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 |
Pazienti con tumore uroteliale localmente avanzato o metastatico, non operabile |
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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 |
Tumore uroteliale avanzato della vescica in pazienti che non possono essere operati. Tumore che si sviluppa nella vescica o in altri punti del tratto urinario come pelvi renale, ureteri e 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 OS in patients with unresectable locally advanced or metastatic UC and high PD-L1 expression.
To assess the efficacy of durvalumab and tremelimumab + SoC combination therapy versus SoC in terms of OS in patients with unresectable locally advanced or metastatic UC and high PD-L1 expression. |
Valutare l'efficacia della terapia di combinazione durvalumab + SoC verso la sola SoC in termini di OS in pazienti con tumore uroteliale localmente avanzato o metastatico non operabile e livello alto di espressione di PD-L1.
Valutare l'efficacia della terapia di combinazione durvalumab + tremelimumab + SoC verso la sola SoC in termini di OS in pazienti con tumore uroteliale localmente avanzato o metastatico non operabile e livello alto di espressione di PD-L1. |
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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, safety, physical functioning, and other health related quality of life in patients in different treatment arms |
- Valutare l'efficacia in pazienti nei diversi bracci di trattamento
- Valutare i sintomi associati alla malattia, la sicurezza, il funzionamento fisico e altro associato alla qualità di vita in merito alla salute in pazienti nei diversi bracci di trattamento. |
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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. |
• Pazienti con carcinoma a cellule transizionali documentato istologicamente o citologicamente (con istologia a cellule transizionali e mista con cellule transizionali/non transizionali), non operabile, localmente avanzato o metastatico, dell’urotelio (inclusi pelvi renali, ureteri, vescica urinaria e uretra)
• Pazienti che non sono stati precedentemente trattati con una chemioterapia di prima linea. I pazienti che hanno precedentemente ricevuto una chemioradioterapia definitiva, un trattamento adiuvante o neoadiuvante per la patologia localmente avanzata sono eleggibili purchè la progressione a patologia localmente avanzata o metastatica sia avvenuta dopo più di 12 mesi dall’ultima terapia [per la chemioradioterapia e il trattamento adiuvante] o dopo più di 12 mesi dall’ultimo trattamento chirurgico [per il trattamento neoadiuvante]
• Almeno una lesione, non precedentemente irradiata, che sia qualificata come lesione target RECIST 1.1 al basale.
• Performance Status (PS) WHO (Word Health Organization)/ECOG (Eastern Cooperative Oncology Group) da 0 a 1 all’arruolamento.
• Adeguata funzionalità del midollo e degli organi come definito nel protocollo
• Aspettativa di vita maggiore o uguale a 12 settimane, secondo l’opinione dello sperimentatore
• Evidenza di stato di post-menopausa o test di gravidanza, urinario o plasmatico, negativo per le pazienti femmine in pre-menopausa. |
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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 |
• Precedente esposizione a terapia immuno-mediata (con esclusione di Bacillus Calmette Guerin) inclusi, ma non limitati a, altri anticorpi anti-CTLA-4, anti-PD-1, anti-PD-L1 o anti-PD-L2, eccetto vaccini terapeutici antitumorali, che sono consentiti. Un’antecedente chemioterapia locale endovescicale o immunoterapia è consentita se completata almeno 28 giorni prima dell’inizio del trattamento di studio
• Nessuna condizione concomitante severa che richieda un trattamento di immunosoppressione
• Metastasi non trattate del sistema nervoso centrale (CNS) e/o meningiti carcinomatose
• Pazienti che potrebbero essere eleggibili o sono stati considerati per una resezione radicale nel corso dello studio
• Qualsiasi controindicazione medica a una doppia chemioterapia basata sul platino (cisplatino o carboplatino) e/o nota allergia o ipersensibilità a uno qualsiasi dei farmaci dello studio o degli eccipienti dei farmaci dello studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Survival (OS) |
Sopravvivenza globale (OS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessments for overall survival will be made periodically until the end of study. |
Le valutazioni di OS saranno fatte periodicamente fino alla fine dello studio. |
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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) - Safety - Disease related symptoms |
- PFS (Progression Free Survival) - OS (Overall Survival) - APF12 (Alive and Progression Free Patients a 12 mesi) - ORR (Overall Response Rate) - DCR (Disease Control Rate) - Durata della Risposta (DoR) - Tempo dalla Randomizzazione alla Seconda Progressione PFS (PFS2) - Sicurezza - Sintomi associati alla malattia |
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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. |
Le valutazioni saranno fatte periodicamente fino alla fine dello studio. |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 | Information not present in EudraCT |
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 |
India |
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
|
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). |
LVLS-Se disponibile uno studio di estens. o di sicur. al momento del cutoff finale e della chiusura del database,i pz che al momento ricevono un trattamento con Durvalumab possono essere inseriti in tale studio, e lo studio corrente terminerebbe.Il roll-over o lo studio di sicur. di estens. assicurerebbe la continuazione del trattamento con le visite di valutaz.sul relativo protocollo.Un nuovo modulo di consenso inform.(ICF)verrebbe dato a qualsiasi pz che si proponesse di passare a tale studio |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 |