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    Summary
    EudraCT Number:2017-003582-10
    Sponsor's Protocol Code Number:AVANA
    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
    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 number2017-003582-10
    A.3Full title of the trial
    PHASE II STUDY OF PREOPERATIVE CHEMORADIOTHERAPY PLUS AVELUMAB IN PATIENTS WITH LOCALLY ADVANCED RECTAL CANCER
    STUDIO DI FASE II DI CHEMIORADIOTERAPIA PREOPERATORIA IN ASSOCIAZIONE AD AVELUMAB IN PAZIENTI CON CARCINOMA RETTALE LOCALMENTE AVANZATO
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Chemoradiotherapy plus avelumab in locally advanced rectal cancer
    Chemioradioterapia preoperatoria più avelumab su carcinoma rettale localmente avanzato
    A.3.2Name or abbreviated title of the trial where available
    AVANA
    AVANA
    A.4.1Sponsor's protocol code numberAVANA
    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 SponsorG.O.N.O. - GRUPPO ONCOLOGICO DEL NORD OVEST
    B.1.3.4Country
    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 supportFondazione GONO
    B.4.2CountryItaly
    B.4.1Name of organisation providing supportMerck KgaA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPoliclinico Universitario A. Gemelli
    B.5.2Functional name of contact pointOncologia Medica
    B.5.3 Address:
    B.5.3.1Street AddressL.go Agostino Gemelli
    B.5.3.2Town/ cityRoma
    B.5.3.3Post code00168
    B.5.3.4CountryItaly
    B.5.4Telephone number0630154844
    B.5.5Fax number0635502775
    B.5.6E-mailavanastudy@gmail.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 nameAvelumab
    D.3.2Product code [EU/1/17/1214/001]
    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 INNavelumab
    D.3.9.1CAS number 1537032-82-8
    D.3.9.2Current sponsor codeAvelumab
    D.3.9.3Other descriptive nameAvelumab is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). It is a fully human anti-PD immunoglobulin G1 (IgG1) lambda monoclonal antibody with antineoplastic actions
    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
    Locally advanced rectal cancer
    Carcinoma Rettale Localmente Avanzato
    E.1.1.1Medical condition in easily understood language
    Locally advanced rectal tumor
    Tumore del retto 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 10038038
    E.1.2Term Rectal 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
    Evaluate the rate of complete pathologic response (pCR)
    Valutazione del tasso di risposte patologiche complete
    E.2.2Secondary objectives of the trial
    R0 resection rate; Tumor downstaging; Local recurrence; Sphincter preservation rate; Progression-free survival (PFS); Overall survival (OS); Safety profile; Evaluation of exploratory predictive and/or prognostic biomarkers.
    Tasso di resezioni R0; Downstaging tumorale; Recidiva locale; Tasso di preservazione dello sfintere; Sopravvivenza libera da progressione; Sopravvivenza globale; Profilo di sicurezza; Valutazione di potenziali biomarcatori predittivi e/o prognostici.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Locally advanced, resectable disease defined by the presence of at least one of the following features:
    cN+, cT4, high risk cT3 (according to magnetic resonance imaging [MRI] criteria);
    distal tumor margin at < 12 cm from the anal verge;
    no evidence of metastatic disease by computed tomography (CT) scan of the chest and abdomen and total body FDG-PET/CT scan;
    tumor must be amenable to curative resection;
    no history of invasive rectal malignancy;
    no other rectal cancers (i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, or cloacogenic carcinoma) or synchronous colon cancer;
    available tumor samples at baseline (archival biopsy) and after chemoradiotheraphy + avelumab.
    Tumore del retto localmente avanzato, resecabile, con almeno una delle seguenti caratteristiche:
    cN+, cT4, cT3 alto rischio (secondo i criteri RM);
    margine distale del tumore <12 cm dal margine anale;
    no evidenza di metastasi alla TC torace/addome e alla PET;
    tumore resecabile in modo radicale;
    no storia di tumori maligni rettali;
    no tumori del retto di altri istotipi (sarcoma, linfoma, carcinoide, carcinoma a cellule squamose o carcinoma cloacogenico) o tumore sincrono del colon;
    disponibilita’ del campione tumorale basalmente e dopo chemioradioterapia + avelumab.
    E.4Principal exclusion criteria
    Previous therapy with any antibody or drug targeting T cell coregulatory proteins, or immunosuppressive agents;
    previous pelvic RT;
    active autoimmune disease;
    current use of immunosuppressive medication, EXCEPT for the following: a. Intranasal, inhaled, topical steroids, or local steroids injection (e.g. intra- articular injection); b. Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent, steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication);
    prior organ transplantation;
    known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
    hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening;
    vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
    Precedenti terapie con farmaci anti-cellule T o terapie immunosoppressive;
    precedente RT pelvica;
    malattia autoimmune attiva;
    terapia immunosoppressiva in corso, fatta eccezione per steroidi intranasali, inalatori o topici, iniezione locale di steroidi (es iniezione intrarticolare), corticosteroidi sistemici alla dose fisiologica =10 mg/die di
    prednisone o equivalente, premedicazione con steroidi per reazioni di ipersensibilita’ (es premedicazione per il mdc della TC);
    precedente trapianto d’organo;
    storia di HIV o AIDS;
    infezione di epatite B o C allo screening;
    vaccino entro 4 settimane prima dell’ inizio di avelumab o durante il trattamento, fatta eccezione per vaccini inattivati.
    E.5 End points
    E.5.1Primary end point(s)
    Pathologic Complete Response (pCR) Rate.
    pCR rate is defined as the percentage of patients, relative to the total of enrolled subjects, achieving complete histological regression with no available tumor cells yT0N0 (a central pathology review will be performed at Istituto Nazionale Tumori di Milano).
    Tasso di risposta completa patologica (pCR).
    Il tasso di pCR è definito come percentuale di pazienti, rispetto al totale dei soggetti arruolati, in grado di ottenere una completa regressione istologica senza cellule tumorali disponibili yT0N0 (una revisione centralizzata sarà eseguita presso l'Istituto Nazionale Tumori di Milano).
    E.5.1.1Timepoint(s) of evaluation of this end point
    48 month
    48 mesi
    E.5.2Secondary end point(s)
    R0 Resection Rate.
    R0 Resection Rate is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing R0 resection of primary tumour. R0 surgery is defined as microscopically margin free complete surgical removal of disease.; Tumor downstaging.
    Tumour downstaging is defined as reduction of at least one level in T or N staging between the baseline MRI and histopathological staging, without evidence of upstaging or disease progression.; Local recurrence.
    Local recurrence is defined as an intrapelvic recurrence following a primary rectal cancer resection, with or without distal metastasis.; Sphincter preservation rate.
    Sphincter preservation rate is defined as the percentage of patients undergoing sphincter-sparing surgery.; Progression Free Survival (PFS).
    PFS is defined as the time between treatment start and one of the following events: non-radical surgery of the primary tumour (R2 resection), locoregional recurrence after R0/1 resection of the primary tumour, metastatic disease or progression, or death from any cause, whichever occurred first. The determination of disease progression will be based on investigator-reported measurements. Patients who are alive without having one of the above events at the end of the study will be censored at their last radiological assessment.; Overall Survival (OS).
    OS is defined as the time from treatment start to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.; Safety profile.
    Overall Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0, during the preoperative and postoperative phases of treatment, and according the Radiation Therapy Oncology Group's Toxicity Criteria (RTOGTC) during Chemoradiotherapy.; Toxicity profile.
    Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.0), during the preoperative and postoperative phases of treatment, and according the Radiation Therapy Oncology Group's Toxicity Criteria (RTOGTC) during chemoradiotherapy.
    Tasso di resezioni R0.
    Il tasso di resezione R0 è definito come la percentuale di pazienti, rispetto al totale dei soggetti arruolati, sottoposti a resezione R0 del tumore primario. La chirurgia R0 è definita come rimozione chirurgica completa della malattia senza margini microscopici.; Downstaging tumorale.
    La riduzione del tumore è definita come la riduzione di almeno un livello nella stadiazione T o N tra la RMN al basale e la stadiazione istopatologica, senza evidenza di progressione o progressione della
    malattia.; Recidiva locale.
    La recidiva locale è definita come una recidiva intrapelvica dopo resezione del cancro del retto primario, con o senza metastasi distali.; Tasso di preservazione dello sfintere.
    Il tasso di preservazione dello sfintere è definito come la percentuale di pazienti sottoposti a chirurgia con questo scopo.; Sopravvivenza libera da progressione (PFS).
    La PFS è definita come il tempo tra l'inizio del trattamento e uno dei seguenti eventi: chirurgia non radicale del tumore primario (resezione R2), recidiva locoregionale dopo resezione R0 / 1 del tumore primitivo, malattia metastatica o progressione o morte per qualsiasi causa.
    La determinazione della progressione della malattia si baserà su misurazioni riportate dallo sperimentatore. I pazienti che sono vivi senza avere uno degli eventi sopra riportati alla fine dello studio saranno censorizzati alla loro ultima valutazione radiologica.; Sopravvivenza globale (OS).
    La sopravvivenza globale (OS) è definita come il tempo che intercorre tra l'inizio del trattamento e la data di morte per qualsiasi causa. Per i pazienti ancora in vita al momento dell'analisi, l'OS sarà censorizzata all'ultima data in cui i pazienti erano noti essere vivi.; Profilo di sicurezza.
    Il tasso di tossicità complessivo è definito come la percentuale di pazienti, rispetto al totale dei soggetti arruolati, che sperimentano qualsiasi evento avverso, in base ai National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) versione 4.0, durante le fasi preoperatorie e postoperatorie del trattamento e secondo i Radiation Therapy Oncology
    Group's Toxicity Criteria (RTOGTC) durante la chemioradioterapia.; Profilo di tossicità.
    Il tasso di tossicità è definito come la percentuale di pazienti, rispetto al totale dei soggetti arruolati, che presentano uno specifico evento avverso di grado 3/4, secondo i National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE versione 4.0), durante le fasi preoperatorie e postoperatorie del trattamento e secondo i Radiation Therapy Oncology Group's Toxicity Criteria (RTOGTC) durante la chemioradioterapia.
    E.5.2.1Timepoint(s) of evaluation of this end point
    28 months; 48 months; 48 months; 48 months; 48 months; 48 months; 48 months; 48 months
    28 mesi; 48 mesi; 48 mesi; 48 mesi; 48 mesi; 48 mesi; 48 mesi; 48 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 Yes
    E.8.1.1Randomised No
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    nessun comparatore
    no comparator
    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 concerned15
    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
    May 2020
    Maggio 2020
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months48
    E.8.9.1In the Member State concerned days14
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months48
    E.8.9.2In all countries concerned by the trial days14
    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: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 61
    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 state101
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 101
    F.4.2.2In the whole clinical trial 101
    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 every three months for two years, then every 6 months until the fifth years
    Follow-up ogni tre mesi per i primi 2 anni, poi ogni 6 mesi fino a 5 anni
    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 Decision2019-01-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-01-17
    P. End of Trial
    P.End of Trial StatusOngoing
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