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   43925   clinical trials with a EudraCT protocol, of which   7306   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:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-09-10
    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 ConcernedSpain - AEMPS
    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
    Estudio multicéntrico, sin enmascaramiento con un grupo de referencia aleatorizado para evaluar la eficacia, la seguridad y la farmacocinética de berubicina mediante infusión intravenosa en pacientes adultos con glioblastoma multiforme (grado IV de la OMS) recidivante tras el fracaso del tratamiento de referencia de primera línea 
    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
    Un estudio de Berubicina en Pacientes Adultos con Gliobastoma Recidivante Multiforme
    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 number732-588-8260
    B.5.5Fax numberN/A
    B.5.6E-mailzmuzy@cnspharma.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 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 number18.9
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 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.3.4Pharmaceutical 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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 de la 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 (WHO Grade IV) that has recurred after standard initial therapy.
    Evaluar el efecto de la berubicina en comparación con la lomustina sobre la supervivencia global (SG) en pacientes adultos con GBM (grado IV de la OMS) recidivante tras un tratamiento estándar inicial
    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 and individual components (ie, CR alone, PR alone) as well as DCR defined as CR or PR or 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 of berubicin and its metabolite, berubicinol.
    Evaluar el efecto de la berubicina en SLP según criterios RANO en pacientes con GBM tras fallo con tratamiento de primera línea(T1L), definido como T transcurrido desde el inicio de admin del fármaco en estudio(AFE) hasta la progresión de la enfermedad(PE) detectada con RMN/Evaluar el efecto de la berubicina en SLEv, definida como el T desde el inicio de AFE hasta la PE, la muerte o la interrupción del tratamiento por cualquier razon/Evaluar efecto de berubicina en TRO y los componentes individuales (ej RC sola o RP sola) y con las tasas de control de la enfermedad(TCE), definidas como una RC o RP, según RANO en pacientes adultos con GBM tras el fallo T1L./Evaluar la seguridad de la DF2R de berubicina en infusión intravenosa de 2h, 1vez al día en 3días consecutivos, tras 18 días sin tratamiento de estudio (ciclos=21día) en función de la incidencia y gravedad de AA según NCI-CTCAE v5.0./Confirmar la farmacocinética de la berubicina y su metabolito,berubicinol.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent [...]
    2. At least 18 years of age.
    3. 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.
    4. Recurrent GBM as evaluated by RANO criteria, confirmed by central review, as follows: Measurable disease is required with documented unequivocal evidence of tumor recurrence or progression following prior therapy (ie, 25% increase in the sum of the products of perpendicular diameters of the contrast-enhancing lesions while on stable or increasing doses of corticosteroids; however, these changes should not be due to changes in the dose of corticosteroids) as documented by the investigator.
    5. The tumor is localized supratentorially.
    6. The lesion (or sum of lesions) does not exceed 50 cm3 in volume.
    7. MGMT methylation status must be available; results of routinely used methods for MGMT methylation testing (eg, methylation-specific PCR or quantitative PCR) 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). A second debulking surgery during the first line treatment is acceptable. In addition, treatment with tumor treating fields (TTFields; Optune) is acceptable if provided as first line therapy.
    9. Recovery from toxicity/side effects of all prior therapy to Grade 1 or less, subject to the investigator’s discretion, except for alopecia; the following time intervals from previous treatments are required to be eligible:
    a. 12 weeks from the completion of radiation (to reduce risk of pseudoprogression), unless progression is confirmed by biopsy
    b. 4 weeks from the end of any previous of chemotherapy or 6 weeks after the end of treatment with nitrosoureas
    c. 4 weeks from the end of any TTFields treatment
    d. 4 weeks from any major surgery (maximal debulking surgery, either gross total resection or partial resection) or significant traumatic injury, and any surgery incisions or wounds must be completely healed
    10. A stable or decreasing dose of corticosteroids (or none) for brain edema for at least 5 days prior to baseline MRI and enrollment in the study to document disease progression such that changes in the MRI are not related to the use of corticosteroids.
    11. Immunosuppressive therapies allowed include the use of topical, inhalational, ophthalmic or intra-articular glucocorticoids, or the use of physiologic replacement doses of glucocorticoids.
