Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39185   clinical trials with a EudraCT protocol, of which   6421   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).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2010-022656-22
    Sponsor's Protocol Code Number:A7471009
    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:2011-06-16
    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 number2010-022656-22
    A.3Full title of the trial
    A randomized double blind phase 3 efficacy and safety study of PF-00299804 versus erlotinib for the treatment of advanced non-small cell lung cancer following progression after, or intolerance to, at least one prior chemotherapy.
    Estudio en fase 3, aleatorizado y doble ciego para evaluar la eficacia y la seguridad de PF-00299804 frente a erlotinib en el tratamiento del cáncer pulmonar no microcítico avanzado tras la progresión durante al menos una quimioterapia previa o en caso de intolerancia.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomized, double blind, phase 3 study of PF-00299804 versus erlotinib in the treatment of advanced non-small cell lung cancer
    Estudio en fase 3, aleatorizado, doble ciego de PF-00299804 frente a erlotinib en el tratamiento del cáncer pulmonar no microcítico avanzado
    A.4.1Sponsor's protocol code numberA7471009
    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 SponsorPfizer, S.L.U.
    B.1.3.4CountrySpain
    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 supportPfizer Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc
    B.5.2Functional name of contact pointClinical Trials.gov Call Centre
    B.5.3 Address:
    B.5.3.1Street Address235 E 42 nd street
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 1007
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 800 7181021
    B.5.5Fax number+1303 7391119
    B.5.6E-mailClinicalTrials.govCallCentre@Pfizer.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.3.2Product code PF-00299804
    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 INNNA
    D.3.9.1CAS number 1042385-75-0
    D.3.9.2Current sponsor codePF-00299804
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code PF-00299804
    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 INNNA
    D.3.9.1CAS number 1042385-75-0
    D.3.9.2Current sponsor codePF-00299804
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP 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.3.2Product code PF-00299804
    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 INNNA
    D.3.9.1CAS number 1042385-75-0
    D.3.9.2Current sponsor codePF-00299804
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number45
    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: 4
    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 TARCEVA 25 mg comprimidos recubiertos con película
    D.2.1.1.2Name of the Marketing Authorisation holderROCHE REGISTRATION LIMITED
    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.3.4Pharmaceutical 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 INNERLOTINIB
    D.3.9.3Other descriptive nameERLOTINIB
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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: 5
    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 TARCEVA 100 mg comprimidos recubiertos con película
    D.2.1.1.2Name of the Marketing Authorisation holderROCHE REGISTRATION LIMITED
    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.3.4Pharmaceutical 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 INNERLOTINIB
    D.3.9.3Other descriptive nameERLOTINIB
    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.IMP: 6
    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 TARCEVA 150 mg comprimidos recubiertos con película
    D.2.1.1.2Name of the Marketing Authorisation holderROCHE REGISTRATION LIMITED
    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.3.4Pharmaceutical 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 INNERLOTINIB
    D.3.9.3Other descriptive nameERLOTINIB
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 4
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 5
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 6
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-small cell lung cancer
    Cancer de pulmon no microcitico
    E.1.1.1Medical condition in easily understood language
    PF-0299804 is for the potential treatment of patients with locally advanced or metastatic non-small cell lung cancer after failing of at least one prior chemotherapy regimen
    PF-0299804 es un posible tratamiento para pacientes con cancer de pulmon no microcitico avanzado o metastasico tras el fallo al menos un regimen previo de quimioterapia
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 13.1
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    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
    To demonstrate that PF 00299804 treatment is superior to erlotinib treatment with respect to Progression Free Survival (PFS) in either of the co primary populations.
    Demostrar que el tratamiento con PF 00299804 es superior al tratamiento con erlotinib con respecto a la supervivencia sin progresión (SSP) en cualquiera de las poblaciones principales.
    E.2.2Secondary objectives of the trial
    To compare secondary measures of Overall Survival (OS), Objective Response Rate and Duration of Response between arms in the co primary populations;
    To evaluate the safety and tolerability in each arm;
    To compare the Patient Reported Outcomes (PRO) of health related quality of life, and disease/treatment related symptoms between arms in the co primary populations, respectively;
    To compare Patient Reported Outcomes (PRO) of health status between arms in the co primary populations, respectively;
    To determine KRAS genotype, and explore HER family genotype, in tumor tissue;
    To determine PF 00299804 and PF 05199265, (O desmethyl metabolite of PF 00299804, a major circulating metabolite in human plasma) trough concentrations (Ctrough) for the evaluation of steady state pharmacokinetics;
    Comparar los criterios de valoración secundarios de supervivencia global (SG), respuesta objetiva TRO y duración de la respuesta entre los grupos en las poblaciones principales;
    Evaluar la seguridad y la tolerabilidad en cada grupo
    Comparar los resultados comunicados por el paciente (RCP) respecto a la calidad de vida relacionada con la salud y los síntomas relacionados con la enfermedad o con el tratamiento entre los grupos en las poblaciones principales, respectivamente;
    Comparar los resultados comunicados por el paciente (RCP) respecto al estado de salud entre los grupos en las poblaciones principales, respectivamente;
    Determinar el genotipo de KRAS e investigar el genotipo de la familia HER en muestras de tejido tumoral;
    Determinar las concentraciones mínimas (Cmín) de PF 00299804 y PF 05199265 (metabolito O-desmetilo de PF 00299804, uno de los principales metabolitos circulantes en plasma humano) para la evaluación de la farmacocinética en estado de equilibrio;
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Exploratory research samples for Pfizer's Biobank
    Muestras para el biobanco de investigación exploratoria de Pfizer
    E.3Principal inclusion criteria
    1.Provision of a voluntarily given, personally signed, and dated written informed consent document;
    2.Age >=18 years, male or female;
    3.Evidence of pathologically confirmed, advanced NSCLC for which there is no curative standard therapy;
    a.For the purpose of randomization/ stratification, the histologic subtype of NSCLC must be documented, preferably by WHO/ International Association for Study of Lung Cancer Histologic Classification of Lung Cancer criteria;
    b.The diagnosis of NSCLC NOS (not otherwise specified) will not be sufficient for enrollment and randomization/stratification.
    4.Specimen from archival or recently obtained tumor tissue is required, and will be sent to the Sponsor designated central laboratory for molecular testing of tumor tissue, including KRAS mutation status, and HER family testing (as available tissue allows).
    5.ECOG 0-2 performance status;
    6.Prior treatment with at least one and no more than two regimens of systemic therapy which include at least one standard chemotherapy for advanced NSCLC. For the purpose of this study the following convention regarding the counting of prior therapy regimen will be followed:
    •Prior systemic adjuvant therapy or combined modality chemoradiation for locally advanced disease will not be counted against the total of 1 or 2 allowed prior regimens for advanced NSCLC if treatment was completed more than 12 months prior to ramdomization.
    •Administration of a new agent upon completion of 4 6 cycles of platin based therapy but prior to documentation of progressive NSCLC is considered an additional regimen.
    •Discontinuation of any systemic anti cancer drug due to intolerance (without documentation of progression of NSCLC) following administration of at least one full dose will count as one regimen.
    •Substitution of one component of a combination drug regimen following administration of at least one full dose of the agent is considered the start of a new regimen (with the exception of substitution of the platin component of a cisplatin or carboplatin doublet).
    •Prior investigational therapy in combination with a standard chemotherapy for NSCLC is counted as one regimen of systemic therapy;
    7.Any prior treatment (chemotherapy, radiation or surgery) must have been completed at least 2 weeks prior to randomization. Any acute toxicity related to prior therapy must have been recovered to Grade 1 (per NCI CTCAE v4) or baseline;
    8.Radiologically measurable disease by RECIST v1.1 criteria:
    9.Brain metastases treated with radiation or surgery are allowed if radiologically and neurologically stable and the subject is off corticosteroids for at least 2 weeks prior to randomization;
    10.Adequate Renal Function, including:
    a.Estimated creatinine clearance >=15 mL/min (as determined by site’s standard formula);
    b.No known history of renal papillary necrosis or pyelonephritis.
    11.Adequate Liver Function, including:
    •Bilirubin <=1.5 x upper limit of normal (ULN);
    •AST (SGOT) <=2.5 x ULN (<=5.0 x ULN if hepatic metastases);
    •ALT (SGPT) <=2.5 x ULN (<=5.0 x ULN if hepatic metastases).
    12.Female patients or their partners must be surgically sterile or be postmenopausal (defined as 12 months of amenorrhea following last menses), or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter.
    13.All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 72 hours prior to starting treatment.
    14.Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter.
    15.Patients who are willing and able to comply with study scheduled visits, treatment plans, laboratory tests, and other study procedures including patient reported measures.
    1.Presentación de un documento de consentimiento informado por escrito, firmado y fechado personalmente, otorgado de forma voluntaria.
    2.Varones o mujeres de edad ≥ 18 años.
    3.Pruebas de CPNM avanzado confirmado por anatomía patológica para el que no existe ningún tratamiento estándar curativo;
    a.Para los fines de la aleatorización/estratificación, se documentará el subtipo histológico del CPNM, preferiblemente con los criterios de clasificación histológica del cáncer de pulmón de la OMS/Asociación Internacional para el Estudio del Cáncer de Pulmón;
    b.El diagnóstico de CPNM no especificado no será suficiente para realizar el reclutamiento y la aleatorización/estratificación.
    4.Se precisa una muestra de tejido tumoral de archivo u obtenida recientemente, y se enviará al laboratorio central designado por el promotor para realizar análisis moleculares del tejido tumoral, incluida la presencia de mutaciones de KRAS, Y análisis de la familia de HER.
    5.Estado funcional del ECOG de 0 a 2;
    6.Tratamiento previo con al menos una y no más de dos pautas de tratamiento sistémico, que incluyan al menos una quimioterapia convencional. Se aplicará la siguiente norma para el recuento de las pautas de tratamiento previas:
    •El tratamiento adyuvante sistémico o la radioquimioterapia combinada para la enfermedad localmente avanzada no se contabilizarán en el total de 1 ó 2 pautas previas permitidas para el CPNM avanzado si la administración concluyó más de 12 meses antes de la aleatorización.
    •La administración de un nuevo fármaco después de 4 a 6 ciclos de tratamiento basado en platino, pero antes de la documentación de CPNM progresivo, se considera un tratamiento adicional.
    •La retirada de cualquier fármaco antineoplásico sistémico por intolerancia (sin documentación de progresión del CPNM) tras la administración de al menos una dosis completa se contabilizará como una pauta.
    •La sustitución de un componente de una pauta de combinación tras la administración de al menos una dosis plena del fármaco se considera el inicio de una nueva pauta (con la excepción de la sustitución del componente platino de una combinación doble con cisplatino o carboplatino).
    •El tratamiento experimental previo en combinación con una quimioterapia estándar para el CPNM se contabiliza como una pauta de tratamiento sistémico;
    7.Todo tratamiento previo (quimioterapia, radioterapia o cirugía) deberá haberse finalizado al menos 2 semanas antes de la aleatorización. Toda toxicidad aguda relacionada con el tratamiento previo deberá haberse recuperado hasta un grado 1 (según los CTCAE del NCI v4) o la situación basal.
    8.Enfermedad mensurable por radiología según la v.1.1 de los criterios RECIST:
    9.Se permitirán las metástasis cerebrales tratadas con radiación o cirugía en caso de encontrarse radiológica y neurológicamente estables y si el paciente lleva sin corticoides al menos 2 semanas antes de la aleatorización.
    10.Función renal adecuada, lo que incluye:
    a.Aclaramiento de creatinina calculado ≥ 15 ml/min;
    b.Ausencia de antecedentes conocidos de necrosis papilar renal o pielonefritis.
    11.Función hepática adecuada, lo que incluye:
    •Bilirrubina ≤ 1,5 x límite superior de la normalidad (LSN);
    •AST (SGOT) ≤ 2,5 veces x LSN (≤5,0 veces x LSN en caso de metástasis hepáticas);
    •ALT (SGPT) ≤ 2,5 veces x LSN (≤5,0 veces x LSN en caso de metástasis hepáticas).
    12.Las mujeres (o sus parejas) deberán estar esterilizadas por métodos quirúrgicos o ser posmenopáusicas (definido como 12 meses de amenorrea tras la última menstruación), o deberán acceder a usar un método anticonceptivo eficaz mientras reciban el tratamiento del estudio y por lo menos 3 meses después.
    13.Todas las mujeres en edad fértil deberán dar negativo en una prueba de embarazo en las 72 horas anteriores al inicio del tratamiento.
    14.Los varones o sus parejas deberán estar esterilizados por métodos quirúrgicos o deberán acceder a usar un método anticonceptivo eficaz mientras reciban el tratamiento del estudio y por lo menos 3 meses después.
    15.Pacientes dispuestos a cumplir las visitas programadas, el plan de tratamiento, los análisis clínicos y otros procedimientos del estudio, incluidos los resultados comunicados por los pacientes, y capaces de hacerlo.
    E.4Principal exclusion criteria
    1.Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer.
    2.Patients with known leptomeningeal metastases, or symptomatic brain metastases. Patients with previously diagnosed brain metastases for which treatment (radiation or surgery) is recommended in the judgment of investigator are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable.
    3.Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 2 weeks of baseline disease assessments.
    4.Prior therapy with an agent that is known or proposed to be active by action on: EGFR tyrosine kinase or other HER family proteins including but not limited to erlotinib (Tarceva®), gefitinib (Iressa®), lapatinib (Tykerb®), cetuximab (Erbitux®), panitumumab (Vectibix®), trastuzumab (Herceptin®), ZD6474 (Zactima®), cantertinib (CI 1033), neratinib (HKI 272), Tovok (BIBW 2992), XL 647, AEE788, matuzumab, and pertuzumab.
    5.Investigational therapy as only treatment for advanced NSCLC, without administration of an approved chemotherapy for advanced NSCLC.
    6.Any surgery (not including minor procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
    7.Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication.
    8.Current enrollment in another therapeutic clinical trial.
    9.Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this study.
    10.Patients with known diffuse interstitial lung disease.
    11.Uncontrolled or significant cardiovascular disease, including:
    a.Myocardial infarction within 12 months;
    b.Uncontrolled angina within 6 months;
    c.Congestive heart failure within 6 months;
    d.Diagnosed or suspected congenital long QT syndrome;
    e.Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
    f.Prolonged QTc interval on pre entry electrocardiogram. QTc must be less than CTC Grade 2 (≤480 msec) using Fredricia’s correction formula with manual read by investigator if required. The ECG may be repeated for evaluation of eligibility after management of correctable causes for observed QTc prolongation;
    g.Any history of second or third degree heart block (may be eligible if currently have a pacemaker);
    h.Heart rate <50/minute on baseline electrocardiogram;
    i.Uncontrolled hypertension.
    12.Prior malignancy: Patients will not be eligible if they have evidence of other malignancy (other than non melanoma skin cancer or in situ cervical cancer, or localized and presumed cured prostate cancer with Prostate Specific Antigen (PSA) < ULN) within the last 3 years.
    13.Other severe acute or chronic medical condition that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
    14.Medications are prohibited at baseline and prior to randomization if they affect the pharmacokinetics of erlotinib or if they are mainly metablolized by CYP2D6. Patients who are otherwise eligible can be enrolled only if drug substitution is performed with acceptable clinical outcome prior to randomization. Prohibited medications are described below.
    15.Patients who are investigational site staff members or patients who are Pfizer employees directly involved in the conduct of the trial.
    No se incluirá en este ensayo clínico a los pacientes que presenten alguno de los siguientes criterios:
    1.Cualquier dato de histología mixta que incluya elementos de cáncer de pulmón microcítico o carcinoide.
    2.Pacientes con metástasis leptomeníngeas conocidas o metástasis cerebrales sintomáticas. Los pacientes con metástasis cerebrales diagnosticadas previamente para los que se recomienda tratamiento (radioterapia o cirugía) a criterio del investigador podrán participar en el estudio si han finalizado su tratamiento y se han recuperado de los efectos agudos de la radioterapia o cirugía antes del inicio de la medicación del estudio, han interrumpido el tratamiento con corticoides de estas metástasis durante al menos 2 semanas y se encuentran estables desde el punto de vista neurológico.
    3.Quimioterapia, radioterapia (aparte de la radioterapia paliativa sobre lesiones que no serán objeto de seguimiento en cuanto a evaluación del tumor durante este estudio, es decir, lesiones no diana), productos biológicos o fármacos en investigación durante las 2 semanas anteriores a las evaluaciones de la enfermedad basales.
    4.Tratamiento previo con un fármaco que se sabe o se ha propuesto que es activo debido a su efecto sobre: tirosina cinasa del EGFR u otras proteínas de la familia HER, entre ellas, a título de ejemplo, erlotinib (Tarceva®), gefitinib (Iressa®), lapatinib (Tykerb®), cetuximab (Erbitux®), panitumumab (Vectibix®), trastuzumab (Herceptin®), ZD6474 (Zactima®), cantertinib (CI-1033), neratinib (HKI-272), Tovok (BIBW-2992), XL-647, AEE788, matuzumab y pertuzumab.
    5.Tratamiento en investigación como único tratamiento del CPNM avanzado, sin administración de una quimioterapia aprobada para el CPNM avanzado.
    6.Toda intervención quirúrgica (salvo las intervenciones de cirugía menor como una biopsia de ganglios linfáticos) durante las 2 semanas anteriores a las evaluaciones de la enfermedad basales o ausencia de recuperación plena de los efectos secundarios de intervenciones previas.
    7.Toda anomalía digestiva con importancia clínica que pueda alterar la toma, el tránsito o la absorción del fármaco del estudio, como la incapacidad de tomar medicación oral.
    8.Tratamiento actual en otro ensayo clínico terapéutico.
    9.Todo trastorno psiquiátrico o cognitivo que limitaría la comprensión o la concesión del consentimiento informado y el cumplimiento de los requisitos de este estudio.
    10.Pacientes con neumopatía intersticial difusa conocida.
    11.Enfermedad cardiovascular no controlada o importante, lo que incluye:
    a.Infarto de miocardio durante los 12 meses anteriores.
    b.Angina de pecho no controlada durante los 6 meses anteriores.
    c.Insuficiencia cardíaca congestiva en los 6 meses previos;
    d.Síndrome de QT largo congénito diagnosticado o sospechado.
    e.Antecedentes de arritmias ventriculares con importancia clínica (como taquicardia ventricular, fibrilación ventricular o torsades de pointes).
    f.Intervalo QTc prolongado en el electrocardiograma previo a la entrada en el estudio. El QTc deberá ser menor de un grado 2 CTC ( 480 ms) utilizando la fórmula de corrección de Fridericia, con lectura manual por el investigador, si procede. El ECG podrá repetirse para evaluar la elegibilidad después de tratar las causas corregibles de una prolongación del QTc observada.
    g.Antecedentes de bloqueo cardíaco de segundo o tercer grado (podrá ser elegible en caso de tener implantado un marcapasos).
    h.Frecuencia cardíaca < 50/minuto en el electrocardiograma basal.
    i.Hipertensión arterial no controlada.
    12.Neoplasia maligna previa: los pacientes no serán elegibles en caso de tener indicios de otra neoplasia maligna (distinta de un cáncer de piel no melanomatoso, un cáncer de cuello uterino in situ o un cáncer de próstata localizado y supuestamente curado con un valor de antígeno prostático específico (PSA) < LSN) durante los últimos 3 años.
    13.Otro proceso médico grave, agudo o crónico, que pueda aumentar el riesgo asociado a la participación en el ensayo o a la administración del producto en investigación o interferir en la interpretación de los resultados del ensayo y que, en opinión del investigador, haría inadecuada la inclusión del sujeto en este ensayo.
    14.Se prohíbe la administración de medicamentos en el momento basal y antes de la aleatorización si afectan a la farmacocinética de erlotinib o si son metabolizados principalmente por la CYP2D6. Solo podrá reclutarse a los pacientes que, por lo demás, sean elegibles en caso de realizar una sustitución del fármaco con un resultado clínico aceptable antes de la aleatorización. Los medicamentos prohibidos se describen a continuación.
    15.Pacientes que sean miembros del personal del centro de investigación o empleados de Pfizer directamente implicados en la realización del ensayo.
    E.5 End points
    E.5.1Primary end point(s)
    Progression Free Survival (PFS) per Independent Radiologic Review in the co primary populations.
    Supervivencia sin progresion evaluada por revisor radiologico independiente en las poblaciones principales
    E.5.1.1Timepoint(s) of evaluation of this end point
    To demonstrate that PF 00299804 treatment is superior to erlotinib treatment with respect to Progression Free Survival (PFS) in either of the co primary populations
    Demostrar que el tratamiento con PF 00299804 es superior al tratamiento con erlotinib con respecto a la supervivencia sin progresión (SSP) en cualquiera de las poblaciones principales.
    E.5.2Secondary end point(s)
    • Overall Survival (OS);
    • Progression Free Survival (PFS) per investigator assessment;
    • Best Overall Response (BOR);
    • Duration of Response (DR).
    Overall safety profile as characterized by type, frequency, severity of adverse events as graded by NCI Common Toxicity Criteria for Adverse Events version 4 (NCI CTCAE.v4, Publish Date: 2010, http://ctep.cancer.gov/reporting/ctc.html), timing and relationship to treatment on each arm, laboratory abnormalities observed, and left ventricular imaging observed.
    Patient Reported Outcomes of health related quality of life, and disease/treatment related symptoms for patients in each arm as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30), Appendix 5, and its Lung Cancer module (QLQ LC13) Appendix 6.
    Patient Reported Outcomes of health status for patients in each arm as measured by the EuroQol 5 Dimension (EQ 5D) Appendix 7.
    KRAS and HER family genotypes in tumor tissue (fresh or archived);
    Trough concentrations (Ctrough) of PF 00299804 and PF 05199265, as determined from trough plasma samples;
    Pre and post treatment levels in serum of circulating extracellular domains (ECD) or shed receptors of the HER signaling pathways or protein/ligands which interact with or are part of HER signaling pathways or escape pathways (including, but possibly not limited to, EGFR and HER 2 receptor ECD, E cadherin, TGFalpha, EGF, amphiregulin, HGF), or proteins/peptides potentially predicting response or resistance to PF 00299804 or erlotinib;
    Optional Research Components:
    Subject to IRB/IEC approval/favorable opinion, this study will include an additional research component involving collection of biological samples (whole blood and plasma) at baseline for de identified exploratory molecular profiling (“ ‘omics”) analysis. The Molecular Profiling Supplement to this protocol provides a description of this additional research. Patients may participate in the study even if they choose not to participate in this sample banking component.
    Subject to IRB/IEC approval/favorable opinion, this study will include an additional optional research component involving the collection of tissue samples at progression for exploratory biomarker studies (eg, biopsy, or thoracentesis or paracentesis for preparation of a cell block). Tumor tissue would be obtained from patients agreeing to undergo sampling procedure and who in judgment of investigator have accessible tissue and are clinically stable within 4 weeks of progression. Patients, Investigators and/or Institutions may elect not to participate in this portion of the study.
    • Supervivencia global (SG).
    • Supervivencia sin progresión (SSP) según la evaluación del investigador.
    • Mejor respuesta global (MRG).
    • Duración de la respuesta (DR).
    Perfil de seguridad global determinado por el tipo, la frecuencia y la intensidad de los acontecimientos adversos, clasificados con los Criterios terminológicos comunes para acontecimientos adversos del NCI, versión 4 (CTCAE del NCI v4, fecha de publicación: 2010, http://ctep.cancer.gov/reporting/ctc.html), el momento de aparición y la relación con el tratamiento en cada grupo, las anomalías analíticas observadas y las imágenes del ventrículo izquierdo que se obtengan.
    Resultados comunicados por los pacientes de calidad de vida relacionada con la salud y síntomas relacionados con la enfermedad/tratamiento en los pacientes de cada grupo, según lo determinado mediante el Cuestionario de calidad de vida de la European Organization for Research and Treatment of Cancer (QLQ de la EORTC-C30), apéndice 5, y su módulo de cáncer de pulmón (QLQ-LC13), apéndice 6.
    Resultados comunicados por los pacientes respecto al estado de salud de los pacientes de cada grupo, según lo determinado por el cuestionario EuroQol de 5 dimensiones (EQ-5D) apéndice 7.
    Genotipos de KRAS y de la familia HER en tejido tumoral (reciente o archivado);
    Concentraciones mínimas (Cmín) de PF 00299804 y PF-05199265, a partir de muestras de plasma obtenidas al final del intervalo de administración;
    Concentración antes y después del tratamiento de los dominios extracelulares circulantes (DEC) o de los receptores diseminados en suero de las vías de transmisión de señales HER, o de las proteínas/ligandos que interactúan con las vías de escape y transmisión de señales HER o que forman parte de ellas (como, posiblemente entre otros, los DEC de EGFR y del receptor HER 2, E-cadherina, TGF-alfa, EGF, anfirregulina, HGF) o proteínas/péptidos capaces de predecir la respuesta o la resistencia a PF 00299804 o a erlotinib.
    Componentes de investigación opcionales:
    Este estudio constará de un componente de investigación adicional que requerirá la recogida de muestras biológicas (sangre completa y plasma) en el momento basal para análisis de determinación del perfil molecular exploratorios anónimos (“ómica”), siempre que el CEIC otorgue su aprobación o dictamen favorable. En el Suplemento de determinación del perfil molecular de este protocolo se describe esta investigación complementaria. Los pacientes podrán participar en este estudio aunque decidan no participar en este componente de conservación en bancos de muestras.
    Este estudio constará de un componente de investigación adicional que consistirá en la recogida de muestras de tejido en el momento de progresión para estudios exploratorios sobre biomarcadores (por ejemplo, biopsia, toracocentesis o paracentesis para la preparación de un bloque celular), siempre que el CEIC otorgue su aprobación o dictamen favorable. Se obtendrá tejido tumoral de los pacientes que acepten someterse al procedimiento de obtención de muestras y que, a juicio del investigador, presenten tejido accesible y estén clínicamente estables en las 4 semanas siguientes a la progresión. Los pacientes, los investigadores y los centros podrán optar por no participar en esta parte del estudio.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Overall Survival. Patients will be followed up until death (unless the patient is lost to follow-up)
    Supervivencia global. Los pacientes seran seguidos hasta fallecimiento (a menos que el pacientes sea una perdida de seguimiento)
    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 Yes
    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 No
    E.6.11Pharmacogenomic Yes
    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 Yes
    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 No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA78
    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
    Austria
    Belgium
    China
    Denmark
    Finland
    France
    Germany
    Greece
    Hong Kong
    Hungary
    India
    Ireland
    Japan
    Korea, Republic of
    Mexico
    Peru
    Poland
    Russian Federation
    Slovakia
    South Africa
    Spain
    Sweden
    Switzerland
    Turkey
    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
    As per protocol.
    Según indica el protocolo.
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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: 540
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 260
    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 state51
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 800
    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)
    This is a research study, the study drug, PF-00299804, & the study defined medical care will only be given to patients during the sudy, unless patients experience AEs which require appropriate follow-up.
    As stated in the protocol, for adverse events (serious/non-serious) with a causal relationship to the study drug, follow-up by the investigator is required until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, & Pfizer concurs with that assessment.
    PF00299804 será solo proporcionado durante el ensayo a menos que los pacientes experimenten AE los cuales requieran un seguimiento adecuado. Como indica el protocolo para los AEs (graves o no graves) con una relación de causalidad con la medicación en estudio los seguimientos por parte del investigador son requeridos hasta que el evento y sus secuelas se resuelva o estabilicen a un nivel aceptable por el investigador y Pfizer este de acuerdo con esa evaluación.
    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 Decision2011-09-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-09-09
    P. End of Trial
    P.End of Trial StatusCompleted
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA