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    Summary
    EudraCT Number:2021-003774-32
    Sponsor's Protocol Code Number:N/A
    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:2021-09-02
    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 number2021-003774-32
    A.3Full title of the trial
    Enhancing Treatment in Persistent Glioblastoma through AGuIX Nanoparticles for Precision Radiotherapy (NanoGBM-Precision): A Phase II, monocenter, open-label, single-arm, no-profit clinical trial.
    Potenziamento della radioterapia di precisione nel trattamento del glioblastoma persistente tramite l’utilizzo di nanoparticelle AGuIX (NanoGBM-Precision): uno studio clinico di Fase II, monocentrico, in aperto, a singolo braccio di trattamento, no-profit
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to evaluate the potentiation effect of radiotherapy by AGuIX nanoparticles for the treatment of persistent glioblastoma
    Studio per valutare l'effetto di potenziamento della radioterapia da parte di nanoparticelle AGuIX per la cura del glioblastoma persistente
    A.3.2Name or abbreviated title of the trial where available
    NanoGBM-Precision
    NanoGBM-Precision
    A.4.1Sponsor's protocol code numberN/A
    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 SponsorDIPARTIMENTO BIOMEDICINA E PREVENZIONE UNIVERSITà DEGLI STUDI DI ROMA TOR VERGATA
    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 supportAIRC
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationLink Neuroscience and Health Care srl - L.N.Age srl
    B.5.2Functional name of contact pointClinical Operation
    B.5.3 Address:
    B.5.3.1Street AddressVia Mario Savini 15
    B.5.3.2Town/ cityRoma
    B.5.3.3Post code00136
    B.5.3.4CountryItaly
    B.5.6E-mailergena.melengu@lnage.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 nameAGuIX
    D.3.2Product code [N/A]
    D.3.4Pharmaceutical form Powder for 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 coden/a
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    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 Yes
    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.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
    Persistent Glioblastoma Multiforme, grade IV
    Glioblastoma Multiforme Persistente, grado IV
    E.1.1.1Medical condition in easily understood language
    Persistent Glioblastoma Multiforme, grade IV
    Glioblastoma Multiforme Persistente, grado IV
    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 10018337
    E.1.2Term Glioblastoma multiforme
    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
    We will translate the C-map, T1-map based, MRI technique pioneered by the applicant and optimize it for human scanners and human clearance rates. This will allow to derive individual tumor concentration maps as well as AGuIX clearance curves (see preliminary results), hence deriving a precise and personalized spatiotemporal characterization of AGuIX pharmacodynamics and therefore maximum boost in RT efficacy.
    L’obiettivo primario è la creazione di un protocollo AGuIX-RT personalizzato: usando la metodologia C-maps, ottenuta dalla T1-map, acquisita tramite RM prima e dopo somministrazione di AGuIX. Ciò consentirà di ricavare mappe di concentrazione tumorale individuali e curve di clearance di AGuIX, derivando quindi una caratterizzazione spaziotemporale precisa e personalizzata della farmacodinamica di AGuIX e quindi il massimo aumento dell'efficacia della RT.
    E.2.2Secondary objectives of the trial
    We will evaluate the effect of AGuIX-enhanced RT (see O1) on GBM evolution in 30 patients. Moreover, patients who fail the screening will be treated with standard treatment and observed. All patients will undergo longitudinal multimodal neuroimaging to evaluate tumor metabolism and GTV. Quality of life (QOL) will be evaluated before and during two years since protocol inception through the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Cognitive abilities will be measured by the Mini-Mental State Exam (MMSE) and Montreal Cognitive Assessment (MoCA) test. Finally, the following parameters will be collected and recorded by the physician in order to assess common side effects arising during RT+TMZ: nausea, vomiting, anorexia, rash, increased liver enzymes, hypoalbuminemia, pneumonia, deep vein thrombosis, pulmonary thromboembolism, infections, thrombocytopenia, lymphopenia, neutropenia, anemia, death from the pathology under study.
    •Metabolismo e volume della massa tumorale
    •Qualità della vita
    •Stato neuropsicologico e cognitivo
    •Effetti collaterali legati alla chemioradioterapia: nausea, vomito, anoressia, eruzione cutanea, aumento degli enzimi epatici, ipoalbuminemia, polmonite, trombosi venosa profonda, tromboembolia polmonare, infezioni, trombocitopenia, linfopenia, neutropenia, anemia, morte per la patologia in esame.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients who have previously a partial resection, biopsy or radiological diagnosis of Glioblastoma multiforme (GBM, WHO grade IV).
    2. Not fit for Standard RT (60Gy/30 fractions over 6 weeks) in combination with Temozolomide
    3. Patient’s age > 18 yo
    4. Life expectancy = 3 months
    5. Liver function (GGT, PAL, ASAT, ALAT, bilirubin) <1.5 times the upper normal limit
    6. For patients receiving treatment with corticosteroids, treatment with corticosteroids must be at a stable or decreasing dose for at least 14 days before inclusion
    7. Patient able to swallow and retain oral medication
    8. Patients who have not received prior CHT or RT
    9. Adequate renal function with standardized creatinine clearance = 50ml/min/1.73m²
    10. Adequate hematological and hepatic functions: Platelet count > 100x10(9)/L (100,000 cells/mm3), Absolute granulocyte count (AGC) > 1.5 x 10(9)/L (1.500 cells/mm3), total serum bilirubin < 1.5 times the upper limit of normal, ALT (GPT) < 2.5 times the upper limit of normal and/or AST <2.5 times upper limit of normal.
    11. Patient is able and willing to complete the quality-of-life questionnaires in Italian or any other official language into which the questionnaire is required to be translated. The baseline assessment must have already been completed.
    12. Negative serum pregnancy test within 7 days before the first administration of treatment for women.
    13. Women of childbearing potential and men whose partners are of childbearing potential must agree to use, themselves or their partners, an approved method of contraception throughout the treatment and at least 6 months after the last administration of study treatment.
    14. Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements.
    1. Pazienti che hanno avuto precedentemente una resezione parziale, biopsia o diagnosi radiologica di Glioblastoma multiforme (GBM, WHO grado IV)
    2. Non adatti per la RT standard (frazioni 60Gy/30 frazioni oltre 6 settimane) in combinazione con Temozolomide
    3. Età del paziente > 18 anni
    4. Aspettativa di vita = 3 mesi
    5. Funzionalità epatica (GGT, ALP, AST, ALT, bilirubina) <1,5 volte il limite normale superiore
    6. Per i pazienti che ricevono un trattamento con corticosteroidi, il trattamento con corticosteroidi deve essere a una dose stabile o decrescente per almeno 14 giorni prima dell'inclusione nello studio
    7. Paziente in grado di deglutire e trattenere i farmaci orali
    8. Pazienti che non hanno ricevuto chemioterapia o RT precedenti
    9. Adeguata funzione renale con clearance standardizzata della creatinina = 50ml/min/1,73m²
    10. Adeguate funzionalità ematologiche ed epatiche: conteggio delle piastrine>100x10(9)/L (100.000 cellule/mm3), conteggio assoluto dei granulociti (AGC)>1,5 x 10(9)/L (1.500 cellule/mm3), bilirubina sierica totale < 1,5 volte il limite superiore normale, ALT (GPT) < 2,5 volte il limite superiore normale e/o AST <2,5 volte il limite superiore normale.
    11. Il paziente deve essere in grado e disposto a compilare i questionari sulla qualità della vita in italiano o in qualsiasi altra lingua ufficiale in cui il questionario deve essere tradotto. La valutazione basale deve essere già stata completata.
    12. Test di gravidanza su siero negativo entro 7 giorni antecedenti la prima somministrazione del trattamento per le donne in età fertile.
    13. Le donne in età fertile e gli uomini le cui partner sono in età fertile devono accettare di utilizzare, per se stessi o per i loro partner, un metodo di contraccezione approvato durante tutto il trattamento e almeno 6 mesi dopo l'ultima somministrazione del trattamento oggetto di studio.
    14. Il consenso del paziente deve essere ottenuto in base ai requisiti locali in accordo con alla regolamentazione del Comitato di Sperimentazione Umana locale Istituzionale e/o Universitaria.
    E.4Principal exclusion criteria
    1. Patients unable to undergo or tolerate MRI
    2. Patients with contra-indication, sensitivity, or allergy to gadolinium or gadolinium-based contrast agents
    3. Patients who have previously received brain irradiation
    4. Patients with negative MRI within 72 hours after surgery
    5. Age <18 yo
    6. Standardized creatinine clearance < 50ml/min/1.73m²
    7. History of nephropathy
    8. Patients with, serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment or with any condition that does not permit compliance with the protocol
    9. Patients with known hypersensitivity to temozolomide or compounds with similar chemical composition to temozolomide.
    10. Patients with known contra-indication, sensitivity or allergy to gadolinium
    11. Patients unable to undergo or tolerate Magnetic Resonance Imaging or with known contra-indication (e.g. cardiac pacemaker, implanted defibrillator, certain cardiac valve replacements or certain metal implants).
    12. Pregnancy or breastfeeding
    13. Subject under administrative or judicial control
    14. Psychological disorder or social or geographic reasons that may compromise medical monitoring of the trial or compliance with treatment
    1. Pazienti incapaci di sottoporsi o tollerare la risonanza magnetica
    2. Pazienti con controindicazioni, sensibilità o allergia agli agenti di contrasto a base di gadolinio o gadolinio-derivati
    3. Pazienti che hanno precedentemente ricevuto irradiazione cerebrale
    4. Pazienti con risonanza negativa entro 72 ore dall'intervento chirurgico
    5. Età <18 anni
    6. Clearance standardizzata della creatinina < 50ml/min/1.73m²
    7. Storia di nefropatia
    8. Pazienti con gravi condizioni mediche sottostanti che comprometterebbero la capacità del paziente di ricevere i trattamenti previsti dal protocollo con qualsiasi condizione che non consenta il rispetto del protocollo
    9. Pazienti con ipersensibilità nota alla temozolomide o ai composti con composizione chimica simile alla temozolomide.
    10. Pazienti con note controindicazioni, sensibilità o allergia noti al gadolinio
    11. Pazienti incapaci di sottoporsi o tollerare la risonanza magnetica o con nota controindicazione (ad esempio pacemaker cardiaco, defibrillatore impiantato, alcune sostituzioni della valvola cardiaca o alcuni impianti metallici)
    12. Gravidanza o allattamento
    13. Soggetto sotto controllo amministrativo o giudiziario
    14. Disturbo psicologico o motivi sociali o geografici che possono compromettere il monitoraggio medico dello studio o il rispetto del trattamento
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will be overall response rate (ORR), defined as the percentage of patients who have a partial or complete response to therapy according to RANO criteria
    Percentuale di pazienti che hanno una risposta parziale o completa alla terapia secondo i criteri RANO.
    E.5.1.1Timepoint(s) of evaluation of this end point
    End of trial
    Fine dello studio
    E.5.2Secondary end point(s)
    1.PFS, defined as the time interval between the date of randomization and the date of disease progression or death. Disease progression is defined as objective radiological progression or neurological, clinical progression.
    2.OS, defined as the time interval between the date of randomization and the date of death from any cause. Toxicity defined as ability of a chemical substance or pharmaceutical preparation to cause, at certain doses or concentrations, disturbances, or damage to living organisms to which they have been administered.
    3.QoL, as Measured by FACT-Br, cognition after treatment as Measured by the MMSE and MoCA test. All patients must complete a quality-of-life questionnaire before, during and after the follow-up.
    4.Side effects, filling in a questionnaire with the following parameters: nausea, vomiting, anorexia, rash, increased liver enzymes, hypoalbuminemia, pneumonia, deep vein thrombosis, pulmonary thromboembolism, infections, thrombocytopenia, lymphopenia, neutropenia, anemia, death from the pathology under study.
    1.lntervallo di tempo tra la data di randomizzazione e la data di progressione della malattia o morte per la patologia oggetto di studio. La progressione della malattia è definita come progressione radiologica oggettiva o progressione neurologica e clinica
    2.Intervallo di tempo tra la data di randomizzazione e la data di morte per qualsiasi causa. La tossicità viene definita come capacità di una sostanza chimica o di un preparato farmaceutico di causare, a determinate dosi o concentrazioni, disturbi o danni agli organismi viventi ai quali sono stati somministrati.
    3.Test Fact-BR, MMSE, MoCA
    4.Compilazione di un questionario per la registrazione degli effetti collaterali legati alla chemioradioterapia: nausea, vomito, anoressia, eruzione cutanea, aumento degli enzimi epatici, ipoalbuminemia, polmonite, trombosi venosa profonda, tromboembolia polmonare, infezioni, trombocitopenia, linfopenia, neutropenia, anemia, morte per la patologia in esame.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1.When the event occurs
    2.When the event occurs
    3.Ad each visit
    4.Ad every visit
    1.Quando si manifesta l'evento
    2.Quando si manifesta l'evento
    3.Ad ogni visita
    4.Ad ogni visita
    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 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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    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
    The end of the trail is defined as last patient last visit i.e. either the date of the last visit of the last patient to complete the study or the date at which the last data point from the last patient, which is required for endpoints analysis, is received whichever is the later date.
    La fine dello studio è definita come l'ultima visita del'ultimo paziente, cioè la data dell'ultima visita dell'ultimo paziente per completare lo studio o la data in cui viene ricevuto l'ultimo dato dell'ultimo paziente, necessario per l'analisi degli endpoint, a seconda della data successiva.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 30
    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)
    According to the discretion of the attending physician
    Secondo discrezione del medico curante
    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 Decision2021-12-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-01-26
    P. End of Trial
    P.End of Trial StatusOngoing
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