    12. Eligible for chemotherapy based on adequate bone marrow function and organ function within 2 weeks of study treatment as defined by the following and subject to the investigator’s discretion:
    a. Hematopoietic function: total white blood cell (WBC) count ≥3000/mm³, absolute neutrophil count (ANC) ≥1500/mm³, platelet count ≥75,000/mm³, hemoglobin ≥10 g/dL
    b. Hepatic function: bilirubin ≤1.5 × × the upper limit of normal (ULN) (excluding Gilberts Syndrome, for which bilirubin must be ≤4 × ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × ULN, and alkaline phosphatase ≤2.5 × ULN
    c. Renal function: serum creatinine ≤1.5 × ULN or for patients with creatinine levels above the ULN, estimated creatinine clearance of ≥60 mL/min, calculated using the Cockcroft- Gault equation35
    d. aPTT ≤1.5 × ULN
    13. Female patients of childbearing potential, and male study patients and their sexual partners of childbearing potential must agree to practice a highly effective method of contraception beginning at least 28 days before the start of treatment until at least 6 months after the last dose of study drug.
    a. A woman of childbearing potential is defined as a woman who is not permanently sterilized or postmenopausal. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.
    b. Women of childbearing potential must have a negative serum or urine pregnancy test.
    c. A highly effective method of birth control is defined as one which results in a low failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or vasectomized partner. [...]
    14. Patients with prior malignancies must be disease-free for ≥5 years. However curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; or prostate cancer curatively treated at the time of screening is allowed.
    1. Consentimiento informado por escrito[...]
    2. Tener al menos 18 años.
    3. Diagnóstico confirmado de GBM segun revisión local del tejido tumoral de la biopsia inicial, un procedimiento quirúrgico o una nueva extirpación. Informe patológico formal que confirme un GBM aceptable.
    4. GBM recidivante com la evaluación RANO, confirmado por una revisión central siguiente: se requiere una enfermedad medible con pruebas inequívocas documentadas de recidiva o progresión tras el tratamiento previo (ej. aumento del 25 % en la suma de los diámetros perpendiculares de las lesiones con realce de contraste con dosis estables o crecientes de corticosteroides; pero estos no pueden ser cambios en la dosis de corticosteroides) según documentado por el investigador.
    5. El tumor se localiza en la región supratentorial.
    6. La lesión (o suma de lesiones) no supera los 50 cm3 de volumen.
    7. El estado de metilación (MGMT) debe estar disponible; los resultados obtenidos con los métodos para las pruebas de metilación de la MGMT (ej. PCR específica para metilación o PCR cuantitativa) son aceptables.
    8. No más de 1 línea de tratamiento previa (ej. una intervención quirúrgica seguida de radiación con quimioterapia concomitante, seguida de quimioterapia adyuvante se considera una línea de tratamiento). Se acepta la realización de un procedimiento quirúrgico de citorreducción secundaria durante la primera línea de tratamiento. Asimismo, también se acepta la terapia de campo de tumores (TTFields; Optune) si se administra como tratamiento de primera línea.
