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    Summary
    EudraCT Number:2023-000138-13
    Sponsor's Protocol Code Number:CITATION
    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:2023-01-31
    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 number2023-000138-13
    A.3Full title of the trial
    Neo-adjuvant Chemo and immunotherapy with durvalumab (MEDI4736) and tremelimumab (MEDI1123) In The pre-operAtive Treatment of locally advanced cholangIOcarciNoma: an exploratory and translational study. CITATION study
    STUDIO CITATION -Studio multicentrico, interventistico, prospettico, farmacologico su chemio e immunoterapia neo- adiuvanti con durvalumab e tremelimumab nel trattamento preoperatorio del Colangiocarcinoma localmente avanzato: uno studio esploratorio traslazionale.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Neo-adjuvant Chemo and immunotherapy with durvalumab (MEDI4736) and tremelimumab (MEDI1123) In The pre-operAtive Treatment of locally advanced cholangIOcarciNoma: an exploratory and translational study. CITATION study
    Studio multicentrico, interventistico, prospettico, farmacologico su chemio e immunoterapia neo- adiuvanti con durvalumab e tremelimumab nel trattamento preoperatorio del Colangiocarcinoma localmente avanzato: uno studio esploratorio traslazionale. STUDIO CITATION.
    A.3.2Name or abbreviated title of the trial where available
    CITATION
    CITATION
    A.4.1Sponsor's protocol code numberCITATION
    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 SponsorISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstraZeneca S.p.A.
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI FONDAZIONE “G. PASCALE”
    B.5.2Functional name of contact pointTerapie Innova Metastasi Addominale
    B.5.3 Address:
    B.5.3.1Street Addressvia mariano Semmola
    B.5.3.2Town/ cityNapoli
    B.5.3.3Post code80131
    B.5.3.4CountryItaly
    B.5.4Telephone number08117770344
    B.5.5Fax number08117770344
    B.5.6E-maila.ottaiano@istitutotumori.na.it
    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 nameTremelimumab
    D.3.2Product code [Tremelimumab]
    D.3.4Pharmaceutical form Concentrate 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.3.9.1CAS number 745013-59-6
    D.3.9.2Current sponsor codeTremelimumab
    D.3.9.3Other descriptive nameTremelimumab
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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 RoleComparator
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameGemcitabina
    D.3.2Product code [Gemcitabina]
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeGEMCITABINA
    D.3.9.3Other descriptive nameGEMCITABINA
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    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: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameCisplatino
    D.3.2Product code [Cisplatino]
    D.3.4Pharmaceutical form Concentrate 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 INNcisplatino
    D.3.9.2Current sponsor codecisplatino
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    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: 4
    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 Yes
    D.2.1.1.1Trade name IMFINZI - 50 MG/ML - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) 10 ML - 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderASTRAZENECA AB
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 [DURVALUMAB]
    D.3.4Pharmaceutical form Concentrate 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.3.9.2Current sponsor codeDURVALUMAB
    D.3.9.3Other descriptive nameDURVALUMAB
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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
    Locally advanced cholangiocarcinoma patients
    Pazienti affetti da CCA localmente avanzato
    E.1.1.1Medical condition in easily understood language
    Locally advanced cholangiocarcinoma patients
    Pazienti affetti da CCA localmente avanzato
    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 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 No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary Objectives:
    To determine whether neoadjuvant chemo- and immunotherapy decrease the recurrence rate of CCA at 12 months after surgery.
    Obiettivo primario: determinare se la chemio e l'immunoterapia neoadiuvanti riducono le recidive di CCA a 12 mesi dopo l'intervento chirurgico.
    E.2.2Secondary objectives of the trial
    Secondary Objectives: Rate of R0 resections, radiologic and pathologic responses, toxicity and overall survival.
    Obiettivi secondari: valutare il tasso di resezioni R0, le risposte radiologiche e patologiche, la tossicità e la sopravvivenza globale.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
    • Histologically or pathologically confirmed CCA.
    • Age >18 years at time of study entry.
    • Eastern Cooperative Oncology Group (ECOG) 0 or 1.
    • Locally advanced disease (as assessed in multidisciplinary sessions).
    • Life expectancy of at least 16 weeks.
    • Body weight >30 kg
    • Adequate normal organ and marrow function as defined below: Haemoglobin =9.0 g/dL
    • Absolute neutrophil count (ANC =1.5 × 109 /L)
    • Platelet count =100 × 109/L
    • Serum bilirubin =1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
    • AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN
    • Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
    • At least 1 lesion that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization.
    No previous systemic or local treatments including radiation therapy, radiofrequency ablations, electro-chemotherapy.
    - Capacità di fornire un consenso informato firmato che includa il rispetto dei requisiti e delle restrizioni elencate nel modulo di consenso informato nel presente protocollo.
    - Consenso informato scritto e qualsiasi autorizzazione richiesta a livello locale (Direttiva sulla privacy dei dati dell'Unione europea) ottenuti dal paziente/rappresentante legale prima di eseguire qualsiasi procedura relativa al protocollo, incluso valutazioni di screening.
    - CCA cito- o istologicamente confermato.
    - Età >18 anni al momento dell'ingresso nello studio.
    - PS ECOG 0 o 1.
    - Malattia localmente avanzata (valutata in sessioni multidisciplinari).
    - Aspettativa di vita di almeno 16 settimane.
    - Peso corporeo >30 kg
    - Adeguata funzione degli organi e del midollo come definita di seguito:
    - Emoglobina =9,0 g/Dl
    - Conta assoluta dei neutrofili (ANC =1,5 × 109 /L)
    - Conta piastrinica =100 × 109/L
    - Bilirubina sierica =1,5 volte rispetto al limite superiore della norma istituzionale (ULN). Ciò non si applica ai pazienti con sindrome di Gilbert confermata (iperbilirubinemia persistente o ricorrente che è prevalentemente non coniugata in assenza di emolisi o patologia epatica), che saranno ammessi solo in consultazione con il proprio medico.
    - AST (SGOT)/ALT (SGPT) =2,5 x limite superiore istituzionale della norma a meno che non siano presenti metastasi epatiche, nel qual caso deve essere =5x ULN
    - Clearance della creatinina (CL) misurata >40 ml/min o Clearance della creatinina calcolata CL>40 ml/min mediante la formula di Cockcroft-Gault (Cockcroft e Gault 1976) o mediante la raccolta delle urine delle 24 ore per la determinazione della clearance della creatinina.
    - Almeno 1 lesione target secondo RECIST 1.1 al basale. La valutazione del tumore mediante tomografia computerizzata (TC) o risonanza magnetica (MRI) deve essere eseguita entro 28 giorni prima della randomizzazione.
    - Nessun precedente trattamento sistemico o locale incluso radioterapia, ablazione con radiofrequenza, e/o elettro-chemioterapia.
    E.4Principal exclusion criteria
    • Any previous participation in another clinical interventional study.
    • Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
    • History of allogenic organ transplantation.
    • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, interstitial lung disease, etc.]). The following are exceptions to this criterion:
    a. Patients with vitiligo or alopecia
    b. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
    c. Any chronic skin condition that does not require systemic therapy
    d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician
    e. Patients with celiac disease controlled by diet alone
    • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, history of myocardial infarction within 12 months, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
    • History of bowel obstruction, refractory ascites, or bowel perforation due to advanced disease within the past 3 months from start of study treatment.
    • Significant bleeding diathesis or coagulopathy. Serious, nonhealing wound, ulcer, or current healing fracture.
    • History of another primary malignancy except for
    a. Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence
    b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    c. Adequately treated carcinoma in situ without evidence of disease
    • History of leptomeningeal carcinomatosis
    • Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
    • History of active primary immunodeficiency.
    • Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
    • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
    • Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
    • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
    • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or180 days after the last dose of durvalumab and tremelimumab combination therapy.
    • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
    - Qualsiasi precedente partecipazione ad un altro studio clinico interventistico.
    - L'uso simultaneo della terapia ormonale per condizioni non correlate al cancro (ad es. terapia ormonale sostitutiva) è accettabile.
    - Storia di trapianto allogenico di organi.
    - Disturbi autoimmuni o infiammatori attivi o precedentemente documentati (tra cui malattie infiammatorie intestinali [ad es. colite o morbo di Crohn], diverticolite [ad eccezione della diverticolosi], lupus eritematoso sistemico, sindrome da sarcoidosi o sindrome di Wegener [granulomatosi con poliangioite, morbo di Graves, artrite reumatoide, ipofisite, uveite, malattia polmonare interstiziale, ecc.]). Fanno eccezione a questo criterio:
    a. Pazienti con vitiligine o alopecia;
    b. Pazienti con ipotiroidismo (ad es. in seguito alla sindrome di Hashimoto) stabile alla sostituzione ormonale;
    c. Qualsiasi condizione cronica della pelle che non richieda una terapia sistemica;
    d. I pazienti senza malattia attiva negli ultimi 5 anni possono essere inclusi ma solo dopo aver consultato il medico dello studio;
    e. Pazienti celiaci controllati dalla sola dieta.
