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    The EU Clinical Trials Register currently displays   44235   clinical trials with a EudraCT protocol, of which   7336   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).

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    Summary
    EudraCT Number:2012-002957-42
    Sponsor's Protocol Code Number:EMR200592-001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-05-16
    Trial results View 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 number2012-002957-42
    A.3Full title of the trial
    A Randomized, Double-Blind, Phase III Study of the Efficacy and Safety of Gemcitabine in Combination With TH-302 Compared With Gemcitabine in Combination With Placebo in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
    Estudio de fase III aleatorizado y doble ciego para comparar la eficacia y seguridad de la combinación de gemcitabina y TH-302 con las de la combinación de gemcitabina y placebo en pacientes con adenocarcinoma de páncreas irresecable localmente avanzado o metastático que no hayan recibido tratamiento con anterioridad
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical Trial testing TH-302 in combination with gemcitabine versus gemcitabine in combination with placebo in previously untreated patients with pancreatic cancer
    Ensayo Clinico probando TH -302 en combinación con gemcitabina comparado con la combinación de gemcitabina y placebo en pacientes con cancer pancreático que no hayan recibido tratamiento con anterioridad.
    A.4.1Sponsor's protocol code numberEMR200592-001
    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 SponsorMerck KGaA
    B.1.3.4CountryGermany
    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 supportMerck KGaA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck KGaA
    B.5.2Functional name of contact pointCommunication Center
    B.5.3 Address:
    B.5.3.1Street AddressFrankfurter Straße 250
    B.5.3.2Town/ cityDarmstadt
    B.5.3.3Post code64293
    B.5.3.4CountryGermany
    B.5.4Telephone number+496151725200
    B.5.5Fax number+496151722000
    B.5.6E-mailservice@merck.de
    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 nameTH-302
    D.3.2Product code TH-302
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 918633-87-1
    D.3.9.2Current sponsor codeTH-302
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Locally advanced unresectable pancreatic adenocarcinoma
    Adenocarcinoma de páncreas irresecable localmente avanzado
    E.1.1.1Medical condition in easily understood language
    Advanced Pancreatic Cancer
    Cáncer Pancreático avanzado.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.0
    E.1.2Level LLT
    E.1.2Classification code 10033606
    E.1.2Term Pancreatic cancer non-resectable
    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
    The primary objective of the trial is to evaluate efficacy, as measured by overall survival (OS), of gemcitabine in combination with TH-302 compared to gemcitabine in combination with placebo in subjects with previously untreated locally advanced unresectable or metastatic pancreatic adenocarcinoma.
    El objetivo principal de este estudio es evaluar la eficacia, medida mediante la supervivencia global (SG) de la combinación de gemcitabina con TH-302 en comparación con la combinación de gemcitabina con placebo en pacientes con adenocarcinoma de páncreas irresecable localmente avanzado o metastático que no hayan recibido tratamiento con anterioridad.
    E.2.2Secondary objectives of the trial
    To assess efficacy with resepct to:
    - progression free survival (PFS), and
    - objective response (OR) and disease control.
    To assess patient reported outcomes (PROs) with respect to quality of life (QoL) measured with EORTC QLQ-C30 (Version 3) and EQ-5D-5L, and pain measured by a Numerical Rating Scale (NRS).
    To investigate levels of carbohydrate antigen 19-9 (CA19-9),
    To assess the safety and tolerability of gemcitabine in combination with TH-302 compared with gemcitabine in combination with placebo.
    Evaluar la eficacia con respecto a:
    - la supervivencia sin progresión (SSP), y
    - la respuesta objetiva (RO) y el control de la enfermedad.
    Evaluar los resultados comunicados por el paciente (RCP) con respecto a la calidad de vida (CdV) medida con los cuestionarios QLQ-C30 (versión 3) de la EORTC y EQ-5D-5L, y al dolor medido con una escala de valoración numérica (EVN).
    Investigar la concentración del antígeno carbohidrato 19-9 (CA19-9).
