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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2018-004688-30
    Sponsor's Protocol Code Number:D933AC00001
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2019-04-24
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2018-004688-30
    A.3Full title of the trial
    A Phase III Randomized, Double-Blind Placebo Controlled, Multi-Regional, International Study of Durvalumab in Combination with Gemcitabine Plus Cisplatin Versus Placebo in Combination with Gemcitabine Plus Cisplatin for Patients With First-Line Advanced Biliary Tract Cancers
    Międzynarodowe badanie fazy III prowadzone w różnych regionach z zastosowaniem metody randomizacji i podwójnie ślepej próby, kontrolowane placebo, oceniające durwalumab w skojarzeniu z gemcytabiną i cisplatyną w porównaniu z placebo w skojarzeniu z gemcytabiną i cisplatyną w terapii pierwszego rzutu u pacjentów z zaawansowanymi nowotworami złośliwymi dróg żółciowych (TOPAZ-1)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Global Phase III Study of durvalumab or placebo in combination with gemcitabine/cisplatin in patients with 1st line advanced biliary tract cancers
    Globalne badanie fazy III oceniające stosowanie durwalumabu lub placebo w skojarzeniu z gemcytabiną/cisplatyną w terapii pierwszego rzutu u pacjentów z zaawansowanym rakiem dróg żółciowych
    A.3.2Name or abbreviated title of the trial where available
    TOPAZ-1 Study
    TOPAZ-1
    A.4.1Sponsor's protocol code numberD933AC00001
    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
    B.5.2Functional name of contact pointClinical Study Information Center
    B.5.3 Address:
    B.5.3.1Street AddressNA
    B.5.3.2Town/ cityNA
    B.5.3.3Post codeNA
    B.5.3.4CountryUnited States
    B.5.6E-mailinformation.center@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 and solvent for solution for infusion
    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.3.9.3Other descriptive namedurvalumab
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    First-line patients with advanced biliary tract cancers (BTC)
    Terapia pierwszego rzutu u pacjentów z zaawansowanym rakiem dróg żółciowych (BTC)
    E.1.1.1Medical condition in easily understood language
    First Line biliary tract cancers (BTC)
    Terapia pierwszego rzutu w zaawansowanym raku dróg żółciowych (BTC)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 27.0
    E.1.2Level PT
    E.1.2Classification code 10008593
    E.1.2Term Cholangiocarcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy of Arm A compared to Arm B in terms of OS in patients with first-line advanced BTC
    Ocena skuteczności leczenia w grupie A w porównaniu z grupą B pod względem czasu przeżycia (OS) u pacjentów z zaawansowanym BTC w leczeniu pierwszego rzutu
    E.2.2Secondary objectives of the trial
    To further assess the efficacy of Arm A compared to Arm B in terms of Progression-free survival (PFS), ORR (Objective response rate) , and Duration of response (DoR) in patients with first-line advanced BTC using Investigator assessments

    To summarize the efficacy of Arm A compared to Arm B in terms of ORR and DoR in patients with first-line advanced BTC using BICR
    assessments

    To assess disease-related symptoms, impacts, and HRQoL in patients treated with Arm A compared to Arm B

    To assess the efficacy of Arm A compared to Arm B by PD-L1 expression

    To assess the PK of durvalumab when used in combination with gemcitabine/cisplatin

    To investigate the immunogenicity of durvalumab
    1. Dodatkowa ocena skuteczności leczenia w grupie A w porównaniu z grupą B pod względem czasu przeżycia bez progresji choroby (PFS), odsetka odpowiedzi obiektywnych (ORR) i czasu trwania odpowiedzi (DoR) u pacjentów z zaawansowanym BTC w leczeniu pierwszego rzutu na podstawie oceny badacza;
    2. Podsumowanie skuteczności leczenia w grupie A w porównaniu z grupą B pod względem ORR i DoR u pacjentów z zaawansowanym BTC w leczeniu pierwszego rzutu na podstawie oceny BICR;
    3. Ocena objawów związanych z chorobą, skutków leczenia oraz jakości życia uwarunkowanej stanem zdrowia (HRQoL) u pacjentów leczonych w grupie A w porównaniu z grupą B;
    4. Ocena skuteczności leczenia w grupie A w porównaniu z grupą B na podstawie ekspresji PD¬L1;
    5. Ocena farmakokinetyki durwalumabu stosowanego w skojarzeniu z gemcytabiną/cisplatyną;
    6. Ocena immunogenności durwalumabu;
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion
    1. Histologically confirmed, unresectable advanced or metastatic biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma.
    2. Previously untreated disease if unresectable or metastatic at initial diagnosis
    3. Recurrent disease >6 months after curative surgery or >6 months after the completion of adjuvant therapy (chemotherapy and/or radiation)
    4. WHO/ECOG PS of 0 or 1
    1. Potwierdzony histologicznie, nieoperacyjny zaawansowany lub przerzutowy gruczolakorak dróg żółciowych, w tym rak przewodów żółciowych (wewnątrzwątrobowych lub zewnątrzwątrobowych) i rak pęcherzyka żółciowego;
    2. Do udziału w badaniu będą się kwalifikować pacjenci z nieleczonym wcześniej nowotworem, jeśli jest on nieoperacyjny lub przerzutowy w chwili postawienia początkowego rozpoznania;
    3. Do udziału w badaniu będą się kwalifikować pacjenci, u których doszło do nawrotu choroby >6 miesięcy po radykalnej operacji chirurgicznej oraz >6 miesięcy po zakończeniu leczenia adiuwantowego (chemioterapii i/lub radioterapii), o ile to ostatnie zostanie zastosowane;
    4. Stan sprawności wg skali Światowej Organizacji Zdrowia (WHO)/Eastern Cooperative Oncology Group (ECOG) 0 lub 1 w chwili kwalifikacji do udziału w badaniu;
    E.4Principal exclusion criteria
    Exclusion
    1. History of another primary malignancy
    2. Brain metastases or spinal cord compression
    3. Uncontrolled intercurrent illness
    4. Major surgical procedure within 28 days prior to the study
    5. Prior locoregional therapy such as radioembolization
    1. Inny pierwotny nowotwór złośliwy w wywiadzie;
    2. Przerzuty do mózgu lub ucisk na rdzeń kręgowy;
    3. Niekontrolowane choroby współistniejące;
    4. Poważna operacja chirurgiczna (w ocenie badacza) w okresie 28 dni przed przyjęciem pierwszej dawki produktu badanego;
    5. Przebyte leczenie lokoregionalne, takie jak radioembolizacja;
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival
    Przeżycie całkowite
    E.5.1.1Timepoint(s) of evaluation of this end point
    Assessments for Overall survival will be collected regularly at predefined time points until death
    Ocena przeżycia całkowitego będzie prowadzona regularnie zgodnie z określonym terminarzem do odnotowania zgonu
    E.5.2Secondary end point(s)
    Progression-free survival (PFS), ORR (Objective response rate) , and Duration of response (DoR) according to RECIST 1.1using Investigator assessments

    ORR and DoR according to RECIST 1.1 using BICR assessments

    EORTC QLQ-C30: Global health status/QoL and impacts (eg, physical function); multi-term symptoms (eg, fatigue); and single items (eg, appetite loss, insomnia). EORTC QLQ-BIL21: Single-item symptoms (eg, abdominal pain [item 42], pruritus [item 36], jaundice [item 35])

    Association of PD-L1 expression level with PFS, ORR, DoR, and DCR (Disease control rate) according to RECIST 1.1 using Investigator assessments and OS (Overall survival)

    Serum concentration of durvalumab (peak and trough concentrations)

    Presence of ADAs for durvalumab (confirmatory results: positive or negative)
    PFS, ORR i DoR wg kryteriów RECIST 1.1 na podstawie oceny badacza

    ORR i DoR wg kryteriów RECIST 1.1 na podstawie oceny BICR

    Kwestionariusz EORTC QLQ C30: ogólny stan zdrowia/QoL i skutki leczenia (np. wpływ na sprawność fizyczną); objawy określane przy użyciu kilku terminów (np. zmęczenie) i pojedyncze pozycje (np. zanik łaknienia, bezsenność); EORTC QLQ-BIL21: objawy stanowiące pojedyncze pozycje (np. bóle brzucha [pozycja 42], świąd [pozycja 36], żółtaczka [pozycja 35])

    Związek poziomu ekspresji PD-L1 z PFS, ORR, DoR i DCR wg kryteriów RECIST 1.1, z uwzględnieniem ocen badacza i OS

    Stężenie durwalumabu w surowicy (wartości maksymalne i minimalne)

    Obecność ADA przeciwko durwalumabowi (wyniki potwierdzające: dodatnie lub ujemne)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Assessments will be made regularly until progressive disease or until the end of the study
    Ocena będzie prowadzona regularnie do wystąpienia progresji choroby lub zakończenia badania
    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 No
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA37
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Chile
    Hong Kong
    Taiwan
    China
    India
    Japan
    Korea, Republic of
    Russian Federation
    Thailand
    United Kingdom
    United States
    Bulgaria
    France
    Italy
    Poland
    Türkiye
    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
    Last expected visit/contact of last patient undergoing the study
    Ostatnia planowa wizyta/kontakt z ostatnim pacjentem uczestniczącym w badaniu
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months4
    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: 405
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 405
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state45
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 125
    F.4.2.2In the whole clinical trial 810
    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)
    The study will continue approximately 40 months after FSI and if the patients who continue to receive benefit from their assigned treatment at the final data cut-off and database closure may continue to receive their assigned treatment at the investigator's and patient's discretion.
    Badanie będzie trwało ok. 40 miesięcy od daty włączenia pierwszego pacjenta i jeżeli pacjenci będą nadal odnosi korzyść z otrzymywanego leczenia w chwili odcięcia danych i zamknięcia bazy danych, mogą oni on kontynuować przypisane im leczenie według uznania Badacza i pacjenta.
    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 Decision2019-07-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-05-23
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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