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   43887   clinical trials with a EudraCT protocol, of which   7297   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:2019-000790-23
    Sponsor's Protocol Code Number:AN2025H0301
    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:2021-09-01
    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 number2019-000790-23
    A.3Full title of the trial
    The BURAN Study of Buparlisib (AN2025) In Combination with Paclitaxel Compared to Paclitaxel Alone, in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
    Estudio BURAN sobre buparlisib (AN2025) en combinación con paclitaxel frente a paclitaxel en monoterapia, para pacientes con carcinoma de células escamosas de cabeza y cuello recurrente o metastásico
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The BURAN Study of Buparlisib (AN2025) In Combination with Paclitaxel Compared to Paclitaxel Alone in patients with head and neck cancer
    Estudio BURAN sobre buparlisib (AN2025) en combinación con paclitaxel comparado con Paclitaxel solamente en pacientes con cancer de cabeza y cuello
    A.3.2Name or abbreviated title of the trial where available
    The BURAN Study
    Estudio BURAN
    A.4.1Sponsor's protocol code numberAN2025H0301
    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 SponsorAdlai Nortye USA 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 supportAdlai Nortye USA Inc.,
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAdlai Nortye USA Inc.,
    B.5.2Functional name of contact pointKevin Dreyer
    B.5.3 Address:
    B.5.3.1Street Address685 US-1,
    B.5.3.2Town/ cityNorth Brunswick Township, NJ
    B.5.3.3Post code08902
    B.5.3.4CountryUnited States
    B.5.6E-mailKevin.Dreyer@adlainortye.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 nameBuparlisib
    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 INNBUPARLISIB
    D.3.9.1CAS number 944396-07-0
    D.3.9.2Current sponsor codeAN2925
    D.3.9.3Other descriptive nameBUPARLISIB
    D.3.9.4EV Substance CodeSUB128477
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 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 nameBuparlisib
    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 INNBUPARLISIB
    D.3.9.1CAS number 944396-07-0
    D.3.9.2Current sponsor codeAN2925
    D.3.9.3Other descriptive nameBUPARLISIB
    D.3.9.4EV Substance CodeSUB128477
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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: 3
    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 Paclitaxel
    D.2.1.1.2Name of the Marketing Authorisation holderEbewe Pharma Ges.m.b.H. Nfg. KG
    D.2.1.2Country which granted the Marketing AuthorisationBulgaria
    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 namePaclitaxel
    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.3.8INN - Proposed INNPaclitaxel
    D.3.9.1CAS number 33069-62-4
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number30 to 300
    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
    Head and Neck Squamous Cell Carcinoma (HNSCC)
    Carcinoma de células escamosas de cabeza y cuello (CCECC)
    E.1.1.1Medical condition in easily understood language
    Head and Neck Cancer
    Cancer de cabeza y cuello
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is as follows:
    • To assess the overall survival (OS) of buparlisib in combination with paclitaxel compared to paclitaxel alone in patients with refractory, recurrent, or metastatic HNSCC.
    El objetivo principal del estudio es el siguiente:
    • Evaluar la supervivencia global (SG) del buparlisib en combinación con paclitaxel, frente a paclitaxel en monoterapia en pacientes con CCECC refractario, recurrente o metastásico.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are as follows:
    • To evaluate additional efficacy parameters: progression free survival (PFS), ORR, and DoR, by the Investigator and Independent Radiological Review Committee (IRRC).
    • To evaluate efficacy parameters in subgroups of patients defined by the randomization strata.
    • To assess the effect of buparlisib in combination with paclitaxel on patient’s symptoms and health-related quality of life (HRQoL).
    • To assess biomarkers of response to buparlisib in combination with paclitaxel.
    • To assess the pharmacokinetics (PK) of buparlisib in combination with paclitaxel.
    Los objetivos secundarios del estudio son los siguientes:
    • Evaluar los parámetros de eficacia adicionales: supervivencia sin progresión (SSP), TRG y DR, por parte del investigador y del Comité de Revisión Radiológica Independiente (CRRI).
    • Evaluar los parámetros de eficacia en subgrupos de pacientes definidos por los estratos de aleatorización.
    • Evaluar el efecto del buparlisib en combinación con paclitaxel sobre los síntomas del paciente y la calidad de vida relacionada con la salud (CdVRS).
    • Evaluar los biomarcadores de la respuesta al buparlisib en combinación con paclitaxel.
    • Evaluar la farmacocinética (FC) del buparlisib en combinación con paclitaxel.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients must meet the following criteria to be eligible for enrollment into the study:
    1. Aged ≥18 years old.
    2. Able to provide informed consent obtained before any study related activities and according to local guidelines.
    3. Patient has histologically and/or cytologically-confirmed HNSCC.
    4. Patient has archival or new tumor tissue for the analysis of biomarkers. One tumor block (preferred) or a minimum of 12 (15 recommended) unstained slides to be provided. Enrollment in the study is contingent on confirmation of an adequate amount of tumor tissue. Patients progressing following treatment with an anti PD 1/anti PD L1 therapy are encouraged to have a new tumor biopsy for biomarker analysis (optional).
    5. Patient has either progressive or recurrent disease after treatment with PDL1/PD1 based therapy for recurrent or metastatic disease:
    a. PDLl/PD1 therapy alone for metastatic (monotherapy) disease
    b. PDL1/PD1 in combination with chemotherapy for metastatic and recurrent disease
    c. PDL1/PD1 used for metastatic disease, after or prior to receiving a platinum agent for locally advanced or metastatic disease.
    6. Patient has received no more than two prior lines of systemic treatment for HNSCC (single agent chemotherapy used as a radiosensitizer is not counted as a prior line of therapy).
    7. Patient has measurable disease as determined per RECIST version 1.1. If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a four-week period since radiotherapy completion is required.
    8. Patient has adequate bone marrow function and organ function as shown by the following:
    a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
    b. Hemoglobin ≥ 9 g/dL (which may be reached by transfusion).
    c. Platelets ≥ 100 x 109/L (which may be reached by transfusion).
    d. International normalized ratio (INR) ≤ 1.5.
    e. Calcium (corrected for serum albumin) within normal limits (WNL) or ≤ grade 1 severity according to NCI-CTCAE version 5.0 if judged clinically not significant by the Investigator. Patients concomitantly taking bisphosphonates or denosumab for calcium correction are eligible.
    f. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ 1.5 x upper limit of normal (ULN) or < 3.0 x ULN if liver metastases are present.
    g. Total serum bilirubin ≤ ULN or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin below or within normal range in patients with well documented Gilbert’s Syndrome. Gilbert’s syndrome is defined as presence of episodes of unconjugated hyperbilirubinemia with normal results from cells blood count (including normal reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease processes at the time of diagnosis.
    h. Serum creatinine ≤ 1.5 x ULN or calculated or directly measured creatinine clearance (CrCL) > 30 mL/min.
    I. Haemoglobin A1c (glycosylated hemoglobin; HbA1c) ≤8%.
    9. Patient has Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
    10. Patient is able to swallow and retain oral medication. Patients able to swallow oral medication but mostly self-nourished through gastric or jejunal feeding tube are eligible.
    11. Patients must apply highly effective contraception during and throughout the study, as well after the final dose of study treatment, as detailed below:
    a. Men should use an effective method of contraception and not father a child during the study and for the six-month period after treatment. Men are recommended to seek advice on conservation of sperm prior to treatment with paclitaxel as per product label.
    b. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use a highly effective contraceptive during the study and for at least four weeks after the final dose of study treatment or as specified in the local prescription guidelines for paclitaxel (e.g., for six months after final dose of paclitaxel according to the product insert/Summary of Product Characteristics [SmPC] from France and United Kingdom).
    c. Highly effective contraception is defined as either:
    o Total abstinence: When this is in line with the preferred and usual lifestyle of the patient.
    o Female sterilization: When the female study patient has had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
    o Male partner sterilization. For female study patients, the vasectomized male partner should be the sole partner for that patient.
    o Using a combination of the following (both apply):
    Placement of an IUD or IUS, and barrier methods of contraception
    Los pacientes deben cumplir los siguientes criterios para la inclusión en el estudio:
    1. Tener ≥ 18 años de edad.
    2. Se capaces de prestar consentimiento informado obtenido antes de cualquier actividad relacionada con el estudio y de acuerdo con las pautas locales.
    3. Tener CCECC histológica y/o citológicamente confirmado.
    4. Tener tejido tumoral nuevo o en archivo para el análisis de biomarcadores. Se debe suministrar un bloque del tumor (de preferencia) o un mínimo de 12 (15, recomendado) preparaciones sin teñir. La inclusión en el estudio depende de la confirmación de una cantidad adecuada de tejido tumoral. Se recomienda para los pacientes en los que se observe progresión después del tratamiento con una terapia tratamiento anti-PD-1/anti-PD-L1 que se les realice una nueva biopsia del tumor para el análisis de biomarcadores (opcional).
    5. Tener una enfermedad progresiva o recurrente después del tratamiento basado en PDL1/PD1 para enfermedad recurrente o metastásica:
    a. Terapia con PDL1/PD1 en monoterapia para enfermedad metastásica
    b. PDL1/PD1 en combinación con quimioterapia para enfermedad metastásica y recurrente
    c. PDL1/PD1 utilizados para enfermedad metastásica, después o antes de recibir un agente de platino para enfermedad localmente avanzada o metastásica.
    6. Haber recibido no más de dos líneas previas de tratamiento sistémico para CCECC.
    7. Tener una enfermedad mensurable según se V1.1 de RECIST. Si el único sitio de enfermedad mensurable es una lesión previamente irradiada, se requiere progresión documentada de la enfermedad y un período de cuatro semanas desde la finalización de la radioterapia.
    8. Tener función de la médula ósea y función orgánica adecuadas, según:
    a. Recuento absoluto de neutrófilos (RAN) ≥ 1,5 veces 109/l.
    b. Hemoglobina ≥ 9 g/dl (que se puede alcanzar mediante transfusión).
    c. Plaquetas ≥ 100 veces 109/l (que se puede alcanzar mediante transfusión).
    d. Índice internacional normalizado (INR) ≤ 1,5.
    e. Calcio (corregido para albúmina sérica) dentro de los límites normales (DLN) o con gravedad de grado ≤ 1 según la versión 5.0 de NCI-CTCAE si el investigador la considera no clínicamente significativa. Los pacientes que toman bifosfonatos o denosumab de manera concomitante para la corrección del calcio reúnen los requisitos.
    f. Alanina aminotransferasa (AST) y aspartato aminotransferasa (ALT) ≤ 1,5 veces el límite superior de lo normal (LSN) o < 3,0 veces el LSN si se presentan metástasis hepáticas.
    g. Bilirrubina sérica total ≤ el LSN o ≤ 1,5 veces el LSN si se presentan metástasis hepáticas; o bilirrubina total ≤ 3,0 veces el LSN con bilirrubina directa por debajo o dentro del rango normal en pacientes con síndrome de Gilbert bien documentado. Resultados normales de pruebas de la función hepática y ausencia de otros procesos de la enfermedad contribuyentes en el momento del diagnóstico.
    h. Creatinina sérica ≤ 1,5 veces el LSN o aclaramiento de creatinina (AcCr) calculada o directamente medida > 30 ml/min.
    i. Hemoglobina A1C (hemoglobina glicosilada; HbA1c) ≤ 8 %.
    9. Tener estado funcional del Grupo Oncológico Cooperativo del Este (ECOG) ≤1.
    10. Poder tragar y retener el medicamento oral. Poder ingerir medicación oral, pero reúnen los requisitos aquellos que se autonutran principalmente a través de un tubo de alimentación gástrica o yeyunal, son elegibles.
    11. Los pacientes deben utilizar métodos
    nticonceptivos altamente eficaces durante y a lo largo del estudio, así como después de la dosis final del tratamiento del estudio, como se detalla a
    continuación:
    a. Los hombres deben usar un método anticonceptivo eficaz y no engendrar a un hijo durante el estudio y durante el período de seis meses después del tratamiento.
    b. Las mujeres fértiles, deben usar un anticonceptivo altamente eficaz durante el estudio y durante al menos cuatro semanas después de la dosis final del tratamiento del estudio o según lo especifiquen las pautas locales de prescripción para paclitaxel.
    c. Cualquiera de los siguientes son métodos anticonceptivos altamente eficaces:
    o Abstinencia total: cuando esto esté en consonancia con el estilo de vida preferido y habitual del paciente.
    o Esterilización femenina: cuando la paciente se ha sometido a una ooforectomía bilateral quirúrgica (con o sin histerectomía) o ligadura de trompas al menos seis semanas antes de tomar el tratamiento del estudio. En caso de solo ooforectomía, únicamente cuando se haya confirmado el estado reproductivo de la mujer mediante una evaluación de nivel hormonal de seguimiento.
    o Esterilización de pareja masculina. Para pacientes del estudio de sexo femenino, la pareja de sexo masculino con vasectomía debe ser la única pareja para esa paciente.
    Uso de una combinación de lo siguiente (ambos corresponden):
    o Colocación de un DIU o un sistema intrauterino (SIU).
    o Métodos anticonceptivos de barrera: preservativo o tapón oclusivo con espuma/gel/película/crema espermicida/supositorio vaginal.
    E.4Principal exclusion criteria
    Patients meeting any of the following criteria will not be eligible for participation in the study:
    1. Patient has received previous treatment with any protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR) inhibitors, or phosphatidylinositol 3 kinase (PI3K) pathway inhibitors.
    2. Patient received treatment with a taxane as part of prior treatment for metastatic disease.
    3. Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this study. Patient must have completed any prior local treatment for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy) and must be on a stable low dose of corticosteroid therapy. Radiosurgery must have been completed at least 14 days prior to start of study treatment.
    4. Patient has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study treatment or who have adverse events which have not recovered to grade 1 or better from previous chemotherapy treatment (except alopecia, autoimmune endocrine events must be stable and controlled).
    5. Patient has grade ≥ 2 neuropathy, colitis, pneumonitis, elevated HbA1C, and uncontrolled endocrinopathies from previous treatment.
    6. Patient has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects.
    7. Patient is currently receiving increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent. The following uses of corticosteroids are permitted: single doses; standard premedication for paclitaxel, topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops, or local injections (e.g., intra-articular), or < 10 mg prednisolone or equivalent.
    8. Patient is being treated at start of study treatment with any of the following drugs:
    a. Drugs known to be strong or moderate inhibitors or inducers of isoenzyme cytochrome P450 3A4 (CYP3A4) including herbal medications. b. Drugs with a known risk of inducing Torsades de Pointes.
    9. Patient is currently receiving warfarin or other coumarin-derived anti-coagulant, for treatment, prophylaxis, or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), fondaparinux or new oral anticoagulants (NOACs) is allowed.
    10. Patient has a known hypersensitivity and/or contraindication to paclitaxel, standard premedication for paclitaxel, or other products containing Cremophor®.
    11. Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the Investigator’s judgment, contraindicate patient participation in the clinical study.
    12. Patient has a known history of HIV infection (testing not mandatory).
    13. Patient has any of the following cardiac abnormalities:
    a.Symptomatic congestive heart failure within 12 months of the screening period , History of documented congestive heart failure or documented cardiomyopathy and left ventricular ejection fraction (LVEF) <50% as determined by multiple gated acquisition (MUGA) scan or ECHO, Myocardial infarction ≤six months prior to enrollment, Unstable angina pectoris, Serious uncontrolled cardiac arrhythmia, Symptomatic pericarditis, QT interval corrected according to the formula of Fridericia (QTcF) > 450 msec for males and > 470 msec for females, on the screening ECG, Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment.
    14. Patient has impairment of GI function or GI disease that may significantly alter the absorption of study treatment.
    15. Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation or active severe personality disorders are not eligible. 16. Patient has other prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, early gastric or GI cancer resected completely by endoscopy procedures or any other cancer from which the patient has been disease free for ≥ 3years.
    17. Patient has a history of non-compliance to any medical regimen or inability to grant consent.
    18. Patient is concurrently using or has used another approved or investigational cancer agent within 4 weeks of the screening period.
    19. Patient is pregnant or nursing (lactating). Patients with elevated human chorionic gonadotrophin (hCG) at baseline that is judged to be related to the tumor are eligible if hCG levels do not show the expected doubling when repeated five to seven days later, or pregnancy has been ruled out by vaginal ultrasound
    Los pacientes que cumplan cualquiera de los siguientes criterios no serán aptos:
    1. Haber recibido tratamiento previo con cualquier proteína quinasa B (FCB/AKT), inhibidores de blanco de la rapamicina en mamíferos (mTOR) o inhibidores de la vía de fosfatidilinositol 3-quinasa (PI3K).
    2. Haber recibido tratamiento con taxano como parte tratamiento previo para enfermedad metastásica.
    3. Tener metástasis sintomática del sistema nervioso central. Pacientes con metástasis asintomática del SNC pueden participar. Haber completado cualquier tratamiento local previo para metástasis del SNC ≥ 28 días antes inicio de tratamiento y estar en dosis baja estable de tratamiento con corticosteroides. Radiocirugía completada al menos 14 días antes iniciar tratamiento.
    4. Haber recibido radioterapia de campo extendido ≤ 4 semanas o radiación de campo limitado como paliativo ≤ 2 semanas antes de iniciar el tratamiento o acontecimientos adversos no recuperados a grado 1 o un grado mejor del tratamiento de quimioterapia previo (excepto alopecia, eventos endocrinos autoinmunes deben estar estables y controlados).
    5. Tener neuropatía de grado ≥ 2, colitis, neumonitis, HbA1C elevada y endocrinopatías no controladas del tratamiento previo.
    6. Haber sido sometido a cirugía mayor dentro de los 14 días previos a inicio de tratamiento o no se ha recuperado de efectos secundarios principales.
    7. Recibir tratamiento crónico o en aumento (> 5 días) con corticosteroides u otro agente inmunosupresor. Se permiten usos de corticosteroides: dosis únicas; medicación previa estándar para paclitaxel, aplicaciones tópicas, aerosoles inhalados, gotas para ojos o inyecciones locales o < 10 mg de prednisolona o equivalente.
    8. Recibir tratamiento al inicio del tratamiento del estudio con cualquiera de los siguientes fármacos:
    a. Fármacos conocidos como inhibidores o inductores fuertes o moderados de la isoenzima citocromo P450 3A4 (CYP3A4), incluidos medicamentos a base de hierbas.
    b. Fármacos con riesgo conocido de inducción de Torsades de Pointes.
    9. Recibir warfarina u otro anticoagulante derivado de cumarina, para tratamiento, profilaxis o otro motivo. Se permite el tratamiento con heparina, heparina de bajo peso molecular, fondaparinux o nuevos anticoagulantes orales.
    10. Tener hipersensibilidad o contraindicación conocida a paclitaxel, medicación previa estándar para paclitaxel u otros productos que contengan Cremophor.®.
    11. Tener otras afecciones médicas graves o no controladas concurrentes que a criterio del investigador, contraindican la participación en el estudio.
    12. Tener antecedentes conocidos de infección por VIH.
    13. Tener cualquiera siguientes anomalías cardíacas:
    a. Insuficiencia cardíaca congestiva sintomática dentro de los 12 meses anteriores al período de selección.
    b. Antecedentes insuficiencia cardíaca congestiva documentados o cardiomiopatía documentada y una fracción de eyección del ventrículo izquierdo < 50 % según la determinación de la angiografía radioisotópica o ecocardiograma.
    c. Infarto del miocardio ≤ seis meses antes de la inclusión.
    d. Angina de pecho inestable.
    e. Arritmia cardíaca grave no controlada.
    f. Pericarditis sintomática.
    g. Intervalo QT corregido con la fórmula de corrección de Fridericia > 450 ms para los varones y > 470 ms para las mujeres, en el electrocardiograma de selección.
    h. Recibir tratamiento con medicamento con riesgo conocido por prolongar el intervalo QT o inducir Torsades de Pointes, y el tratamiento no se puede interrumpir o cambiar a un medicamento diferente antes de comenzar el tratamiento del estudio.
    14. Tener trastorno de función gastrointestinal (GI) o enfermedad GI que puede alterar significativamente la absorción del tratamiento.
    15. Tener antecedentes médicamente documentados de o un episodio depresivo mayor activo, trastorno bipolar (I o II), trastorno obsesivo compulsivo, esquizofrenia, antecedente de intento o ideación suicida o ideación homicida o trastornos de personalidad activos severos.
    16. Tener otros tumores malignos previos o concurrentes, excepto: cáncer de piel células escamosas o basales adecuadamente tratado, u otro cáncer in situ adecuadamente tratado, cáncer gástrico o GI temprano con resección completa mediante procedimientos de endoscopía o cualquier otro cáncer del cual el paciente ha estado libre de enfermedad durante ≥ 3 años.
