E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced/metastatic urothelial tract carcinoma with genetic alterations in ERBB receptors |
Patients présentant un carcinome urothélial avancé ou métastatique avec altérations génétiques au niveau des récepteurs ERBB. |
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E.1.1.1 | Medical condition in easily understood language |
urothelial cancer |
Cancer urothélial |
|
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 |
Assess efficacy of afatinib in urothelial cancer patients based on PFS |
Efficacité de l'afatinib chez des patients avec carcinome urothélial évalué suivant la SSP à 6 mois. |
|
E.2.2 | Secondary objectives of the trial |
objective response, best recist assessment, safety, survival |
Taux de réponses objectives, survie sans progression (évaluation suivant RECIST), survie globale, tolérance |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-recurrent or metastatic urothelial cancer
-patients must have failed prior platinum based treatment (adjuvant or 1st line)
- patients must have not received more than one line of prior systemic chemotherapy for recurrent/metastatic disease, and this previous chemotherapy should be platinum based (immunotherapy is not considered as a systemic chemotherapy)
-tumour sample for HER2/3 mutation testing and/or assessment of markers to determine basal histology must be available
Further criteria apply |
Carcinome urothélial à un stade localement avancé ou métastatique.
En progression suite à une chimiothérapie à base de platine (adjuvant ou première ligne)
Patients ayant reçu au plus une ligne de chimiothérapie à base de platine comme traitement de la maladie progressive ou métastatique (l'immunothérapie n'est pas considérée comme une chimiothérapie systémique).
Suivant l' examen de l'échantillon tumoral, détermination de mutations HER2/3 et des biomarqueurs déterminant l'histologie basale de la tumeur.
Autres critères. |
|
E.4 | Principal exclusion criteria |
-Prior use of EGFR, ERBB2 or ERBB3 targeted treatment
-Chemotherapy within 4 weeks prior to the start of study treatment. Biological therapy or investigational agents within 4 weeks prior to the start of study treatment or prior to passing 5 half-lives, i.e. systemic clearance, whatever comes first
-Known brain metastases or signs hereof, uncontrolled spinal cord compression or leptomeningeal carcinomatosis
Further criteria apply |
Traitements antérieurs par thérapies ciblées EGFR, ERBB2 ou ERBB3.
Chimiothérapie dans les 4 semaines précédant le début du traitement à l'étude. Traitement biologique ou traitements expérimentaux dans les 4 semaines précédant le début du traitement ou avant d'atteindre les 5 demi-vies (clairance systémique).Métastases cérébrales connues ou se manifestant par des signes cliniques, compression médullaire non contrôlée ou carcinome leptoméningé.
Autres critères. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1: Progression Free Survival at 6 months in Cohort A (defined as the proportion of patients who does not show disease progression by the 24-week tumour assessment).
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1. Survie sans progression à 6 mois pour la Cohorte A ( proportion de patients ne montrant pas de progression suivant une évaluation tumorale à la semaine 24) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1: 24 weeks
|
1: 24 semaines. |
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E.5.2 | Secondary end point(s) |
1: Objective response rate (ORR), defined as number of complete response (CR) or partial response (PR) according to RECIST 1.1.
2: Progression free survival (PFS).
3: Overall Survival (OS)
4: Disease Control Rate (DCR)
5: Duration of objective response (DOR)
6: Tumour shrinkage
|
1: Taux de réponses objectives (RO) défini suivant le nombre de réponses complètes 5RC) et de réponses partielles (RP) suivant les critères de RECIST 1.1.
2: Survie sans progression (SSP)
3: Survie globale (SG) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: From Baseline to End of Trial
2: From first drug administration to disease progression
3: From first drug adminitration to date of death
4: From first drug administration to disease progression
5: From first drug administration to disease progression
6: From first drug administration to disease progression
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1: De la baseline à la fin du traitement
2: De la première administration du traitement à l'étude jusqu'à progression de la maladie.
3: De la première administration du traitement à l'étude jusqu'au décès
4: De la première administration du traitement à l'étude jusqu'à progression de la maladie.
5: De la première administration du traitement à l'étude jusqu'à progression de la maladie.
6: De la première administration du traitement à l'étude jusqu'à progression de la maladie. |
|
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 | 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 | Information not present in EudraCT |
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 | 1 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 28 |