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    Summary
    EudraCT Number:2015-003385-84
    Sponsor's Protocol Code Number:RXDX-101-02
    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:2016-02-03
    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 number2015-003385-84
    A.3Full title of the trial
    AN OPEN-LABEL, MULTICENTER, GLOBAL PHASE 2 BASKET STUDY OF ENTRECTINIB FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS THAT HARBOR NTRK1/2/3, ROS1, OR ALK GENE REARRANGEMENTS
    Estudio Cesto, abierto, multicéntrico, global, en fase II con Entrectinib para el tratamiento de pacientes con tumores sólidos localmente avanzados o metastásicos que albergan reordenaciones en los genes NTRK1/2/3, ROS1 o ALK
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of Tumor Alterations Responsive to Targeting Receptor Kinases-2
    Estudio de las alteraciones tumorales de respuesta a quinasas receptoras-2
    A.3.2Name or abbreviated title of the trial where available
    STARTRK-2
    STARTRK-2
    A.4.1Sponsor's protocol code numberRXDX-101-02
    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 SponsorIgnyta, 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 supportIgnyta Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIgnyta, Inc.
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street Address11111 Flintkote Avenue
    B.5.3.2Town/ citySan Diego, CA
    B.5.3.3Post code92121
    B.5.3.4CountryUnited States
    B.5.4Telephone number+3491732 80 002922
    B.5.5Fax number+3491750 01 93
    B.5.6E-mailecmaneval@ignyta.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 nameEntrectinib
    D.3.2Product code RXDX-101
    D.3.4Pharmaceutical form Capsule
    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 INNENTRECTINIB
    D.3.9.1CAS number 1108743-60-7
    D.3.9.2Current sponsor codeRXDX-101
    D.3.9.4EV Substance CodeSUB177830
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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
    Locally Advanced or Metastatic Solid Tumors that Harbor NTRK1/2/3, ROS1,
    or ALK Gene Rearrangements
    tumores sólidos localmente avanzados o metastásicos que albergan reordenaciones en los genes NTRK1/2/3, ROS1 o ALK
    E.1.1.1Medical condition in easily understood language
    Cancer that arises from organs and solid tissues which has spread to
    other organs
    El cáncer que surge de órganos y tejidos sólidos que se ha extendido a
    otros órganos
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10065147
    E.1.2Term Malignant solid tumor
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10065252
    E.1.2Term Solid tumor
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the objective response rate of entrectinib, as assessed by BICR, in each patient population basket of solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene rearrangement
    Determinar la tasa de respuesta objetiva (TRO) de entrectinib, evaluada por la BICR, en cada cesta de población de pacientes de tumores sólidos que presentan una reordenación en los genes NTRK1/2/3, ROS1 o ALK
    E.2.2Secondary objectives of the trial
    ?To determine the duration of response, time to response, and clinical benefit rate of entrectinib, in each patient population basket of solid tumors
    ?To determine the intracranial tumor response of entrectinib and CNS progression-free survival in patients presenting with measurable brain metastases at baseline
    ?To estimate the progression-free survival and overall survival of patients with solid tumors treated with entrectinib
    ?To evaluate the safety and tolerability of entrectinib when administered at the RP2D
    ?To assess the population pharmacokinetics (PK) of Entrectinib and to explore correlations between PK, response, and/or safety findings
    ?To evaluate the effect of entrectinib on ventricular repolarization
    ?To assess treatment-related symptoms and general health status using validated instruments of patient reported outcomes
    -Determinar la duración de la respuesta, el tiempo hasta la respuesta y la tasa de beneficio clínico de entrectinib, evaluada por la BICR, en cada cesta de población de pacientes de tumores sólidos
    -Determinar la respuesta del tumor intracraneal de entrectinib y la supervivencia sin progresión del SNC en pacientes que presenten metástasis cerebrales medibles en el momento inicial
    -Calcular la supervivencia sin progresión y la supervivencia general de los pacientes con tumores sólidos tratados con entrectinib
    -Evaluar la seguridad y la tolerabilidad de entrectinib cuando se administra en RP2D
    -Evaluar la farmacocinética (FC) de la población de entrectinib y explorar las correlaciones entre la FC, la respuesta o los hallazgos de seguridad?
    -Evaluar el efecto de entrectinib en la repolarización ventricular
    -Evaluar los síntomas relacionados con el tratamiento y el estado de salud general utilizando instrumentos validados de los resultados notificados de los pacientes
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement as determined by any nucleic acid-based diagnostic testing method (e.g., NGS, Sanger, RTPCR, NanoString, EdgeSeq; FISH is not an acceptable method) performed at a local CLIA-certified or equivalently-accredited diagnostic laboratory. Note: Patients diagnosed with anaplastic large cell lymphoma (ALCL) harboring a gene rearrangement of interest may be eligible provided they meet all other inclusion/exclusion criteria
    2. For patients enrolled via local molecular testing, an archival or fresh tumor tissue (unless medically contraindicated) is required to be submitted for independent central molecular testing at Ignyta?s CLIA laboratory post-enrollment
    3. Measurable disease as assessed locally using RECIST v1.1. Note: Patients with non-measurable disease (evaluable disease only) will be eligible for enrollment in the non-measurable disease basket and will mainly contribute to assessment of safety, PK, and other secondary endpoints.
    4. Patients with CNS involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previouslytreated and controlled, are allowed. The use of seizure prophylaxis is allowed as long as patients are taking non-enzyme-inducing anti-epileptic drugs (non-EIAEDs). If patients were previously on EIAEDs and these have been discontinued, they must have been discontinued for at least 2 weeks prior to the start of entrectinib treatment. If patients require an anti-epileptic medication, a CYP3A4 non-EIAED can be used such as levetiracetam, valproic acid, gabapentin, topiramate, or lacosamide. Moderate inducers of CYP450, such as dexamethasone or other glucocorticoids, may be used at the discretion of the Investigator. Patients requiring steroids must be at stable or decreasing doses for at least 2 weeks prior to the start of entrectinib treatment.
    5. Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements). Note: Prior treatment with crizotinib is permitted in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression.
    6. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior chemotherapy or small molecule targeted therapy, respectively, at the time of the start of Entrectinib treatment.
    7. At least 4 weeks must have elapsed since completion of antibody-directed therapy at the time of the start of Entrectinib treatment.
    8. Prior radiotherapy is allowed if more than 14 days have elapsed since the end of treatment. Patients who received brain irradiation must have completed whole brain radiotherapy at least 14 days prior and/or stereotactic radiosurgery at least 7 days prior to the start of entrectinib treatment.
    9. Age ? 18 years.
    10. Eastern Cooperative Oncology Group (ECOG) performance status ? 2.
    11. Adequate organ function as defined by the following criteria:
    ? Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) ? 3.0 × upper limit of normal (ULN); ? 5.0 × ULN if liver metastases are present
    ? Total serum bilirubin ? 2.0 × ULN; patients with a known history of Gilbert?s syndrome and/or isolated elevations of indirect bilirubin are eligible
    ? Serum creatinine within normal limits or creatinine clearance ? 30 mL/min
    12. Females of childbearing potential must have a negative serum pregnancy test during Screening and must not be breastfeeding or intending to become pregnant during the study.
    13. Ability to swallow entrectinib intact without chewing, crushing, or opening the capsules.
    14. Willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
    15. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to the start of Entrectinib treatment.
    1.Diagnóstico confirmado histológica o citológicamente de tumores sólidos localmente avanzados o metastásicos que presentan una reordenación en los genes NTRK1/2/3, ROS1 o ALK, determinada por un método de pruebas diagnósticas basadas en ácido nucleico (p. ej., NGS, Sanger, RT-PCR, NanoString, EdgeSeq; FISH no es un método aceptable) realizadas en un laboratorio local de diagnósticos certificado por CLIA o con acreditación equivalente.
    Nota: los pacientes diagnosticados con linfoma anaplásico de células grandes (anaplastic large cell lymphoma, ALCL) que albergan una reordenación en los genes de interés pueden ser aptos siempre que cumplan todos los otros criterios de exclusión/inclusión
    2.En el caso de los pacientes inscritos por prueba molecular local, debe presentarse tejido tumoral fresco o de archivo (a no ser que esté médicamente contraindicado) para las pruebas moleculares centrales independientes en el laboratorio CLIA de Ignyta después de la inscripción
    3.Enfermedad medible evaluada localmente con RECIST v1.1.
    Nota: los pacientes sin enfermedad medible (solo enfermedad evaluable) serán aptos para la inscripción en la cesta de enfermedad no medible y contribuirán principalmente a la evaluación de la seguridad, la FC y otros criterios de valoración secundarios.
    4.Se permitirá la inscripción de pacientes con afectación del SNC, incluida la carcinomatosis leptomeníngea, ya sea asintomática o si se ha tratado y controlado previamente. Se permite el empleo de profilaxis epiléptica siempre que los pacientes tomen antiepilépticos no inductores enzimáticos (no AEIE). Si los pacientes tomaban AEIE anteriormente y se ha interrumpido su administración, esta debe haberse interrumpido al menos 2 semanas antes del inicio del tratamiento con entrectinib. Si los pacientes requieren un antiepiléptico, se puede emplear un no AEIE de CYP3A4, como levetiracetam, ácido valproico, gabapentina, topiramato o lacosamida. Se podrán emplear inductores moderados de CYP450, como dexametasona u otros glucocorticoides, a discreción del investigador. Los pacientes que requieren corticoesteroides deben estar tomando dosis estables o decrecientes durante al menos 2 semanas antes del inicio del tratamiento con entrectinib.
    5. Se permite un tratamiento antineoplásico previo (excepto con inhibidores de Trk, ROS1 o ALK aprobados o en investigación en pacientes con tumores que alberguen dichas reordenaciones en los genes respectivos).
    Nota: el tratamiento previo con crizotinib se permite en pacientes con CPNM con reordenación de ALK o ROS1 que presentan solo progresión del SNC.
    6.Deben haber transcurrido al menos 2 semanas o 5 semividas, lo que dure menos, después de la quimioterapia o el tratamiento dirigido con moléculas pequeñas anterior, respectivamente, en el momento del inicio del tratamiento con entrectinib.
    7.Deben haber transcurrido al menos 4 semanas después de la finalización del tratamiento dirigido con anticuerpos en el momento del inicio del tratamiento con entrectinib.
    8.Se permite una radioterapia anterior si han transcurrido más de 14 días desde el final del tratamiento. Los pacientes que hayan recibido radiación cerebral deben haber completado la radioterapia cerebral al menos 14 días antes del inicio del tratamiento con entrectinib o, en el caso de radiocirugía estereotáctica, al menos 7 días antes.
    9.Edad ? 18 años.
    10.Estado general según el Grupo Oncológico Cooperativo del Este (Eastern Cooperative Oncology Group, ECOG) ? 2.
    11.Función orgánica adecuada definida según los criterios siguientes:
    ?-Aspartato aminotransferasa en suero (AST; transaminasa glutámico-oxaloacética sérica [serum glutamic oxaloacetic transaminase, SGOT]) y alanina aminotransferasa en suero (ALT; transaminasa glutámico-pirúvica sérica [serum glutamic pyruvic transaminase, SGPT]) ? 3,0 × límite superior de la normalidad (LSN); ? 5,0 × LSN si hay presencia de metástasis hepáticas
    ?-Bilirrubina sérica total ? 2,0 × LSN; son aptos los pacientes con antecedentes conocidos de síndrome de Gilbert o elevaciones aisladas de bilirrubina indirecta
    ?-Creatinina sérica en límites normales o aclaramiento de creatinina ? 30 ml/min
    12.Las mujeres en edad fértil deben obtener una prueba de embarazo en suero negativa durante la selección y no deben amamantar ni tener la intención de quedarse embarazadas durante el estudio.
    13.Capacidad de ingerir las cápsulas de entrectinib intactas sin masticarlas, partirlas ni abrirlas.
    14.Disponibilidad para cumplir con las visitas programadas, el plan de tratamiento, las pruebas analíticas y otros procedimientos del estudio.
    15.Documento de consentimiento informado firmado y fechado que indique que el paciente (o un representante legalmente aceptable) ha sido informado de todos los aspectos pertinentes del ensayo antes del inicio del tratamiento con entrectinib.
    E.4Principal exclusion criteria
    1. Current participation in another therapeutic clinical trial.
    2. Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements.
    Note: Prior treatment with crizotinib is permitted in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression.
    3. History of other previous cancer that would interfere with the determination of safety or efficacy of entrectinib with respect to the qualifying solid tumor malignancy.
    4. Incomplete recovery from any surgery prior to the start of entrectinib treatment that would interfere with the determination of safety or efficacy of entrectinib.
    5. Any condition (in the past 3 months) that would interfere with the determination of safety or efficacy of entrectinib: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, stroke, symptomatic bradycardia, or uncontrolled arrhythmias requiring medication.
    6. History of non-pharmacologically induced prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 500 milliseconds from ECGs performed at least 24 hours apart).
    7. History of additional risk factors for torsade de pointes (e.g., family history of long QT syndrome).
    8. Peripheral neuropathy Grade ? 2.
    9. Known active infections that would interfere with the assessment of safety or efficacy of entrectinib (bacterial, fungal, or viral, including human immunodeficiency virus positive).
    10. Active gastrointestinal disease (e.g., Crohn?s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption.
    11. Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
    12. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
    1.Participación simultánea en otro ensayo clínico terapéutico.
    2.Tratamiento previo con inhibidores de Trk, ROS1, o ALK aprobados o en investigación en pacientes con tumores que alberguen dichas reordenaciones en los genes respectivos.
    Nota: el tratamiento previo con crizotinib se permite en pacientes con CPNM con reordenación de ALK o ROS1 que presentan solo progresión del SNC.
    3.Antecedentes de otro cáncer anterior que pueda interferir con la determinación de la seguridad y la eficacia de entrectinib con respecto a la neoplasia maligna de tumor sólido que cumple los criterios.
    4.Recuperación incompleta de una cirugía anterior al inicio del tratamiento con entrectinib que pudiera interferir con la determinación de la seguridad y la eficacia de entrectinib.
    5.Cualquier enfermedad (en los últimos 3 meses) que pudiera interferir con la determinación de la seguridad o la eficacia de entrectinib: infarto de miocardio, angina inestable, injerto de derivación de la arteria coronaria/periférica, insuficiencia cardiaca congestiva sintomática, accidente vascular cerebral o ataque isquémico transitorio, derrame cerebral, bradicardia sintomática o arritmias no controladas que precisan medicación.
    6.Antecedentes de intervalo QTc prolongado no inducido de forma farmacológica (p. ej., demostración repetida de un intervalo QTc > 500 milisegundos en EGC realizados en intervalos de al menos 24 horas).
    7.Antecedentes de factores de riesgo adicionales de Torsade de pointes (p. ej., historial familiar de síndrome de QT largo).
    8.Neuropatía periférica de grado ? 2.
    9.Infecciones activas conocidas que puedan interferir con la evaluación de la seguridad o la eficacia de entrectinib (bacteriana, fúngica o viral, incluido ser positivo para el virus de la inmunodeficiencia humana).
    10.Enfermedad gastrointestinal activa (p. ej., enfermedad de Crohn, colitis ulcerosa o síndrome del intestino corto) u otro síndrome de malabsorción que pudiera afectar de forma razonable a la absorción del fármaco.
    11.Enfermedad pulmonar intersticial conocida, fibrosis intersticial o antecedentes de neumonía inducida por un inhibidor de la tirosina cinasa.
    12.Otra enfermedad médica o psiquiátrica grave, aguda o crónica, o anomalía analítica que pueda aumentar el riesgo asociado a la participación del estudio o la administración del fármaco del estudio o que pueda interferir con la interpretación de los resultados del estudio y, a juicio del investigador, haga que el paciente resulte inadecuado para su participación en este estudio o pueda comprometer los objetivos del protocolo en opinión del investigador y/o del promotor.
    E.5 End points
    E.5.1Primary end point(s)
    Objective Response Rate (ORR), defined as the proportion of
    patients with complete response (CR) or partial response (PR)
    Tasa de respuesta objetiva (TRO), definida como la proporción de pacientes con respuestas completas (RC) o parciales (RP)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Tumor assessments will be performed at Screening, at the end of Cycle 1 (Cycle 2 Day 1 +/- 2 days), every 8 weeks (+/- 7 days) thereafter, regardless of treatment delays resulting from toxicity, and at the End of Treatment (if more than 4 weeks have passed since the last imaging assessment).
    Evaluaciones tumorales se llevarán a cabo en la selección, al final del ciclo 1 (Ciclo 2 Día 1 +/- 2 días), cada 8 semanas (+/- 7 días) a partir de entonces a pesar de los retrasos de tratamiento que resultan de la toxicidad, y al final de tratamiento (si han pasado más de 4 semanas desde la última evaluación de imágenes).
    E.5.2Secondary end point(s)
    1.Duration of Response (DOR),
    2.Time to Response (TTR),
    3.Clinical Benefit Rate (CBR),
    4.Intracranial tumor response in patients with measurable brain metastases, as determined by BICR using RANO-BM
    5.CNS Progression-Free Survival (CNS-PFS) in patients with measurable brain metastases,
    6.Progression-Free Survival (PFS),
    7.Overall Survival (OS),
    8.Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities
    9.Population PK
    10.Ventricular repolarization
    11.Quality-of-life and health status
    1.Duración de la respuesta (DR)
    2.Tiempo hasta la respuesta (THR)
    3.Tasa de beneficio clínico (TBC)
    4.Respuesta tumoral intracraneal en pacientes con metástasis cerebrales medibles, según ha determinado la BICR con RANO-BM
    5.Supervivencia sin progresión del SNC (SSP-SNC) en pacientes con metástasis cerebrales medibles
    6.Supervivencia sin progresión (SSP)
    7.Supervivencia general (SG)
    8.Tipo, incidencia, intensidad, momento, gravedad y relación de los acontecimientos adversos y las anomalías analíticas
    9.FC de la población
    10.Repolarización ventricular
    11.Calidad de vida y estado de salud
    E.5.2.1Timepoint(s) of evaluation of this end point
    Tumor assessments will be performed at Screening, at the end of Cycle 1 (Cycle 2 Day 1 +/- 2 days), every 8 weeks (+/- 7 days) thereafter, regardless of treatment delays resulting from toxicity, and at the End of Treatment (if more than 4 weeks have passed since the last imaging assessment).
    Clinical Benefit Rate - 6 months after the first dose of entrectinib
    Evaluaciones tumorales se llevarán a cabo en la selección, al final del ciclo 1 (Ciclo 2 Día 1 +/- 2 días), cada 8 semanas (+/- 7 días) a partir de entonces a pesar de los retrasos de tratamiento que resultan de la toxicidad, y al final de tratamiento (si han pasado más de 4 semanas desde la última evaluación de imágenes).
    Rango de beneficio clínico; 6 mese despues de la primera dosis de entrectinib
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open 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 Yes
    E.8.1.7.1Other trial design description
    Basket study of entrectinib for the treatment of patients with solid tumors
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned 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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA72
    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
    Belgium
    Denmark
    Finland
    France
    Germany
    Hong Kong
    Ireland
    Israel
    Italy
    Japan
    Korea, Republic of
    Netherlands
    Norway
    Poland
    Romania
    Singapore
    Spain
    Sweden
    Switzerland
    Taiwan
    Thailand
    United Kingdom
    United States
    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
    The end of trial in all participating countries will be defined as the time at which the secondary endpoint of OS has been met, if the study is not terminated beforehand per recommendation of DMC
    Si el estudio no finaliza por adelantado según la recomendación del CVD, el fin del ensayo se establecerá en todos los países participantes como el momento en que se cumpla el criterio de valoración secundario de SG.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months7
    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: 200
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 state14
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 115
    F.4.2.2In the whole clinical trial 300
    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)
    None
    Ninguno
    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 Decision2016-08-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-22
    P. End of Trial
    P.End of Trial StatusOngoing
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