    17. Tener antecedentes de incumplimiento de cualquier régimen médico o inhabilidad para otorgar el consentimiento.
    18. Estar utilizando concurrentemente o ha usado otro agente oncológico aprobado o en fase de investigación dentro de las 4 semanas del período selección.
    19. Estar embarazada o amamantando. Pacientes con gonadotropina coriónica humana elevada (hCG) en período de referencia considera relacionada con el tumor reúnen los requisitos si los niveles de hCG no muestran duplicación esperada cuando se repiten entre cinco y siete días después, o se ha descartado embarazo mediante ultrasonido vaginal.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is OS for the entire (Intent-to-Treat [ITT]) population of patients. The interim endpoint of the study is ORR on a subset of patients with at least six months follow up at the time the last patient is enrolled
    El criterio principal de valoración de este estudio es la SG para la totalidad de la población (intención de tratar [ITT]) de los pacientes. El criterio provisionales de valoración del estudio es la TRG en un subconjunto de pacientes con al menos seis meses de seguimiento al momento en que se incluye al último paciente.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary statistical analysis of the study will be based on OS data from all patients once 383 events (deaths) have occurred. This analysis is expected to occur when all patients have either discontinued from the study or been followed for a minimum of 12 months
    El análisis estadístico primario del estudio se basará en los datos de la SG de todos los pacientes una vez que se hayan producido 383 eventos (muertes). Se espera que este análisis ocurra cuando todos los pacientes hayan interrumpido el estudio o hayan recibido seguimiento durante un mínimo de 12 meses.
    E.5.2Secondary end point(s)
    The secondary endpoints of this study are as follows:
    Efficacy:
    • PFS
    • Overall response rate (ORR)
    • Duration of response (DoR)
    • Change from baseline in the global health status/Quality of life (QOL) and pain scale scores of the EORTC QLQ-C30, respectively.
    • Time to definitive 10% deterioration in the global health status/QOL and pain scale scores of the EORTC QLQ-C30, respectively.
    • EQ-5D-5L
    • Biomarkers
    Safety:
    • AEs
    • Clinical laboratory tests
    • PHQ-9
    • GAD-7
    Los criterios secundarios de valoración de este estudio son los siguientes:
    Eficacia:
    • SSP
    • Tasa de respuesta global (TRG)
    • Duración de la respuesta (DR)
    • Cambio desde el período de referencia en el estado de salud global/calidad de vida (CdV) y las puntuaciones de la escala de dolor del EORTC QLQ-C30, respectivamente.
    • Tiempo hasta el deterioro definitivo del 10 % en el estado de salud global/CdV y las puntuaciones de la escala de dolor del EORTC QLQ-C30, respectivamente.
    • EQ-5D-5L
    • Biomarcadores
    Seguridad:
    • AA
    • Pruebas de laboratorio clínico
    • PHQ-9
    • GAD-7
    E.5.2.1Timepoint(s) of evaluation of this end point
    All secondary analyses will be reported by treatment arm and analyses will be based on the ITT Population. PFS and DoR will be analyzed using the same methods as for the primary endpoint of OS. ORR will be analyzed using a Cochran-Mantel-Haenszel chi-square test with randomization factors as the strata.
    Safety summaries and analyses will be performed on the Safety population. Descriptive statistics will be presented to summarize the safety data.
    Todos los análisis secundarios se informarán por grupo de tratamiento y los análisis se basarán en la población ITT. La SSP y la DR se analizarán con los mismos métodos que para el criterio principal de valoración principal de la SG. Se analizará la TRG con una prueba de chi cuadrado de Cochran-Mantel-Haenszel con factores de aleatorización como estratos.
    Los resúmenes y análisis de seguridad se realizarán en la población de seguridad. Se presentarán estadísticas descriptivas para resumir los datos de seguridad
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA75
    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
    Australia
    Canada
    Japan
    Korea, Republic of
    Russian Federation
    Taiwan
    United States
    Belgium
    France
    Germany
    Hungary
    Italy
    Poland
    Spain
    United Kingdom
    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
    Last visit of last subject
    Ultima visita del ultimo sujeto
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    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: 276
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 206
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 249
    F.4.2.2In the whole clinical trial 489
    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)
    Patients will revert to their normal standard of care
    Los pacientes volverán a su practica clinica habitual.
    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 Decision2021-05-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-05-11
    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