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    Summary
    EudraCT Number:2018-001883-48
    Sponsor's Protocol Code Number:D933SC00001
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-08-12
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-001883-48
    A.3Full title of the trial
    Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination with Standard of Care Chemotherapy and Durvalumab in Combination with Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer
    Studio internazionale multicentrico controllato randomizzato di fase III, in aperto, sul trattamento di prima linea con Durvalumab in combinazione con la chemioterapia standard e con Durvalumab in combinazione con Tremelimumab e la chemioterapia standard verso la chemioterapia standard in monoterapia in pazienti affetti da tumore uroteliale non operabile, localmente avanzato o metastatico
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of Durvalumab Given with Chemotherapy, Durvalumab in Combination with Tremelimumab Given with Chemotherapy, or Chemotherapy in Patients with Advanced Urothelial
    Bladder Cancer
    Studio con Durvalumab somministrato con la chemioterapia, Durvalumab in combinazione con Tremelimumab somministrato con la chemioterapia, o chemioterapia in pazienti con tumore uroteliale della vescica avanzato
    A.3.2Name or abbreviated title of the trial where available
    Nile
    Nile
    A.4.1Sponsor's protocol code numberD933SC00001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03682068
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorASTRAZENECA AB
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca Clinical
    B.5.2Functional name of contact pointClinical Trial Transparency
    B.5.3 Address:
    B.5.3.1Street Address15185
    B.5.3.2Town/ citySodertalje
    B.5.3.3Post codeSE 151 85
    B.5.3.4CountrySweden
    B.5.6E-mailclinicaltrialtransparency@astrazeneca.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namedurvalumab
    D.3.2Product code [MEDI4736]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNdurvalumab
    D.3.9.1CAS number 1428935-60-7
    D.3.9.2Current sponsor codeMEDI4736
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nametremelimumab
    D.3.2Product code [MEDI1123]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 745013-59-6
    D.3.9.2Current sponsor codeMEDI1123
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer
    Pazienti con tumore uroteliale localmente avanzato o metastatico, non operabile
    E.1.1.1Medical 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
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10005003
    E.1.2Term Bladder cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main 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.
    E.2.2Secondary 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.
    E.2.3Trial contains a sub-study No
    E.3Principal 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.
    E.4Principal 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.
    E.5 End points
    E.5.1Primary end point(s)
    Overall Survival (OS)
    Sopravvivenza globale (OS)
    E.5.1.1Timepoint(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.
    E.5.2Secondary 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
    E.5.2.1Timepoint(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.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA49
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If 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
    E.8.7Trial 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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 574
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 860
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    A legal representative may provide consent on behalf of a subject incapable of giving consent personally, where permitted by local regulations
    Un rappresentante legale potrà fornire il consenso informato al posto del soggetto incapace di fornire il suo consenso personalmente, qualora permesso dalla normativa locale
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 351
    F.4.2.2In the whole clinical trial 1434
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients who continue to receive benefit from their assigned treatment at the end of study may continue to receive their assigned treatment for as long as they and their physician feel they are gaining clinical benefit.
    Pazienti che continuano a trarre giovamento dal trattamento a loro assegnato alla fine dello studio possono continuare a ricevere il trattamento assegnato finché il giovamento continui ad essere riscontrato da loro stessi e dal loro medico .
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-12-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-10-26
    P. End of Trial
    P.End of Trial StatusOngoing
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