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    Summary
    EudraCT Number:2015-001141-80
    Sponsor's Protocol Code Number:POLA/ACOG1401
    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:2015-08-13
    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 number2015-001141-80
    A.3Full title of the trial
    Phase Ib/II study to evaluate the efficacy and tolerability of PM01183 in combination with olaparib in patients with advanced solid tumors
    Estudio de Fase Ib/II para evaluar la eficacia y la tolerabilidad de PM01183 en combinación con olaparib en pacientes con tumores sólidos avanzados
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase Ib/II study to evaluate the efficacy and tolerability of PM01183 in combination with olaparib in patients with advanced solid tumors
    Estudio de Fase Ib/II para evaluar la eficacia y la tolerabilidad de PM01183 en combinación con olaparib en pacientes con tumores sólidos avanzados
    A.3.2Name or abbreviated title of the trial where available
    POLA
    POLA
    A.4.1Sponsor's protocol code numberPOLA/ACOG1401
    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 SponsorAndrés Poveda
    B.1.3.4CountrySpain
    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 supportAstra Zeneca
    B.4.2CountrySpain
    B.4.1Name of organisation providing supportPharma Mar
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAndrés Poveda
    B.5.2Functional name of contact pointAndrés Poveda
    B.5.3 Address:
    B.5.3.1Street AddressFundación Instituto Valenciano de Oncología (FIVO), Calle Profesor Baguena, 19
    B.5.3.2Town/ cityValencia
    B.5.3.3Post code46009
    B.5.3.4CountrySpain
    B.5.4Telephone number0034961104647
    B.5.6E-mailapoveda@fivo.org
    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 nameLurbinectedin
    D.3.2Product code PM01183
    D.3.4Pharmaceutical form Powder for 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 INNlurbinectedin
    D.3.9.1CAS number 497871-47-3
    D.3.9.2Current sponsor codePM01183
    D.3.9.3Other descriptive nameLURBINECTEDIN
    D.3.9.4EV Substance CodeSUB31196
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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 Yes
    D.2.1.1.1Trade name Lynparza
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
    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 nameOlaparib
    D.3.2Product code AZD2281
    D.3.4Pharmaceutical form Film-coated 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 INNOlaparib
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeAZD2281
    D.3.9.4EV Substance CodeSUB32234
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced or metastatic solid tumors (Phase I)
    Patients with potential tumors with possibly sensitivity to PARP inhibitors according to histology, or patients with molecular features (Phase II)
    Tumores sólidos avanzados o metastásicos (Fase I)
    Pacientes con tumores potenciales con posible sensibilidad a los inhibidores de PARP en función de su histología o pacientes con ciertas características moleculares (Fase II)
    E.1.1.1Medical condition in easily understood language
    Advanced or metastatic solid tumors
    Any type of tumor with potential molecular features with expected sentivity to PARP inhibitor
    Tumores sólidos avanzados o metastásicos
    Cualquier tipo de tumores con determinado perfil molecular que les haga sensibles a un inhibidor PARP
    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
    Phase Ib: To establish the safety [dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase II doses (RP2D)], of orally administered olaparib in combination with PM01183 in patients with advanced or metastatic solid tumors without established standard therapeutic alternatives.
    Phase II: To assess the efficacy in terms of Tumor response rate according to RECIST v1.1 criteria of PM01183 in combination with olaparib in the selected populations.
    Fase Ib: Establecer la seguridad [toxicidad limitante de la dosis (TLD), dosis máxima tolerada (DMT) y dosis recomendada para la Fase II (DRF2)] de olaparib administrado por vía oral en combinación con PM01183 en pacientes con tumores sólidos avanzados o metastásicos carentes de alternativas terapéuticas estándar establecidas.
    Fase II: Evaluar la eficacia, en términos de tasa de respuesta del tumor, según los criterios RECIST v1.1, de PM01183 en combinación con olaparib en determinadas poblaciones de pacientes.
    E.2.2Secondary objectives of the trial
    Phase Ib:To explore the pharmacokinetics of PM01183 and olaparib when dosed when administered in combination.To determine the effects of the study treatment on the level of PARP activity and DNA damage in:peripheral blood mononuclear cells (PBMC).Circulating tumor cells (CTC).Tumor biopsy samples.To evaluate the preliminary antitumor activity (overall response rate) by RECIST of the combination in the exposed population.
    Phase II:Progression free survival.Overall Survival.Toxicity profile of the combination in patients enrolled in the study.To explore the possible correlation between the expression of certain biomarkers and the efficacy of this therapeutic approach.
    Translational study:Pharmacodynamic evaluation to assess the increasing activity in DNA damage of the combination of PM01183+Olaparib (double strand break).To demonstrate the predictive capacity and prognostic impact of some of the biomarkers under study.
    Fase Ib:Explorar la farmacocinética de PM01183 y olaparib en su administración en combinación.Determinar efectos del tratamiento del estudio sobre nivel de actividad de la PARP y sobre daño en el ADN:Células mononucleares de sangre periférica(CMSP).Células tumorales circulantes (CTC).Muestras de biopsia tumoral.Evaluar de forma preliminar,mediante criterios RECIST,la actividad antitumoral (tasa global de respuesta) de la combinación en la población tratada
    Fase II:Supervivencia libre de progresión.Supervivencia global.Perfil de toxicidad de la combinación en los pacientes participantes en el estudio.Explorar la posible relación entre la expresión de ciertos biomarcadores y la eficacia de esta estrategia terapéutica
    Estudio translacional:Evaluación farmacodinámica del potencial aumento de la actividad sobre el daño en el ADN con la combinación PM01183+olaparib(roturas de doble cadena).Demostración de la capacidad predictiva y del impacto pronóstico de ciertos biomarcadores en estudio
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients equal or above to 18 years of age, no upper age limit.

    2. Written informed consent obtained prior to any study specific procedures or assessments.
    3. Histologically confirmed diagnosis of cancer:

    a. Phase I: patients with advanced or metastatic solid tumors without established standard therapeutic alternatives.
    b. Phase II: platinum-resistant ovarian cancer patients, triple negative breast cancer or patients with molecular features such as endometrial cancer with PTEN loss and breast or ovarian cancer with PTEN loss or known BRCA germline or somatic mutation or somatic methylation, and patients with high grade endometrial cancer.
    4. For patients included in the phase II part of the study, evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 is required.
    a. At least one lesion, not previously irradiated, that can be accurately measured at baseline as equal or above to 10 mm in the longest diameter (except lymph nodes which must have short axis equal or above to 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements,
    OR
    b. At least one lesion (measurable and/or non-measurable) that can be accurately assessed by (CT/MRI/plain x-ray) at baseline and follow up visits
    5. Patients included in the phase II part of the study must have received at least one line of standard therapy for locally advanced or metastatic disease, and developed progression disease afterwards.
    6. ECOG score less to 2.
    7. Life expectancy of above 3 months.
    8. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment evaluating:
    a. Haemoglobin
    b. Absolute neutrophil count
    No features suggestive of myelodisplastic syndrome (MSD)/ Acute myeloid leukaemia (AML) on peripheral blood smear
    c. White blood cells
    d. Platelet count
    e. Total bilirubin
    f. AST (SGOT)/ALT (SGPT)
    g. Albúmina
    h Serum creatinine
    i. Aclaramiento creatinina

    9. Patients should sign an informed consent form before inclusion in the study that
    specifies that the clinical trial treatment entails consent for the analysis of
    biological samples of tumor and blood.
    10. Patient is willing and able to comply with the protocol for the duration of the study
    including undergoing treatment and scheduled visits and examinations including follow
    up.
    11. Evidence of non-childbearing status for women of childbearing potential
    should only be included after a confirmed menstrual period and a negative
    urine or serum pregnancy test within 28 days of study treatment, confirmed prior to
    treatment on day 1. The inclusion of WOCBP requires use of a highly effective
    contraceptive measure
    1. Pacientes de 18 o más años de edad, sin límite superior de edad.

    2. Obtención del consentimiento informado por escrito antes que cualquiera de los procedimientos o evaluaciones del estudio.
    3. Diagnóstico de cáncer confirmado histológicamente:

    a. Fase I: pacientes con tumores sólidos avanzados o metastásicos sin alternativas terapéuticas estándar establecidas.
    b. Fase II: pacientes con cáncer de ovario resistente al platino, cáncer de mama triple negativo o pacientes con ciertas características moleculares, como cáncer de endometrio con supresión de la función de PTEN y cáncer de mama u ovario con supresión de la función de PTEN o mutación conocida de la estirpe germinal de BRCA o mutación somática o metilación somática, y pacientes con cáncer de endometrio de alto grado.
    4. En los pacientes incluidos en la parte de Fase II del estudio, se requiere evidencia de enfermedad medible según los Response Evaluation Criteria in Solid Tumors (RECIST), versión 1.1.
    a. Como mínimo una lesión, no radiada previamente, que pueda medirse con exactitud en el momento basal como mayor o igual a 10 mm en su eje mayor (excepto los ganglios linfáticos, cuyo eje menor debe ser mayor o igual a 15 mm) mediante tomografía computarizada (TAC) o resonancia magnética (RM) y susceptible de mediciones repetidas con exactitud,
    O BIEN
    b. Como mínimo una lesión (medible y/o no medible) que pueda evaluarse con precisión (TAC/RM/radiografía simple) en el momento basal y en las visitas de seguimiento.
    5. Los pacientes incluidos en la parte de Fase II del estudio deben haber recibido como mínimo una línea de tratamiento estándar por enfermedad localmente avanzada o metastásica y haber mostrado posteriormente progresión de la enfermedad.
    6. Puntuación del ECOG < 2.

    7. Esperanza de vida mayor o igual a 3 meses.

    8. Funciones orgánica y de médula ósea normales en su evaluación dentro de los 28 días previos a la administración del tratamiento del estudio, midiendo:
    a. Hemoglobina
    b. Recuento absoluto de neutrófilos
    Ausencia de características sugerentes de síndrome mielodisplásico (SMD)/leucemia mieloide aguda (LMA) en el frotis de sangre periférica
    c. Recuento de leucocitos
    d. Recuento de plaquetas
    e. Bilirrubina total
    f. AST (SGOT)/ALT (SGPT)
    g. Albumina
    h . Creatinina sérica
    i. Aclaramiento de creatinina

    9.Los pacientes deberán firmar un documento de consentimiento informado antes de su entrada en el estudio, en el que se especifique que el tratamiento del ensayo clínico supone su consentimiento para el análisis de muestras biológicas de tumor y sangre.
    10. Conformidad en y capacidad de cumplir con el protocolo a lo largo del estudio, lo que incluye recibir el tratamiento y someterse a las visitas y exámenes programados, así como al seguimiento.
    11 Evidencia de no embarazo. Las mujeres potencialmente fértiles sólo se pueden incluir tras confirmación de existencia de periodo menstrual y test negativo de embarazo en sangre o orina en los 28 días previos al inicio de tratamiento en el estudio , confirmado previa all tratamiento el dia 1. Se requiere el uso de métodos anticonceptivos altamente eficaces.
    E.4Principal exclusion criteria
    1. Involvement in the planning and/or conduct of the study.
    2. Previous enrolment or randomization in the present study.
    3. Simultaneous participation in any other study involving an investigational medicinal product, or having participated in a study less than 28 days prior to the start of study treatment.
    4. Any previous treatment with a PARP inhibitor, including olaparib, or PM01183.
    5. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
    6. Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. Concomitant use of known CYP3A4 inducers.
    7. Persistent toxicities (? CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
    8. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
    9. Blood transfusions within 1 month prior to study start.
    10. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
    11. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
    12. Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery.
    13. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan or any psychiatric disorder that prohibits obtaining informed consent.
    14. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
    15. Breast feeding women.
    16. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
    17. Patients with known active hepatic disease (i.e., Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
    18. Patients who present any contraindication or suspected allergy to the products (or any of the excipients) under investigation in the study.
    19. Patients with uncontrolled seizures.
    20. For patients included at the phase II part of the study: patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ? 5 years.
    1. Participación en la planificación y/o desarrollo del estudio.
    2. Reclutamiento o aleatorización anteriores en el presente estudio.
    3. Participación simultánea en cualquier otro estudio con un medicamento en investigación, o participación en otro estudio menos de 28 días antes del comienzo del tratamiento del presente estudio.
    4. Cualquier tratamiento previo con un inhibidor de PARP, incluido el olaparib, o con PM01183.
    5. Recepción de cualquier quimioterapia sistémica o radioterapia (excepto por razones paliativas) en el plazo de 2 semanas después de la última dosis del tratamiento del estudio (o un periodo mayor, dependiendo de las características de los agentes empleados). El paciente podrá recibir una dosis estable de bisfosfonatos por metástasis óseas, tanto antes como durante el estudio, a condición de que este producto se hubiera comenzado como mínimo 4 semanas antes del tratamiento con el fármaco del estudio.
    6. Administración concomitante de inhibidores conocidos de CYP3A4, como ketokonazol, itraconazol, ritonavir, indinavir, saquinavir, telitromicina, claritromicina y nelfinavir. Administración concomitante de inductores conocidos de CYP3A4.
    7. Acontecimientos adversos persistentes (? grado 2 de los CTCAE), con la excepción de alopecia, producidos por el tratamiento antineoplásico previo.
    8. ECG en reposo con QTc > 470 mseg en 2 o más momentos en un período de 24 horas, o historia familiar de síndrome de QT largo.
    9. Transfusiones de sangre en el plazo de 1 mes antes del comienzo del estudio.
    10. Pacientes con síndrome mielodisplásico/leucemia mieloide aguda.
    11. Pacientes con metástasis cerebrales sintomáticas no controladas. No se precisa un estudio computerizado para confirmar la ausencia de metástasis cerebrales. El paciente podrá recibir una dosis estable de corticosteroides antes y durante el estudio, siempre que haya comenzado con ese medicamento como mínimo 28 días antes del tratamiento del estudio.
    12. Cirugía mayor en el plazo de los 14 días previos al comienzo con el tratamiento del estudio; el paciente deberá haberse recuperado también de los efectos de toda cirugía mayor.
    13. Pacientes considerados como de alto riesgo médico por un proceso médico grave no controlado, enfermedad sistémica no maligna o infección activa no controlada. Entre otros ejemplos pueden señalarse los siguientes: arritmia ventricular no controlada, infarto de miocardio reciente (en los 3 meses últimos), compresión medular inestable (no tratada e inestable en los como mínimo 28 días antes de la entrada en el estudio), síndrome de vena cava superior, enfermedad pulmonar bilateral extensa en el TAC de alta resolución o cualquier trastorno psiquiátrico que prohíba la obtención del consentimiento informado.
    14. Pacientes incapaces de deglutir la medicación oral y pacientes con trastornos gastrointestinales que pudieran interferir con la absorción de la medicación del estudio.
    15. Mujeres en período de lactancia natural.
    16. Pacientes inmunocomprometidos, por ejemplo, pacientes que se sabe que son serológicamente positivos para el virus de la inmunodeficiencia humana (VIH) y en tratamiento con antivirales.
    17. Pacientes con enfermedad hepática activa conocida (hepatitis B o C) debido al riesgo de transmisión de la enfermedad a través de la sangre u otros fluidos orgánicos.
    18. Pacientes con cualquier contraindicación o sospecha de alergia a los productos (o sus excipientes) en investigación en el estudio.
    19. Pacientes con crisis convulsivas no controladas.
    20. Pacientes a incluir en la parte de Fase II del estudio: pacientes con un segundo cáncer primario, excepto el cáncer cutáneo de tipo no melanoma tratado adecuadamente, el cáncer in situ de cuello uterino tratado curativamente, u otros tumores sólidos tratados curativamente y sin evidencia de enfermedad desde hace ? 5 años.
    E.5 End points
    E.5.1Primary end point(s)
    Phase I: Safety (DLT, MTD and RP2D)
    Phase II: overall response rate (ORR)
    Fase Ib: seguridad (TLD, DMT y DRF2).
    Fase II: tasa global de respuesta (TGR).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Phase I: 6-9 months
    Phase II: 37 months
    Fase I: 6-9 meses
    Fase II: 37 meses
    E.5.2Secondary end point(s)
    ? Progression free survival (PFS).
    ? Overall survival (OS).
    ? To characterize the PK of this combination and to detect major drug-drug PK interactions
    ? To characterize pharmacodynamics profiles.
    ? Safety profile.
    ? Additional translational research.
    CRITERIOS SECUNDARIOS DE VALORACIÓN

    ? Supervivencia libre de progresión (SLP).
    ? Supervivencia global (SG).
    ? Caracterizar la farmacocinética de esta combinación y detectar las principales interacciones farmacocinéticas entre sus componentes
    ? Caracterizar los perfiles farmacodinámicos.
    ? Perfil de seguridad.
    ? Investigación translacional adicional.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Phase I: 6-9 months
    Phase II: 37 months
    Fase I: 6-9 meses
    Fase II: 37 meses
    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 Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Translational Research
    Estudio Translacional
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Translational Research
    Estudio Translacional
    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
    Un Fase I de escalada de dosis seguido de un Fase II no-randomizado, como estudio de expansión
    Phase I Dose escalation part followed by a non-randomized Phase II part, as an expansion study
    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.8.3 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 concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    Última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months10
    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: 114
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 7
    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 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 state121
    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 Decision2015-07-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-07-10
    P. End of Trial
    P.End of Trial StatusOngoing
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