    Evaluar la seguridad y tolerabilidad de la combinación de gemcitabina y TH-302 en comparación con la combinación de gemcitabina y placebo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - At least 18 years of age.
    - Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven by
    histology or cytology and previously untreated with chemotherapy or systemic therapy
    - Measurable disease (at least one target lesion outside of previous radiation fields) or
    non-measurable disease by RECIST 1.1 criteria (see Appendix III).
    - Documentation of disease progression since any prior therapy.
    - Life expectancy of at least 3 months.
    - Acceptable liver function.
    - Acceptable renal function.
    - Acceptable hematologic status.
    - please see protocol for full list of inclusion criteria
    - Edad mínima de 18 años.
    -Adenocarcinoma ductal de páncreas irresecable localmente avanzado o metastático confirmado mediante estudio histológico o citológico, y no tratado con anterioridad con quimioterapia o un tratamiento sistémico.
    - Enfermedad medible (al menos una lesión objetivo fuera de los campos de radiación anteriores) o enfermedad no medible según los criterios RECIST 1.1 (v. el Anexo III).
    -Demostración de la progresión de la enfermedad desde la administración de cualquier tratamiento anterior.
    -Esperanza de vida mínima de 3 meses.
    - Función hepática aceptable
    - Función renal aceptable
    - Estado hematológico aceptable
    - Véase en protocolo, listado completo de criterios de inclusión.
    E.4Principal exclusion criteria
    1. New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction within 6 months prior to the date of randomization, unstable arrhythmia or symptomatic peripheral arterial vascular disease.
    2. Symptomatic ischemic heart disease.
    3. Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months).
    4. Previous malignancy other than pancreatic cancer in the last 5 years, except for adequately treated non-melanoma skin cancer or pre-invasive cancer of the cervix.
    5. Severe chronic obstructive or other pulmonary disease with hypoxemia
    6. Major surgery, other than diagnostic surgery, ?28 days prior to the date of randomization.
    Subject must have completely recovered from surgery.
    7. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
    8. Treatment of pancreatic cancer with radiation therapy or surgery ?28 days prior to the date of
    randomization.
    9. Prior therapy with a hypoxic cytotoxin.
    10. Subjects who participated in an investigational drug or device trial ?28 days prior to Day 1 of
    the first cycle.
    11. Known infection with HIV, or an active infection with hepatitis B or hepatitis C.
    12. Subjects who have exhibited allergic reactions to a structural compound similar to TH-302 or
    the drug product excipients or to gemcitabine or its excipients.
    13. Please see protocol for full list of exclusion criteria.
    1.Insuficiencia cardíaca congestiva de clase III o IV según la NYHA (New York Heart Association), infarto de miocardio en los 6 meses anteriores a la fecha de la aleatorización, arritmia inestable o arteriopatía vascular periférica sintomática.
    2.Cardiopatía isquémica sintomática.
    3.Metástasis cerebrales, leptomeníngeas o epidurales conocidas (a menos que hayan recibido tratamiento y estén bien controladas durante al menos 3 meses).
    4.Neoplasia maligna anterior, con excepción del cáncer de páncreas, en los últimos 5 años, salvo el cáncer de piel no melanómico o el carcinoma in situ del cuello uterino, debidamente tratados.
    5.Neumopatía obstructiva crónica grave u otras enfermedades pulmonares que cursen con hipoxemia.
    6.Operación quirúrgica mayor (excepto diagnóstica) ? 28 días antes de la fecha de la aleatorización. El paciente debe haberse recuperado por completo de la operación quirúrgica.
    7.Infección bacteriana, vírica o micótica activa y no controlada que requiera tratamiento sistémico.
    8.Tratamiento del cáncer de páncreas con radioterapia o cirugía ? 28 días anteriores a la fecha de la aleatorización.
    9.Tratamiento anterior con una citotoxina hipóxica.
    10.Pacientes que hayan participado en otro estudio clínico con algún fármaco o dispositivo en investigación ? 28 días antes del día 1 del primer ciclo.
    11.Infección por el VIH diagnosticada o infección activa por el virus de la hepatitis B o C.
    12.Pacientes que hayan presentado reacciones alérgicas a un compuesto estructural parecido a TH-302 o a los excipientes del fármaco en estudio, o a la gemcitabina o sus excipientes.
    13. Véase protocolo para listado completo de criterios de exclusión.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is Overall Survival (OS) time.
    El criterio de valoración principal es el tiempo de Supervivencia Global (SG).
    E.5.1.1Timepoint(s) of evaluation of this end point
    OS will be evaluated when 508 events (deaths) of randomized patients are reported.
    La SG se evaluará cuando se hayan comunicado 508 episodios (muertes) de pacientes aleatorizados.
    E.5.2Secondary end point(s)
    - Progression-freee Survival (PFS) Time.
    - Best Overall Respose Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
    - Disease control Rate according to Response Evaluation Criteria in solid Tumors (RECIST) version 1.1.
    - Quality of Life (QOL) EuroQuol-5D (EG-5D) Health Outcome questionnaire.
    - Pain intensitiy using a visual analogue scale (VAS).
    - Serum CA 19-9 response rate.
    - Number of participants with treatment-emergent adverse events (TEAE) graded according to National Cancer Institute Common Terminology Criteria for Adverse Eents (NCI CTCAE v.4.03).
    ? Tiempo de supervivencia sin progresión
    ? Mejor tasa de respuesta global, según RECIST 1.1.
    ? Tasa de control de la enfermedad según (RECIST) version 1.1.
    ? Cuestionario de salud: EQ-5D-5L, cuestionario Calidad de Vida QLQ-C30,
    ? Escala de valoración numérica (EVN) de la intensidad del dolor
    ? Nivel de respuesta, serum CA19-9
    ? Numero de participantes con acontecimientos adversos aparecidos durante el tratamiento (AAAT) en términos clasificados y graduados conforme a los Criterios de terminología comunes para acontecimientos adversos del National Cancer Institute (CTCAE del NCI, v. 4.03)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary endpoints will be evaluated at the same timepoint as OS data is mature.
    Los criterios de valoración secundarios se evaluarán al mismo tiempo que los datos de supervivencia global estén disponibles-
    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 Yes
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Gemcitabine
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA125
    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
    European Union
    Austria
    Belgium
    Bulgaria
    Canada
    Czech Republic
    Finland
    France
    Germany
    Hungary
    Ireland
    Israel
    Italy
    Netherlands
    New Zealand
    Poland
    Romania
    Russian Federation
    Slovakia
    South Africa
    Spain
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Once the event-driven unblinding and final analysis is complete (unblinding and final analysis occurs after 508 events [deaths]), the Sponsor will initiate activities towards execution of an extension protocol, if appropriate, based on study outcomes, so that this Phase III study can be closed.
    Una vez terminados el proceso de desenmascaramiento motivado por algún episodio y el análisis final (el desenmascaramiento y el análisis final tendrán lugar después de que se produzcan 508 episodios [fallecimientos]), el promotor iniciará las actividades pertinentes destinadas a ejecutar un protocolo de ampliación, si procede, según los resultados del estudio, de manera que pueda cerrarse este estudio de fase III.
    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 months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    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: 260
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 400
    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 state70
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 400
    F.4.2.2In the whole clinical trial 660
    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)
    After a subject has completed the trial or has withdrawn early, usual treatment will be administered, if required, in accordance with the trial site?s standard of care and generally accepted medical practice and depending on the subject?s individual medical needs.
    Una vez el paciente haya completa el ensayo o se haya retirado prematuramente, recibirá el tratamiento usual, si lo requiere, de acuerdo con el procedimiento normalizado del centro y la práctica médica habitual, dependiendo de las necesidades específicas del paciente.
    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 Decision2013-06-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-05-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-05-04
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