as a delay event if performed > 6 weeks after last dose of treatment). |
Criterios de valoración secundarios •Tasa de disminución del estadio anatomopatológico (pDS, pathological downstaging) •Tasa de supervivencia sin acontecimientos •Supervivencia global •Tasa de respuesta objetiva según los RECIST, después de tratamiento neoadyuvante •Acontecimientos adversos •Tasa de demora de la intervención quirúrgica (se considera demora si la intervención se realiza >6 semanas después de la última dosis del tratamiento). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During treatment and follow-up period. |
Durante el tratamiento y periodo de seguimiento. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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) | No |
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 | 14 |
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 |
France |
Spain |
Italy |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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 |
Ultima visita del ultimo sujeto reclutado |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |