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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   41449   clinical trials with a EudraCT protocol, of which   6808   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).

    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
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    EudraCT Number:2018-004758-39
    Sponsor's Protocol Code Number:ESR-18-13485
    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:2021-06-17
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-004758-39
    A.3Full title of the trial
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberESR-18-13485
    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.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.4.1Name of organisation providing supportAUSL della Romagna
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIRST IRCCS
    B.5.2Functional name of contact pointCentro di Coordinamento Studi Clini
    B.5.3 Address:
    B.5.3.1Street AddressVia P. Maroncelli 40
    B.5.3.2Town/ cityMeldola
    B.5.3.3Post code47014
    B.5.4Telephone number0544285813
    B.5.5Fax number0544285330
    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 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 nameanti-PD-L1 monoclonal antibody
    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. cell therapy medicinal product Information not present in EudraCT
    D. therapy medical product Information not present in EudraCT
    D. Engineered Product Information not present in EudraCT
    D. ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D. 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
    Locally advanced (T3-4 N0-1) rectal cancer.
    Carcinoma del retto localmente avanzato, T3-4 e N0-1.
    E.1.1.1Medical condition in easily understood language
    Rectal cancer
    Tumore del retto
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10038019
    E.1.2Term Rectal adenocarcinoma
    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
    Determine the pathological complete response rate (pCR) in patients with rectal cancer treated with standard neo-adjuvant chemotherapy with capecitabine and radiation followed by durvalumab and surgery.
    Determinare il tasso di risposta patologica completa (pCR) in pazienti con carcinoma rettale trattati con chemioradioterapia neoadiuvante standard con capecitabina e radioterapia seguita da durvalumab e chirurgia.
    E.2.2Secondary objectives of the trial
    1. Determine safety of treatment with durvalumab;
    2. Determine clinical complete remission rate (cCR) after durvalumab treatment, before surgery;
    3. Determine disease-free survival (DFS).
    1.Determinare la sicurezza del trattamento con durvalumab;
    2.Determinare il tasso di remissione clinica completa (cCR) dopo il trattamento con durvalumab, prima dell'intervento chirurgico;
    3.Determinare la sopravvivenza libera da malattia (DFS).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. 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 Data Privacy Directive obtained from the patient/legal representative prior to performing any protocol- related procedures, including screening evaluations.
    2. Age > 18 years at time of study entry.
    3. Eastern Cooperative Oncology Group (ECOG) 0 or 1.
    4. Histological diagnosis of adenocarcinoma of rectum.
    5. Clinical stage 2-3 rectal adenocarcinoma, cT3/4N0/M0 or Tx N1-2/M0, assessed by thorax abdomen pelvis with contrast Computed tomography (CT) scan, pelvi Magnetic resonance imaging (MRI) scan, pancolonscopy.
    6. Able to swallow oral medication.
    7. Body weight >30kg.
    8. Adequate normal organ and marrow function as defined below:
    • Haemoglobin =9.0 g/dL
    • Absolute neutrophil count (ANC) > 1500 per mm3
    • Platelet count >100.000 per mm3
    • 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 haemolysis 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
    • Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976).

    9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre- menopausal patients. Women of childbaring potential or male patients with a female partner of childbearing potential must agree to use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (90 days after the last dose of durvalumab monotherapy) as detailed in section 7.1. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:

    • Women <50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post- menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
    • Women =50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

    10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
    11. Must have a life expectancy of at least 12 weeks.
    . Esser in grado di esprimere il proprio consenso informato firmato che include il rispetto dei requisiti e delle restrizioni elencate nel modulo di consenso informato (ICF) e nel presente protocollo. Consenso informato scritto e direttiva sulla privacy dei dati ottenuti dal paziente/rappresentante legale prima di eseguire qualsiasi procedura relativa al protocollo, comprese le valutazioni di screening.
    2. Età = 18 anni al momento dell'ingresso nello studio.
    3. Eastern Cooperative Oncology Group (ECOG) 0 o 1.
    4. Diagnosi istologica dell'adenocarcinoma del retto.
    5. Stadio clinico II-III di adenocarcinoma rettale, cT3/4N0/M0 o Tx N1-2/M0, valutato mediante tomografia computerizzata (CT), risonanza magnetica pelvi (MRI), pancolonscopia.
    6. Il paziente riesce ad assumere farmaci per via orale.
    7. Peso corporeo >30 kg.
    8. Adeguata funzionalità midollare, epatica e renale come di seguito definito:
    • emoglobina = 9g/dL
    • conta assoluta neutrofili = 1500/mm2
    • conta piastrinica =100000/mm2
    • bilirubina sierica = 1.5 * valore massimo normale secondo gli standard del laboratorio del centro. Questo criterio non si applica a pazienti con confermata sindrome di Gilbert (iperbilirubinemia persistente o ricorrente, non coniugata, in assenza di emolisi o patologia epatica), che saranno ammessi allo studio esclusivamente previo consulto con il Medico di Medicina Generale
    • AST (SGOT)/ALT(SGPT) = 2.5 * valore massimo normale secondo gli standard del laboratorio del centro
    • clearance della creatinina (CL) misurata > 40 mL/min o CL calcolata > 40 mL/min secondo la formula Cockcroft-Gault (Cockcroft and Gault 1976).
    9. Paziente in post-menopausa o con test di gravidanza (urinario o sierologico) negativo per pazienti di sesso femminile in pre-menopausa.
    Donne in età fertile o uomini con partner femminile in età fertile devono acconsentire ad utilizzare almeno un metodo contraccettivo ad alta efficacia dal momento dello screening e durante la durata complessiva del trattamento farmacologico e del periodo di washout del farmaco (90 giorni dopo l’ultima dose di durvalumab in monoterapia), come dettagliato nella sezione 7.1 del protocollo.
    Le donne verranno considerate in post-menopausa se in amenorrea da 12 mesi senza alternativa causa medica. Si applicano inoltre i seguenti requisiti specifici per l’età:
    • donne in età < 50 anni saranno considerate in post-menopausa se in amenorrea per almeno 12 mesi in seguito alla cessazione di trattamenti ormonali esogeni e se hanno livelli di ormone luteinizzante o follicolo-stimolante all’interno dell’intervallo considerato di post-menopausa secondo gli standard del laboratorio del centro, o se hanno subìto ooforectomia bilaterale o isterectomia.
    • donne in età = 50 anni saranno considerate in post-menopausa se in amenorrea per almeno 12 mesi in seguito alla cessazione di trattamenti ormonali esogeni, se sono state indotte in menopausa da radioterapia con l’ultima mestruazione di almeno un anno precedente l’inizio dello studio, o se sono state sterilizzate chirurgicamente (ooforectomia bilaterale, salpingectomia bilaterale o isterectomia).
    10. Il paziente è in grado di seguire il protocollo per l’intera durata dello studio, inclusi il trattamento in corso, le visite programmate, gli esami e il follow up.
    11. L’aspettativa di vita deve essere di almeno 12 settimane.
    E.4Principal exclusion criteria
    Exclusion Criteria:

    1. Previous treatment for local advanced rectum cancer.
    2. Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
    3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
    4. History of hypersensitivity to fluorouracil.
    5. Known Dihydropyrimidine dehydrogenase (DPD) deficiency.
    6. History of another primary malignancy except for:

    - Malignancy treated with curative intent and with no known active disease =5 years before the first dose of study drug and of low potential risk for recurrence
    - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    - Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ

    7. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at

    physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. 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)

    8. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
    9. Major surgical procedure within 28 days prior to the first dose of treatment.
    10. Uncontrolled intercurrent illness
    Precedente trattamento per carcinoma rettale localmente avanzato
    2. Arruolamento concomitante in un altro studio clinico a meno che non sia osservazionale (non interventistico) o durante il follow up di uno studio interventistico.
    3. Precedente trattamento con inibitori di PD1 o PD-L1, incluso il durvalumab.
    4. Ipersensibilità al fluoro uracile.
    5. Noto deficit della diidropirimidina deidrogenasi.
    6. Altro tumore primario, eccetto:
    • Tumore trattato con intento curatico e con nota inattività per = 5 anni prima della prima dose di farmaco in studio e che basso rischio di recidiva
    • Tumore cutaneo (non melanoma) adeguatamente trattato, senza evidenza di malattia
    • Carcinoma in situ adeguatamente trattato senza evidenza di malattia (es. carcinoma cervicale in situ).
    7. Utilizzo concomitante o precedente di farmaci immunosoppressivi nei 14 giorni antecedenti la prima dose di durvalumab, con l’eccezione di trattamento intranasale o inalatorio di corticosteroidi o corticosteroidi per via sistemica a dosi fisiologiche (= 10 mg/die di prednisone o equivalente corticosteroide). Fanno eccezione:
    • Steroidi per via intranasale, inalatoria, topica o iniezioni locali (es. iniezioni intra-articolari)
    • Corticosteroidi per via sistemica a dosi fisiologiche (= 10 mg/die di prednisone o equivalente corticosteroide)
    • Steroidi come prevenzione per reazioni di ipersensibilità
    8. Qualunque chemioterapia concomitante, sperimentale, biologica, o trattamento ormonale antitumorale. Il trattamento concomitante di tipo ormonale per patologie non correlate a tumore (es. terapia ormonale sostitutiva) è accettabile.
    9. Interventi di chirurgia maggiore entro 28 giorni dall’inizio del trattamento.
    10. presenza di patologie concomitanti non controllate
    E.5 End points
    E.5.1Primary end point(s)
    proportion of patients with complete pathological response and corresponding confidence intervals after durvalumab treatment.
    proporzione di pazienti con risposta patologica completa e corrispondenti intervalli di confidenza in seguito a trattamento con durvalumab.
    E.5.1.1Timepoint(s) of evaluation of this end point
    18 months after study start
    A 18 mesi dall'apertura dello studio
    E.5.2Secondary end point(s)
    Determine safety of treatment with durvalumab in terms of number and the percentage of patients with every type of event; proportion of patients with complete clinical response and corresponding confidence intervals after durvalumab treatment.; DFS is defined as time since surgery until disease occurrence or death, whichever occur first, or last follow-up and will be estimated by using Kaplan-Meier approach
    Sicurezza del trattamento con durvalumab in termini di numero e percentuale di pazienti per i quali si verificano eventi avversi; proporzione di pazienti con risposta clinica completa e corrispondenti intervalli di confidenza in seguito a trattamento con durvalumab.; La sopravvivenza libera da malattia, definita come il tempo trascorso dall'intrvento a ripresa di malattia, decesso o ultimo follow up; verrà stimata utilizzando il metodo Kaplan-Meier
    E.5.2.1Timepoint(s) of evaluation of this end point
    After 21 months from study start; 18 months after study start; 6 years
    After 21 mesi dall'apertura dello studio; A 18 mesi dall'apertura dello studio; 6 anni
    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 No
    E.6.4Safety No
    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. 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 Yes
    E. trial design description
    singolo braccio
    single arm
    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 concerned7
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    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 years6
    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: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 60
    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)
    Follow-up visit every 4 months after surgery (first 2 years), then every 6 months (next 3 years).
    Complete physical exam, digital rectal examination; vital signs, weight; Clinical laboratory tests. Thorax abdomen pelvis CT every 4 months after surgery (first 2 years), then every 6 months (next 3 years).
    Sigmoidoscopy every 6 months after surgery (first 2 years). Pancolonscopy at 1 year after surgery, then 3 years and finally every 5 years (with no colon lesions).
    Visite di follow-up verranno effettuate ogni 4 mesi dopo la chirurgia per due anni e poi ogni 6 mesi per i successivi 3 anni. Durante le visite saranno effettuati:
    - esame obiettivo, con esplorazione rettale
    - esami di laboratorio
    - rivalutazioni strumentali (CT scan).
    La sigmoidoscopia verrà effettuata ogni 6 mesi per i primi due anni. L'estensione a pancolonscopia verrà effettuata dopo 1 anno dall'intervento, dopo 3 anni e successivamente ogni 5 anni in assenza di lesioni al colon.
    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 Decision2019-05-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-12
    P. End of Trial
    P.End of Trial StatusOngoing
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