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    Summary
    EudraCT Number:2014-002001-37
    Sponsor's Protocol Code Number:009684QM
    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:2015-05-08
    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 number2014-002001-37
    A.3Full title of the trial
    Phase II window of opportunity study of short term preoperative treatment with enzalutamide (alone or in combination with exemestane) in patients with primary breast cancer.
    Estudio de fase II de ventana de oportunidad, para evaluar el tratamiento preoperatorio a corto plazo con enzalutamida (en monoterapia o en combinación con exemestano) en pacientes con cáncer de mama primario (ARB).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A window of opportunity study of enzalutamide (alone or in combination with exemestane) in patients with newly diagnosed breast cancer who are awaiting surgery for their cancer.
    Estudio de Enzalutamida de ventana de oportunidad (solo o en combinación con exemestano) en pacientes con cáncer de mama recién diagnosticado que están en espera de la cirugía para su cáncer.
    A.3.2Name or abbreviated title of the trial where available
    ARB v1.0
    ARB v1.0
    A.4.1Sponsor's protocol code number009684QM
    A.5.4Other Identifiers
    Name:Not applicableNumber:Not applicable
    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 SponsorQueen Mary University London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstellas Pharma Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma Europe Ltd
    B.5.2Functional name of contact pointSuzanne Day
    B.5.3 Address:
    B.5.3.1Street Address2000 Hillswood Drive,
    B.5.3.2Town/ cityChertsey
    B.5.3.3Post codeKT16 0RS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number----
    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 Yes
    D.2.1.1.1Trade name Xtandi
    D.2.1.1.2Name of the Marketing Authorisation holderAstella Pharma Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameEnzalutamide
    D.3.2Product code MDV3100
    D.3.4Pharmaceutical form Capsule, soft
    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 INNEnzalutamide
    D.3.9.1CAS number 915087-33-1
    D.3.9.2Current sponsor codeEnzalutamide
    D.3.9.3Other descriptive nameMDV3100, MDV-3100, MDV 3100
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Exemestan cell pharm 25mg
    D.2.1.1.2Name of the Marketing Authorisation holdercell pharm GmbH | Theodor-Heuss-Str. 52 | 61118 Bad Vilbel | Germany
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameExemestane
    D.3.2Product code Not applicable
    D.3.4Pharmaceutical form Tablet
    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 INNExemestane
    D.3.9.1CAS number 107868-30-4
    D.3.9.2Current sponsor codeExemestane
    D.3.9.3Other descriptive nameN/A
    D.3.9.4EV Substance CodeAS4
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNExemestane
    D.3.9.1CAS number 107868-30-4
    D.3.9.2Current sponsor code107868-30-4
    D.3.9.3Other descriptive nameN/A
    D.3.9.4EV Substance CodeAS5
    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.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
    Primary breast cancer
    Cáncer de mama primario
    E.1.1.1Medical condition in easily understood language
    Newly diagnosed breast cancer
    Cáncer de mama recién diagnosticado
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10057654
    E.1.2Term Breast cancer female
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Determine the ability of enzalutamide, when taken alone or in combination with exemestane, to affect the growth of cancer cells in patients with newly diagnosed breast cancer.
    Determinar los efectos de la Enzalutamida (en monoterapia o en combinación con Exemestano) sobre la proliferación de las células tumorales.
    E.2.2Secondary objectives of the trial
    - Determine the effect of enzalutamide, when taken alone or in combination with exemestane, on tumour cell death.

    - Establish the safety and tolerability of enzalutamide, when taken alone or in combination with exemestane, in this patient population.