    - Malattie intercorrenti non controllate, incluse, a titolo esemplificativo ma non esaustivo, infezione in corso o attiva, insufficienza cardiaca congestizia sintomatica, ipertensione non controllata, angina pectoris instabile, storia di infarto del miocardio entro 12 mesi, aritmia cardiaca, malattia polmonare interstiziale, gravi condizioni gastrointestinali croniche associate a diarrea, o malattie psichiatriche/situazioni sociali che limiterebbero il rispetto dei requisiti dello studio, aumenterebbero sostanzialmente il rischio di incorrere in eventi avversi o comprometterebbero la capacità del paziente di fornire il consenso informato scritto
    - Storia di ostruzione intestinale, ascite refrattaria o perforazione intestinale dovuta a malattia avanzata negli ultimi 3 mesi dall'inizio del trattamento in studio.
    - Significativa diatesi emorragica o coagulopatia. Ferita, ulcera o frattura in via di guarigione grave, non cicatrizzante.
    - Storia di un altro tumore maligno primario eccetto per
    a. Malignità trattata con intento curativo e senza malattia attiva nota =5 anni prima della prima dose di IP e con basso rischio potenziale di recidiva;
    b. Cancro cutaneo non melanoma o lentigo maligna adeguatamente trattati senza evidenza di malattia;
    c. Carcinoma in situ adeguatamente trattato senza evidenza di malattia.
    - Storia di carcinomatosi leptomeningea
    - Metastasi cerebrali o compressione del midollo spinale. I pazienti con sospette metastasi cerebrali allo screening devono sottoporsi a una risonanza magnetica (preferibile) o TC, ciascuna preferibilmente con mezzo di contrasto cerebrale IV prima dell'ingresso nello studio.
    - Storia di immunodeficienza primaria attiva.
    - Infezione nota da epatite attiva, anticorpi positivi per il virus dell'epatite C (HCV), antigene di superficie del virus dell'epatite B (HBV) (HBsAg) o anticorpi core dell'HBV (anti-HBc), allo screening. Sono idonei i partecipanti con un'infezione da HBV passata o risolta (definita come la presenza di anti HBc e l'assenza di HBsAg). I partecipanti positivi all'anticorpo dell'HCV sono idonei solo se la reazione a catena della polimerasi è negativa per l'RNA dell'HCV.
    - Noto per essere risultato positivo al virus dell'immunodeficienza umana (HIV) (anticorpi HIV 1/2 positivi) o infezione attiva da tubercolosi (valutazione clinica che può includere anamnesi, esame obiettivo e risultati radiografici, o test della tubercolosi in linea con la pratica locale).
    - Uso attuale o precedente di farmaci immunosoppressori entro 14 giorni prima della prima dose di durvalumab o tremelimumab. Fanno eccezione a questo criterio:
    - Steroidi intranasali, inalatori, topici o iniezioni locali di steroidi (ad es. iniezione intraarticolare);
    - Corticosteroidi sistemici a dosi fisiologiche non superiori a <<10 mg/die>> di prednisone o suo equivalente;
    - Steroidi come premedicazione per reazioni di ipersensibilità (ad es. premedicazione con scansione TC);
    - Ricezione di vaccino vivo attenuato entro 30 giorni prima della prima dose di IP.
    - Pazienti di sesso femminile in gravidanza o in allattamento o pazienti di sesso maschile o femminile in età riproduttiva che non sono disposti a utilizzare un controllo delle nascite efficace dallo screening fino a 90 giorni dopo l'ultima dose di durvalumab in monoterapia o 180 giorni dopo l'ultima dose di durvalumab e la terapia di combinazione di tremelimumab.
    - Allergia o ipersensibilità nota all'IP o a qualsiasi eccipiente dei farmaci in studio.
    E.5 End points
    E.5.1Primary end point(s)
    12-month survival after surgery
    sopravvivenza a 12 mesi dopo intervento chirurgico
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 month
    12 mesi
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned6
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial 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
    LVLP
    LVLP
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    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 years2
    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: 26
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 12
    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 state38
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 38
    F.4.2.2In the whole clinical trial 38
    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)
    none
    nessuno
    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 Decision2023-04-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-04-05
    P. End of Trial
    P.End of Trial StatusOngoing
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