Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43931   clinical trials with a EudraCT protocol, of which   7307   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2021-003659-40
    Sponsor's Protocol Code Number:CNS-201
    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:2022-09-14
    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 number2021-003659-40
    A.3Full title of the trial
    A Multicenter, Open-Label Study with a Randomized Control Arm of the Efficacy, Safety, and Pharmacokinetics of Intravenously Infused Berubicin in Adult Patients with Recurrent Glioblastoma Multiforme (WHO Grade IV) After Failure of Standard First Line Therapy
    Studio multicentrico in aperto con un braccio di controllo randomizzato volto a valutare l'efficacia, la sicurezza e la farmacocinetica di berubicina infusa per via endovenosa in pazienti adulti affetti da glioblastoma multiforme ricorrente (Grado IV secondo l’OMS) dopo il fallimento della terapia standard di prima linea
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of Berubicin in Adult Patients with Recurrent Glioblastoma Multiforme
    Studio di berubicina in pazienti adulti con glioblastoma multiforme ricorrente
    A.3.2Name or abbreviated title of the trial where available
    NA
    NA
    A.4.1Sponsor's protocol code numberCNS-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04762069
    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 SponsorCNS Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCNS Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCNS Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointZena Muzyczenko
    B.5.3 Address:
    B.5.3.1Street Address2100 West Loop South, Suite 900
    B.5.3.2Town/ cityHouston
    B.5.3.3Post codeTX 77027
    B.5.3.4CountryUnited States
    B.5.4Telephone number+7325888260
    B.5.6E-mailzmuzy@cnspharma.com
    D. IMP Identification
    D.IMP: 1
    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.2.1.1.1Trade name Cecenu®
    D.2.1.1.2Name of the Marketing Authorisation holdermedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 name-
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCCNU
    D.3.9.2Current sponsor codeLomustine
    D.3.9.3Other descriptive nameLOMUSTINE
    D.3.9.4EV Substance CodeSUB08567MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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: 2
    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.2.5The 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 nameGLUCOSIO 5%
    D.3.2Product code [-]
    D.3.4Pharmaceutical form 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 codeNA
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 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 nameBerubicin
    D.3.2Product code [WP 744]
    D.3.4Pharmaceutical form Lyophilisate 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 INNBerubicin
    D.3.9.1CAS number 293736-67-1
    D.3.9.2Current sponsor codeWP 744
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number18
    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.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
    Glioblastoma Multiforme (WHO Grade IV)
    glioblastoma multiforme (Grado IV secondo l’OMS)
    E.1.1.1Medical condition in easily understood language
    Glioblastoma multiforme (GBM)
    glioblastoma multiforme (GBM)
    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
    To assess the effect of berubicin compared with lomustine on OS in adult patients with GBM that has recurred or progressed after standard initial therapy.
    Valutare l'effetto della berubicina rispetto alla lomustina OS in pazienti adulti affetti da GBM ricorrente o progressivo dopo terapia iniziale standard
    E.2.2Secondary objectives of the trial
    To assess the effect of berubicin on PFS per RANO criteria in patients with GBM after failure of standard first line therapy, defined as the length of time from the initiation of study drug administration to disease progression based on MRI scan.
    To assess the effect of berubicin on EFS defined as the length of time from the initiation of study drug administration to disease progression, death, or discontinuation of treatment for any reason.
    To assess the effect of berubicin on ORR defined as complete and partial responses (CR+PR respectively) as well as DCR defined as CR+PR+SD per RANO criteria in adult patients with GBM after failure of standard first line therapy.
    To assess the safety of the RP2D of berubicin given as a 2-hour IV infusion once daily for 3 consecutive days followed by 18 days off study drug (each cycle = 21 days) by the incidence and severity of AEs according to NCI-CTCAE, Version 5.0.
    To confirm the pharmacokinetics (PK) of berubicin and itsmetabolite, berubicinol.
    Valutare l'effetto della berubicina:
    - sulla sopravvivenza libera da progressione (PFS) secondo i criteri RANO in pazienti affetti da GBM dopo il fallimento della terapia standard di prima linea, definita come il tempo intercorso tra l'inizio della somministrazione del farmaco in studio e la progressione della malattia sulla base della RMI.
    - sulla sopravvivenza libera da eventi (EFS) definita come tempo intercorso tra l'inizio della somministrazione del farmaco in studio e progressione della malattia, decesso o interruzione del trattamento per qualsiasi motivo.
    - sui tassi di risposta obiettiva (ORR) definiti come risposte complete e parziali (rispettivamente CR + PR) così come sui tassi di controllo della malattia (DCR) definiti come CR + PR + SD secondo i criteri RANO in pazienti adulti affetti da GBM dopo il fallimento della terapia standard di prima linea.