    - Evaluate changes in circulating hormone levels after enzalutamide administration
    ?Determinar los efectos de la Enzalutamida (en monoterapia o en combinación con Exemestano) sobre la apóptosis de las células tumorales.
    ?Determinar la seguridad y tolerabilidad de la Enzalutamida en monoterapia y en combinación con Exemestano en esta población.
    ?Evaluar los cambios en los niveles de hormonas circulantes tras la administración de Enzalutamida.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent prior to admission to this study
    2. Female, aged ?18 years
    3. ECOG performance status 0- 2
    4. Histologically confirmed invasive primary breast cancer
    5. Palpable breast tumour of any size, or tumour with an ultrasound or MRI size of at least 1.0 cm
    6. Haematologic and biochemical indices within the ranges shown below at the screening visit
    a) ANC ? 1500 cells/?l
    b) Platelet count ? 100000/?l
    c) Serum creatinine concentration < 1.5 x ULN
    d) Bilirubin level < 1.5 x ULN
    e) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 x ULN

    Inclusion Criteria unique to the ER+ve cohort
    1. ER+ve tumours defined as ?1% of tumour cells positive for ER on IHC staining or an IHC score (Allred) of ?3
    2. Postmenopausal defined as:
    a) Age ?55 years and 1 year or more of amenorrhea
    b) Age <55 years and 1 year or more of amenorrhea with LH and/or FSH levels in the postmenopausal range
    c) Age <55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range
    d) Status after bilateral oophorectomy (? 28 days prior to first study treatment)

    Inclusion Criteria unique to the AR+ve, TNBC cohort
    1. AR positive tumours defined as any nuclear AR staining by IHC (enrolment may be based on local pathology findings; subsequent review of AR expression by central pathology laboratory will be carried out)
    2. Triple-negative tumours, i.e. tumour cells are negative for
    a) ER with <1% of cells positive on IHC or an IHC score (Allred) of ?2
    b) PR with <1% of tumour cells positive on IHC or an Allred score of ?2
    c) HER2 with 0, 1+ or 2+ intensity on IHC and no evidence of amplification of the HER2 gene on ISH
    3. Negative serum or urine pregnancy test for women of childbearing potential within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible. Patients of childbearing potential must agree to use adequate contraception (for example, intrauterine device [IUD], birth control pills unless clinically contraindicated, or barrier device) beginning 2 weeks before the first dose of investigational medicinal product (IMP) and for 30 days after the final dose of IMP.
    1.Firma de consentimiento informado previa a la admisión en este estudio.
    2.Mujer, con una edad de ?18 años.
    3.Estado funcional ECOG 0-2.
    4.Cáncer de mama primario invasivo con confirmación histológica
    5.Tumor de mama palpable de cualquier tamaño, o tumor con un tamaño identificado por ecografía o resonancia magnética de al menos 1.0 cm.
    6.Índices hematológicos y bioquímicos dentro de los rangos a continuación descritos, evaluados durante la consulta de cribado.
    a.ANC ? 1500 células/µl
    b.Cuantificación de plaquetas ?100000/µl
    c.Concentración sérica de creatinina < 1.5 x LSN
    d.Nivel de bilirrubina < 1.5 x LSN
    e.Aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) <3 x LSN

    Criterios de inclusión únicos para la cohorte de ER+ve
    1.Los tumores ER+ve, definidos como que ?1% de las células tumorales son ER positivas según tinción inmunohistoquímica, o reciben una puntuación IHC (Allred) de ?3
    2.Estado posmenopáusico, definido como:
    a.Edad de ?55 años y 1 año o más de amenorrea.
    b.Edad de <55 años y 1 año o más de amenorrea con LH y/o niveles de FSH en el rango posmenopáusico.
    c.Edad de <55 años con histerectomía previa pero con los ovarios intactos con LH y/o niveles de FSH en el rango posmenopáusico.
    d.Estado tras ooforectomía bilateral (? 28 días antes del primer tratamiento en estudio.)

    Criterios de inclusión únicos para la cohorte de TNBC, ER+ve
    1.Los tumores AR positivos, definidos como toda tinción nuclear de AR mediante inmunohistoquímica (la inclusión se basará en hallazgos patológicos locales; el laboratorio patológico central realizará posteriormente una revisión de la expresión de AR).
    2.Tumores triple negativos, esto es, las células tumorales son negativas en
    a.ER con <1% de células positivas por inmunohistoquímica o una puntuación inmunohistoquímica (Allred) de ?2.
    b.PR con <1% de células positivas por inmunohistoquímica o una puntuación Allred de ?2.
    c.HER2 con una intensidad de 0, 1+ o 2+ por inmunohistoquímica y sin muestras de amplificación del gen HER2 por inmunohistoquímica.
    3.Test de embarazo negativo con suero u orina para las mujeres en edad reproductiva en las dos semanas anteriores a la primera dosis del tratamiento en estudio, preferiblemente lo más cerca posible de la administración de la primera dosis. Las pacientes en edad reproductiva deben dar acceder a emplear los métodos anticonceptivos adecuados (por ejemplo, DIU, píldoras anticonceptivas, a menos que esté clínicamente contraindicado, o algún método de barrera), iniciándolo en las dos semanas anteriores a la administración de la primera dosis del fármaco experimental y durante los 30 días posteriores a la última dosis del fármaco experimental.
    E.4Principal exclusion criteria
    1. Inflammatory breast cancer
    2. Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken:
    a) Oestrogens, including hormone replacement therapy;
    b) Androgens (testosterone, dihydroepiandrosterone, etc.);
    c) Any approved or investigational agent that blocks androgen synthesis or targets the AR (e.g., abiraterone acetate, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700)
    3. Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments); prior treatment for previous breast cancer or other neoplasms is allowed as long as it was completed at least 1 year prior to inclusion into this trial.
    4. History of seizure or any condition that may predispose to seizure; history of loss of consciousness or transient ischemic attack within 12 months before day 1.
    5. Significant cardiovascular disease, such as
    a) History of myocardial infarction, acute coronary syndromes or coronary angioplasty/stenting/bypass grafting within the past 6 months.
    b) Congestive heart failure New York Heart Association (NYHA) Class III or IV or history of congestive heart failure NYHA class III or IV, unless an echocardiogram or multigated acquisition scan performed within 3 months before day 1 reveals a left ventricular ejection fraction ? 45%;
    c) History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsade de pointes);
    6. Hypersensitivity to the active pharmaceutical ingredient or any of the excipients of the IMPs, including Labrasol, butylated hydroxyanisole, and butylated Hydroxytoluene
    7. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator?s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an IMP, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
    8. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
    9. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug ?30 days prior to study entry depending on the half-life of the investigational drug and/or guidance issued by the ARB IMP manufacturer. Please contact the ARB Coordinating team for further information.
    1.Cáncer de mama inflamatorio.
    2.Tratamiento con cualquiera de las siguientes medicaciones en las cuatro semanas anteriores a la toma de la biopsia diagnóstica:
    a.Estrógenos, incluyendo terapia hormonal sustitutiva;
    b.Andrógenos (testosterona, dihidroepiandrosterona, etc);
    c.Cualquier agente aprobado o experimental que bloquee la síntesis de andrógenos o afecte al AR (como el acetato de abiraterona, ARN-509, bicalutamida, enzalutamida, ODM-201, TAK-448, TAK-683, TAK-700).
    3.Tratamiento sistémico o local previo para el nuevo cáncer de mama primario actualmente en investigación (incluyendo cirugía, radioterapia, tratamientos citotóxicos y endocrinos); se permite haber recibido tratamiento previo para tratar un cáncer de mama u otra neoplasia anterior, siempre que éste haya concluido al menos un año antes de la inclusión en el estudio.
    4.Antecedentes de convulsiones o cualquier patología que pueda predisponer a la pacientes a sufrir convulsiones; antecedentes de pérdida de conocimiento o ataque isquémico transitorio en los 12 meses anteriores al día 1.
    5.Enfermedad cardiovascular relevante, como:
    a.Antecedentes de infarto de miocardio, síndromes coronarios agudos o angioplastia coronaria o colocación de stent o bypass en los últimos 6 meses.
    b.Insuficiencia cardíaca congestiva Clase III o IV según criterios de la New York Heart Association (NYHA) o antecedentes de haber sufrido una insuficiencia cardíaca de clase III o IV según NYHA, a menos que se haya realizado un ecocardiograma o una a ventriculografía isotópica (MUGA) en los tres meses anteriores al día 1 que hayan revelado una fracción de eyección de ? 45%;
    c.Antecedentes de haber sufrido arritmias ventriculares clínicamente significativas (por ej. taquicardia ventricular, fibrilación ventricular o torsade de pointes).
    6.Hipersensibilidad al principio activo farmacéutico o a alguno de los excipientes del fármaco experimental, incluyendo el Labrasol, el butilhidroxianisol y el Butilhidroxitolueno.
    7.Cualquier otra enfermedad, disfunción metabólica, hallazgo en examen físico o hallazgo clínico en laboratorio que, a criterio del investigador, indique sospecha de una enfermedad o patología para la que el uso del fármaco experimental esté contraindicado y que pueda afectar a la interpretación de los resultados y pongan en riesgo a la pacientes de sufrir complicaciones o interfiera con la firma del consentimiento informado.
    8.Impedimentos psicológicos, familiares, sociológicos o geográficos que imposibiliten el cumplimiento del protocolo del estudio.
    9.Tratamiento concomitante con otros fármacos experimentales o participación en otro ensayo clínico con cualquier otro fármaco en los ?30 días anteriores a la inclusión en el estudio, dependiendo del periodo de semidesintegración del fármaco experimental y/o las indicaciones del fabricante del fármaco experimental del estudio ARB. Para más información, por favor, contacte con el equipo de coordinación del estudio ARB.
    E.5 End points
    E.5.1Primary end point(s)
    ER positive cohort: The difference in geometric mean change (post treatment - pre treatment) in Ki67 expression between the two treatment arms.