    9.Recuperación de la toxicidad/efectos secundarios de todas las terapias anteriores hasta un grado 1 o inferior, sujeto a opinion del investigador, salvo alopecia. Se requieren los siguientes intervalos de tiempo con respecto a los previos para considerar al paciente elegible:
    a)12semanas tras finalizar la radioterapia (para reducir el riesgo de pseudoprogresión), a menos que se confirme la progresión con una biopsia
    b)4 semanas tras finalizar otra quimioterapia anterior o 6 semanas después del fin del tratamiento con nitrosoureas
    c)4 semanas a partir del fin de cualquier terapia TTFields
    d)4 semanas a partir de cualquier cirugía mayor (cirugía citorreductora máxima, o resección total macroscópica o resección parcial) o lesión traumática significativa yAdemás, cualquier incisión o herida quirúrgica debe estar curada por completo
    10.Una dosis estable o decreciente de corticosteroides (o ninguna) para el tratamiento del edema cerebral durante al menos 5 días antes de la realización de la RMN inicial y de la inclusión en el estudio para documentar la PE, para que los cambios observados en la RMN no estén relacionados con el empleo de corticosteroides
    11.Las terapias inmunosupresoras permitidas incluyen el uso de glucocorticoides tópicos, inhalados, oftálmicos o intraarticulares, o el uso de dosis de reemplazo fisiológico de glucocorticoides
    12.El paciente reúne los criterios necesarios para recibir quimioterapia al presentar una función orgánica y de la médula ósea adecuadas en las 2 semanas previas al inicio del tratamiento del estudio, según lo definido a continuación y sujeto a opinion del investigador: a)Función hematopoyética: recuento total de leucocitos ≥3000/mm³, recuento absoluto de neutrófilos ≥1500/mm³, recuento de plaquetas ≥75.000/mm³ y Hg≥10/dl. b)Función hepática: de bilirrubina ≤1,5x el límite superior de la normalidad (LSN) (excepto en el síndrome de Gilbert, en cuyo caso de bilirrubina debe ser ≤4 veces el LSN), de aspartato aminotransferasa(AST) y alanina aminotransferasa (ALT) <3x el LSN y de fosfatasa alcalina ≤2,5x el LSN. c)Función renal: creatinina sérica ≤1,5x el LSN o en pacientes con la creatinina>LSN, un aclaramiento de creatinina estimado de ≥60 ml/min, calculado mediante la fórmula de Cockroft-Gault. d) aPTT ≤1,5 veces el LSN.
    13. Pacientes en edad fertil, y los pacientes varones del estudio y sus parejas en edad fertil, deben aceptar utilizar un método anticonceptivo de alta eficacia como mínimo 28 días antes del inicio del tratamiento y hasta al menos 6 meses después de la última dosis del fármaco en estudio
    a)Una mujer en edad fertil es una mujer que no está esterilizada de manera permanente ni es posmenopáusica. La posmenopausia ses un período de 12 meses sin menstruación sin una causa médica alternativa.b)Las mujeres en edad fertil deben obtener un resultado (-) en un test de embarazo en suero u orina.c)Un método anticonceptivo de alta eficacia es aquel con una tasa baja de fallo en uso constante y correcta, como implantes, anticonceptivos inyectables, anticonceptivos orales combinados, algunos DIUS, abstinencia sexual o vasectomía masculina [...]
    14.Pacientes con neoplasias malignas deben haber estado sin de enfermedad durante ≥5 años. Pero, se acepta un diagnóstico de carcinoma de piel de células basales o escamosas; carcinoma in situ de cuello uterino, mama o vejiga; o cáncer de próstata tratado con fines curativos en la selección.
    E.4Principal exclusion criteria
    1. Unable or not willing to comply with the protocol regulations.
    2. Any additional concurrent radiation therapy or chemotherapy (including but not limited to TMZ) for recurrent or progressive GBM after a first line treatment.
    3. Prior treatment with bevacizumab.
    4. Prior treatment with lomustine.
    5. Screening MRI showing a mass effect defined as significant compression of the ventricular system and/or a midline shift (≥10 mm)34 confirmed by central MRI review.
    6. 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 or altered mental status.
    7. Presence of poorly controlled seizures, defined as occurring despite SOC or requiring hospitalization.
    8. Prior anthracycline cumulative dose more than 550 mg/m2.
    9. Heart disease:
    a. LVEF <50%
    b. Unstable angina
    c. CHF with New York Heart Association (NYHA) classification of 3 or 4
    d. Patients with baseline QT/QTc interval >480 msec, a history of additional risk factors for torsades de pointes (TdP) (eg, heart failure, hypokalemia, family history of long QT syndrome) and using concomitant medications that significantly prolong the QT/QTc interval
    e. History of myocardial infarction within 12 months of enrollment
    10. Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg and/or diastolic BP >100 mmHg).
    11. Known to be positive for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV), human immunodeficiency virus (HIV), 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).
    12. 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.
    1. Incapacidad o falta de disposición para cumplir las normas del protocolo.
    2. Cualquier radioterapia o quimioterapia simultánea adicional (incluida, entre otras, la temozolomida) para la GBM recidivante o progresiva después de un tratamiento de primera línea.
    3. Tratamiento previo con bevacizumab.
    4. Tratamiento previo con lomustina
    5. RMN de selección que muestre un efecto de masa, definido como compresión significativa del sistema ventricular o un desplazamiento de la línea media (≥10 mm), confirmado por la revisión central de la RMN.
    6. Cualquier trastorno (médico, social o psicológico) que impida el aporte de información y el seguimiento adecuados, incluidos, entre otros, trastornos psiquiátricos de relevancia clínica, incapacidad legal, demencia o un estado mental alterado.
    7. Presencia de convulsiones mal controladas, definidas como aquellas que ocurran a pesar de administrar un tratamiento estándar o que requieren hospitalización.
    8. Dosis previa acumulada de antraciclina superior a 550 mg/m2. Puede consultarse más información detallada en el Apéndice 2 del protocolo.
    9. Cardiopatía:
    a. FEVI <50 %.
    b. Angina inestable.
    c. Insuficiencia cardíaca congestiva con una clasificación de 3 o 4 según la New York Heart Association.
    d. Pacientes con un intervalo QT/QTc basal >480 ms, antecedentes de factores de riesgo adicionales para la taquicardia ventricular polimorfa en entorchado (p. ej., insuficiencia cardíaca, hipopotasemia o antecedentes familiares de síndrome de QT largo) y que consuman medicamentos concomitantes que prolongan de manera significativa el intervalo QT/QTc.
    e. Antecedentes de infarto de miocardio en los 12 meses anteriores a la inclusión en el estudio
    10. Hipertensión incontrolada (presión arterial [PA] sistólica >150 mmHg o PA diastólica >100 mmHg)
    11. Diagnóstico positivo para el antígeno de superficie del virus de la hepatitis B, el virus de la hepatitis C, el virus de la inmunodeficiencia humana, la enfermedad por coronavirus 2019 (COVID-19 [positivo en el momento de la selección]) o cualquier otra infección vírica, bacteriana o fúngica aguda (no tienen que realizarse pruebas a menos que exista una enfermedad sintomática o sospecha de enfermedad)
    12. A menos que lo apruebe el promotor, los pacientes que presenten cualquier otra afección médica intercurrente incontrolada, incluidos, entre otros, diabetes mellitus o enfermedad pulmonar obstructiva crónica, que no hayan podido controlarse con tratamiento médico durante los 3 meses previos, no podrán participar en el estudio.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is OS.
    Criterio principal de valoración de este estudio es SG.
    E.5.1.1Timepoint(s) of evaluation of this end point
    through study completion, an average of 4 years
    Hasta la finalización del estudio, un promedio de 4 años
    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 or PR per RANO criteria
    • DCR, defined as CR or PR or 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.
    • SLP, definida como el período de tiempo transcurrido desde el inicio de la administración del fármaco en estudio hasta la progresión de la enfermedad según los hallazgos de una RMN.
    • SLEv, definida como el período de tiempo transcurrido desde el inicio de la administración del fármaco en estudio hasta la progresión de la enfermedad, la muerte o lainterrupción del tratamiento por cualquier motivo (p. ej., toxicidad, intolerancia, afecciones relacionadas con la enfermedad o falta de respuesta).
    • TRO, definida como una RC o RP según los criterios RANO.
    • TCE, definida como una RC o RP, o bien una EE, según los criterios RANO. Una EE se define como una ausencia de progresión de la enfermedad según los hallazgos de una RMN realizada al menos 6 semanas después del inicio del tratamiento.
    El criterio de valoración FC de este estudio:
    Parámetros FC estándar para la berubicina y su metabolito, el berubicinol, derivados del análisis no compartimental de la concentración plasmática del fármaco frente al tiempo.
    E.5.2.1Timepoint(s) of evaluation of this end point
    through study completion, an average of 4 years
    Hasta la finalización del estudio, un promedio de 4 años
    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 concerned3
    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 No
    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
    Italy
    Netherlands
    Spain
    Switzerland
    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
    UVUP
    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 years3
    E.8.9.2In all countries concerned by the trial months2
    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 state24
    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
    El tratamiento o asistencia sanitaria después de que el sujeto haya terminado de participación en el ensayo no será diferente de lo esperado en un tratimiento normal para la condición objeto de este estudio.
    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 Decision2022-01-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-12-28
    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