    Per i rimenenti obiettivi secondari fare riferimento al protocollo di studio e alla sinossi
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Written informed consent from the patient or their legally authorized representative (LAR) prior to any study-related procedure, and willing and able to comply with the protocol and aware of the investigational nature of this study.
    2.At least 18 years of age.
    3.KPS score =60.
    4. A confirmed GBM diagnosis must be based on local review of tumor tissue from the initial biopsy, surgery, or re-resection. A formal pathology report confirming GBM is acceptable. It is not a requirement for slides to be sent to a central reviewer.
    5.Recurrent or progressive GBM as evaluated by central review applying RANO criteria on contrast MRI scans of the Baseline/Screening MRI scan obtained up to six weeks prior to C1D1 and a historical scan taken before the Baseline/Screening scan.
    please refer to inclusion criteria 5 in the protocol for additional details.
    6.The tumor is localized supratentorially with no leptomeningeal (local or distant), spinal or CSF metastases, and no ventricular invasion (explicit documentation of the disease progression that would be problematic in evaluating the efficacy of this drug).
    7.MGMT methylation status must be available; results of routinely used methods for MGMT methylation testing (eg, methylation-specific polymerase chain reaction or quantitative polymerase chain reaction) are acceptable.
    8.No more than 1 prior line of treatment (eg, surgery followed by radiation with concomitant chemotherapy, followed by adjuvant chemotherapy is considered as 1 line of treatment). In addition, treatment with tumor treating fields (TTFields; Optune¿) is acceptable if provided as first line therapy prior to progression or recurrence of disease.
    9.A second debulking surgery, additional radiation or gamma knife surgery during the first line of treatment or after progression, and for which the investigator does not suspect pseudoprogression is acceptable, as long as no chemotherapy or immunotherapy has been provided.

    for remaining inclusion criteria please refer to the study protocol
    Consenso informato scritto da parte del paziente o relativo rappresentante legalmente autorizzato (LAR) prima di qualsiasi procedura correlata allo studio, volontà e capacità di rispettare il protocollo e consapevolezza della natura sperimentale di questo studio.
    2. Età pari ad almeno 18 anni.
    3. Punteggio KPS =60
    4. Diagnosi confermata di GBM che deve essere basata sulla revisione a livello locale del tessuto tumorale proveniente da biopsia iniziale, chirurgia o nuova resezione. È accettabile un referto di anatomia patologica formale che confermi il GBM. L'invio di vetrini a un revisore centrale non è un requisito.
    5. GBM ricorrente o progressivo in base alla valutazione della revisione centrale che applica i criteri RANO su scansioni RMI rispetto alle scansioni RMI al basale/screening ottenute fino a sei settimane prima del C1G1 e una scansione storica eseguita prima della scansione basale/di screening che soddisfa almeno 1 dei seguenti criteri:
    Nel caso di malattia misurabile, la progressione sarà documentata da = 25% di aumento nella somma dei prodotti dei diametri perpendicolari (SPDP) delle lesioni misurabili evidenziate dal mezzo di contrasto o qualsiasi nuova lesione (target) misurabile.
    b. Se le SPDP non possono essere stimate in modo affidabile a causa della complessa cospicuità della lesione, della forma e del modello di evidenza del mezzo di contrasto, si può usare invece il volume di tutte le lesioni misurabili e non misurabili, applicando la stessa soglia (aumento = 25%) per confermare la progressione della malattia.
    c. Nel caso di lesioni non misurabili nella scansione storica, qualsiasi trasformazione in lesioni misurabili (=10 mm in entrambi i diametri massimi perpendicolari) nella scansione al basale/screening costituirà evidenza di progressione.
    d. Se ci sono solo lesioni non misurabili (non target) nella scansione al basale/screening, lesioni/sedi aggiuntive saranno considerate evidenza di progressione in base alla scansione storica. I pazienti con nuove infiltrazioni di liquido cerebrospinale (CSF) non saranno considerati eleggibili.
    e. Se le scansioni storiche non sono disponibili, il revisore centrale può utilizzare un referto radiologico di una scansione fatta prima della scansione al basale/screening che documenta gli SPDP da una scansione precedente della malattia in aumento o del suo volume per valutare l’eleggibilità se dimostra gli standard di qualità e le linee guida di acquisizione richieste.
    f. Se la scansione ottenuta durante lo standard di cura (prima dell'inizio dello screening clinico formale e dell'arruolamento dei pazienti) viene usata come scansione basale/di screening e non è completamente conforme agli standard di qualità e alle linee guida di acquisizione per la lettura centrale (cioè, artefatti o sequenze mancanti), questa può essere usata ai fini dell'inclusione se il lettore centrale, discutendo con lo sponsor e il PI, concorda che fornisce evidenze basate su pratiche cliniche standard di recidiva o progressione.
    g. I pazienti alla prima progressione che vengono trattati con ri-resezione o biopsia per confermare la progressione non devono presentare malattia misurabile alla loro scansione di screening post-operatoria come scansione basale/di screening. Questi pazienti devono essere stabili dal punto di vista medico dopo la procedura, come valutato dal PI, e presentare la scansione basale/di screening entro 7 giorni prima di iniziare il trattamento.