    AR positive, triple negative breast cancer cohort: Individual anti-proliferative response (RR?Ki67), defined as a ?50% fall in Ki67 expression over the course of the study treatment.
    Cohorte positivo ER: La diferencia en el cambio medio geométrico (tratamiento post - tratamiento pre) en la expresión de Ki67 entre los dos brazos de tratamiento.

    AR positivo, Cohorte de cáncer de mama triple negativo: Respuesta individual anti-proliferativa (RR?Ki67), definido como una caída ?50% en la expresión de Ki67 en el transcurso del tratamiento de estudio.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint will be evaluated on breast cancer tumour samples collected prior to the start of study treatment and on completion of study treatment.
    El objetivo primario será evaluado en muestras tumorales de cáncer de mama recogidas antes del inicio del tratamiento del estudio y al término del tratamiento del estudio.
    E.5.2Secondary end point(s)
    1. Secondary Ki67 analyses:
    - Geometric mean change in Ki67 expression at the end of study treatment (Mean ?Ki67) (TNBC-cohort).
    - Geometric mean Ki67 expression at the end of study treatment (Mean Ki67post).
    - Individual end-of treatment anti-proliferative response (RRKi67-Post), defined as the natural logarithm of percentage positive Ki67 of less than 1 at the end of study treatment
    - Individual anti-proliferative response (RR?Ki67), defined as a ?50% fall in Ki67 expression over the course of the study treatment (ER+ve cohort.

    2. Changes in Caspase-3 IHC assessment between pre- and post-treatment tumour samples:
    - Geometric mean change in Caspase-3 between end-of-treatment and pre-treatment tumour samples (Mean ?Caspase-3).
    - Individual apoptotic response (RR?Caspase-3), defined as a ?50% increase in Caspase-3 over the course of the study treatment.

    3. Safety:
    - Incidence of serious adverse events (SAEs)
    - Incidence of grade 3 and 4 adverse events (AEs) (CTCAE, version 4.03)
    - Incidence of all AEs of all grades
    - Clinically significant changes in vital signs and clinical laboratory results during and following study drug administration

    4. Plasma levels of estrone, estrodiol, androstenedione, dihydroepiandrosterone, DHT, total/free testosterone, and sex-hormone binding globulin in blood samples taken prior to and after treatment.
    1. Análisis Secundarios de Ki67:
    - Cambio de la media geométrica en la expresión de Ki67 al final del tratamiento del estudio (?Ki67) (TNBC-cohorte).
    - Media geométrica de la expresión de Ki67 al final del tratamiento del estudio (Ki67post).
    - Respuesta anti-proliferativa individual al final de su tratamiento (RRKi67-Post), definido como el logaritmo natural del porcentaje positivo Ki67 de menos de 1 al final del tratamiento del estudio
    - Respuesta anti-prolifertaiva individual (RR?Ki67), definida como una caída ?50% en la expresión de Ki67 en el transcurso del tratamiento de estudio (ER + ve cohorte)

    2. Cambios en la evaluación de la caspasa-3 IHC entre muestras tumorales de tratamiento pre y post:
    - Cambio en la media geométrica en la caspasa-3 entre el final de su tratamiento y muestras de tumores pre-tratamiento (?Caspase-3).
    - Respuesta apoptótica Individual (RR?Caspase-3), definida como un aumento ?50% en la caspasa-3 en el transcurso del tratamiento de estudio.

    3. Seguridad:
    - Incidencia de acontecimientos adversos graves (EAG)
    - Incidencia eventos adversos de grado 3 y 4 (EA) (CTCAE, versión 4.03)
    - Incidencia de todos los acontecimientos adversos de todos los grados
    - Cambios clínicamente significativos en los signos vitales y los resultados de laboratorio clínicos durante y después de la administración del fármaco del estudio

    4. Los niveles plasmáticos de estrona, estrodiol, androstenediona, dihidroepiandrosterona, DHT, testosterona total / libre y globulina en muestras de sangre tomadas antes y después del tratamiento de unión a hormonas sexuales.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Secondary Ki67 analysis will be carried out on breast cancer tumour samples collected prior to the start of study treatment and on completion of study treatment.

    2. Changes in Caspase-3 will be investigated on breast cancer tumour samples collected prior to the start of study treatment and on completion of study treatment.

    3. Safety will be evaluated based on adverse events reported on the pre-treatment, post-treatment and safety visits.

    4. Circulating hormone levels will be measured on blood samples collected prior to the start of study treatment and on completion of study treatment.
    1. El ánálisis secundario Ki67 se llevará a cabo en muestras de tumores de cáncer de mama recogidas antes del comienzo del tratamiento del estudio y al término del tratamiento del estudio.

    2. Se estudiarán cambios en la caspasa-3 en muestras de tumores de cáncer de mama recogidas antes del inicio del tratamiento del estudio y al término del tratamiento del estudio.

    3. La seguridad se evalúa en función de los eventos adversos informados sobre las visitas de pre-tratamiento, post-tratamiento y seguridad.

    4. Se medirán los niveles de hormonas circulantes en muestras de sangre recogidas antes del comienzo del tratamiento del estudio y al término del tratamiento del estudio.
    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 No
    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 No
    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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA41
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    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
    The end of the trial is defined as 12 months after the last patient visit takes place in both cohorts.
    El final del ensayo se define como 12 meses después de la última visita del paciente que se lleve a cabo en ambas cohortes.
    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 months0
    E.8.9.1In the Member State concerned days31
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 235
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 235
    F.4.2.2In the whole clinical trial 235
    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, this is a window of opportunity trial. On completion of the study participating patients will either be considered for definitive surgery or primary medical treatment, e.g. neoadjuvant chemotherapy, at the discretion of the treating physician.
    Ninguno, este es un estudio de ventana de oportunidad. Al término del estudio los pacientes participantes, o bien son considerados para la cirugía definitiva o para tratamiento médico primario, por ejemplo, quimioterapia neoadyuvante, a discreción del médico tratante.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-06-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-05-07
    P. End of Trial
    P.End of Trial StatusCompleted
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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