    Il tumore è localizzato a livello sopratentoriale senza metastasi leptomeningee (locali o distanti), spinali o del CSF, e senza invasione ventricolare (documentazione esplicita della progressione della malattia che sarebbe problematica nella valutazione dell'efficacia di questo farmaco).
    7. Lo stato di metilazione MGMT deve essere disponibile; sono accettabili i risultati di metodi usati di routine per il test di metilazione della MGMT (ad es. reazione a catena della polimerasi specifica per la metilazione o reazione a catena della polimerasi quantitativa).
    8. Non più di 1 linea di trattamento precedente (ad es. la chirurgia seguita da radioterapia con chemioterapia concomitante, seguita da chemioterapia adiuvante è considerata come 1 linea di trattamento). Inoltre, è accettabile l'impiego di campi elettrici per il trattamento del tumore (TTField; Optune ®) se usati come terapia di prima linea prima della progressione o ricorrenza della malattia.
    9. È accettabile un secondo debulking chirurgico, un'ulteriore radiazione o un intervento con gamma knife durante la prima linea di trattamento o dopo la progressione, e per il quale lo sperimentatore non sospetti una pseudoprogressione, a condizione che non sia stata fornita alcuna chemioterapia o immunoterapia

    per i rimanenti criteri di inclusione fare riferimento al protocollo di studio
    E.4Principal exclusion criteria
    1.Unable or not willing to comply with the protocol regulations.
    2.Any additional chemotherapy (including but not limited to temozolomideor immunotherapy)for recurrent or progressive GBM after a first line treatment.
    3.Prior treatment with bevacizumab.
    4.Prior treatment with lomustine.
    5.Known to have an IDH mutation prior to enrollment
    6.Screening/Baseline MRI showing a mass effect defined as significant compression of the ventricular system and/or midline shift with associated clinical symptoms deemed inappropriate for the patient to enter a clinical trial. If there is otherwise asymptomatic compression and/or midline shift and the patient fulfills all other criteria, these patients are considered eligible.
    7.Any condition (medical, social, psychological) that would prevent adequate information and follow-up, including but not limited to clinically relevant psychiatric disorders, legal incapacity, dementia, adults protected by law or altered mental status.
    8.Presence of poorly controlled seizures, defined as occurring despite standard of care (SOC) or requiring hospitalization.
    9.Prior anthracycline cumulative dose more than 550 mg/m2. Further information is presented in Appendix 2.
    10.Heart disease: a.Left ventricular ejection fraction (LVEF) <50%b.Unstable anginac. Congestive heart failure with New York Heart Association classification of 3 or4 d.Patients with baseline QT/QTc interval >480 msec, a history of
    additional risk factors for torsades de pointes (eg, heart failure, hypokalemia, family history of long QT syndrome) and using concomitant medications that significantly prolong the QT/QTc intervale. History of myocardial infarction within 12 months of enrollmentf. Severe arrhythmia not controlled by medication
    11.Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg and/or diastolic BP >100 mmHg)sustained over 2measurements.
    12.Known to be positive for hepatitis B virus surface antigen, hepatitis C virus, human immunodeficiency virus, coronavirus disease-2019 (COVID-19 [currently positive at time of screening]) or any other acute viral, bacterial, or fungal infection (testing not required unless symptomatic or suspected
    disease).
    13.Patients with any other uncontrolled intercurrent medical conditions, including but not limited to diabetes mellitus or chronic obstructive pulmonary disease that have not been well controlled by medical management over the prior 3 months are ineligible unless approved by the sponsor.
    14.Women who are lactating or breastfeeding
    1. Incapacità o non volontà di rispettare le disposizioni del protocollo.
    2. Qualsiasi chemioterapia (inclusa a titolo di esempio la temozolomide o immunoterapia) per GBM ricorrente o progressivo dopo un trattamento di prima linea.
    3. Precedente trattamento con bevacizumab.
    4. Precedente trattamento con lomustina.
    5. Nota presenza di una mutazione IDH prima dell'arruolamento
    6. RMI di screening/basale che mostra un effetto massa definito come una compressione significativa del sistema ventricolare e/o spostamento della linea mediana con sintomi clinici associati ritenuti inappropriati per l’ammissione del paziente in uno studio clinico. Se si verifica compressione e/o spostamento della linea mediana altrimenti asintomatico e il paziente soddisfa tutti gli altri criteri, questi pazienti sono considerati eleggibili.
    7. Qualsiasi condizione (medica, sociale, psicologica) che impedirebbe di garantire informazioni e follow-up adeguati, inclusi a titolo di esempio disturbi psichiatrici clinicamente rilevanti, incapacità legale, demenza o stato mentale alterato.
    8. Presenza di crisi convulsive scarsamente controllate, definite come insorgenti nonostante lo standard di cura (SOC) o che richiedono l'ospedalizzazione.
    9. Precedente dose cumulativa di antraciclina superiore a 550 mg/m2. Ulteriori informazioni sono presentate nell'Appendice 2.
    10. Malattia cardiaca:
    a. Frazione di eiezione ventricolare sinistra (LVEF) < 50%
    b. Angina instabile
    c. Insufficienza cardiaca congestizia di classe 3 o 4 secondo la New York Heart Association
    d. Pazienti con intervallo QT/QTc basale > 480 msec, anamnesi di ulteriori fattori di rischio per torsione di punta (ad es. insufficienza cardiaca, ipopotassiemia, anamnesi familiare di sindrome del QT lungo) e uso di farmaci concomitanti che prolungano significativamente l'intervallo QT/QTc
    e. Anamnesi di infarto miocardico nei 12 mesi precedenti l'arruolamento
    f. Aritmia grave non controllata da farmaci
    11. Ipertensione non controllata (pressione arteriosa [BP] sistolica > 150 mmHg e/o BP diastolica > 100 mmHg) sostenuta nel corso di 2 misurazioni.
    12. Nota positività all'antigene di superficie del virus dell'epatite B, al virus dell'epatite C, al virus dell'immunodeficienza umana, alla malattia da coronavirus 2019 (COVID-19 [positività al momento dello screening]) o a qualsiasi altra infezione virale, batterica o fungina acuta (non è richiesto il test salvo in caso di soggetto sintomatico o sospetto di malattia).
    13. I pazienti con qualsiasi altra condizione medica intercorrente non controllata, compresi a titolo di esempio diabete mellito o malattia polmonare ostruttiva cronica, che non sono stati ben controllati dalla gestione medica nell'arco dei 3 mesi precedenti non sono eleggibili, salvo dietro approvazione dello Sponsor.
    14. Donne che stiano allattando o che siano in fase di allattamento
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is OS.
    L'endpoint primario dello studio è l'OS
    E.5.1.1Timepoint(s) of evaluation of this end point
    through study completion, an average of 4 years
    fino al completamento dello studio, una media di 4 anni
    E.5.2Secondary end point(s)
    PFS, defined as the length of time from the initiation of study drug administration to disease progression based on MRI scan
    EFS, defined as the length of time from the initiation of study drug administration to disease progression, death, or discontinuation of treatment for any reason (eg, toxicity, intolerance, disease-related conditions, or failure to respond)
    ORR, defined as CR + PR per RANO criteria
    •DCR, defined as CR + PR + SD per RANO criteria; SD is defined as lack of progression of disease based on MRI scan obtained at least 6 weeks after initiation of therapy
    The PK endpoint of this study is:
    • Standard PK parameters for berubicin and its metabolite, berubicinol, as derived from noncompartmental analysis of plasma drug concentration-time data.
    PFS, definita come il tempo intercorso tra l'inizio della somministrazione del farmaco in studio e la progressione della malattia sulla base della RMI
    EFS, definita come il tempo intercorso tra l'inizio della somministrazione del farmaco in studio e la progressione della malattia, il decesso o l'interruzione del trattamento per qualsiasi motivo (ad es. tossicità, intolleranza, condizioni correlate alla malattia o mancata risposta)
    ORR, definito come CR + PR secondo i criteri RANO
    DCR, definito come CR + PR + SD secondo i criteri RANO; la SD è definita come assenza di progressione della malattia sulla base della RMI ottenuta almeno 6 settimane dopo l'inizio della terapia
    L'endpoint di farmacocinetica dello studio è:
    Parametri PK standard per la berubicina e il relativo metabolita, berubicinol, derivati dall'analisi non compartimentale dei dati di concentrazione di farmaco nel plasma-tempo.
    E.5.2.1Timepoint(s) of evaluation of this end point
    through study completion, an average of 4 years
    fino al completamento dello studio, una media di 4 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 Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic 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 Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    France
    Spain
    Switzerland
    Italy
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    Ultima visita ultimo paziente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    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: 42
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 168
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 84
    F.4.2.2In the whole clinical trial 210
    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)
    treatment or care after the subject has ended the participation in the trial will not be different from the expected normal treatment of the studied condition
    il trattamento o cura dopo che il soggetto ha terminato la partecipazione allo studio non sarà differente dal normale trattamento atteso per la condizione in studio
    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 Decision2022-11-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-11-14
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA