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    Summary
    EudraCT Number:2014-000370-19
    Sponsor's Protocol Code Number:CO-1686-022
    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:2015-07-31
    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 number2014-000370-19
    A.3Full title of the trial
    TIGER-1: A Randomized, Open-label, Phase 2/3 Study of CO-1686 or Erlotinib as First-Line Treatment of Patients with EGFR-Mutant Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC)
    TIGER-1: Estudio de Fase II/III, aleatorizado, abierto, de CO-1686 o erlotinib como primera línea de tratamiento de pacientes con cáncer de pulmón no microcítico avanzado con mutaciones del receptor del factor de crecimiento epidérmico (EGFR)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2/3 clinical study to evaluate the safety and efficacy of the study medication CO-1686 compared to erlotinib in subjects with Non-Small Cell Lung Cancer
    Ensayo clínico de fase II/III para evaluar la seguridad y la eficacia de la medicación en estudio CO-1686 comparado con erlotinib en pacientes con cáncer de pulmón no microcítico
    A.3.2Name or abbreviated title of the trial where available
    TIGER-1
    A.4.1Sponsor's protocol code numberCO-1686-022
    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 SponsorClovis Oncology, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportClovis Oncology, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClovis Oncology UK Ltd
    B.5.2Functional name of contact pointDr Lindsey Rolfe
    B.5.3 Address:
    B.5.3.1Street AddressSheraton House, Castle Park
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeCB3 0AX
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number900 811 335
    B.5.6E-mailinfo@clovisoncology.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCO-1686
    D.3.2Product code CO-1686
    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 INNNot applicable
    D.3.9.1CAS number 1446700-26-0
    D.3.9.2Current sponsor codeCO-1686
    D.3.9.3Other descriptive nameCO-1686
    D.3.9.4EV Substance CodeSUB126980
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    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.3.1Product nameCO-1686
    D.3.2Product code CO-1686
    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 INNNot applicable
    D.3.9.1CAS number 1446700-26-0
    D.3.9.2Current sponsor codeCO-1686
    D.3.9.3Other descriptive nameCO-1686
    D.3.9.4EV Substance CodeSUB126980
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    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 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
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameErlotinib
    D.3.2Product code Erlotinib
    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.3.9.1CAS number 183321-74-6
    D.3.9.3Other descriptive nameERLOTINIB HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB16423MIG
    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: 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
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameErlotinib
    D.3.2Product code Erlotinib
    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.3.9.1CAS number 183321-74-6
    D.3.9.3Other descriptive nameERLOTINIB HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB16423MIG
    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: 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
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameErlotinib
    D.3.2Product code Erlotinib
    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.3.9.1CAS number 183321-74-6
    D.3.9.3Other descriptive nameERLOTINIB HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB16423MIG
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)
    Tratamiento de primera línea en pacientes con cáncer de pulmón no microcítico avanzado con mutaciones del receptor del factor de crecimiento epidérmico (EGFR)
    E.1.1.1Medical condition in easily understood language
    First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)
    Tratamiento de primera línea en pacientes con cáncer de pulmón no microcítico avanzado con mutaciones del receptor del factor de crecimiento epidérmico (EGFR)
    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 LLT
    E.1.2Classification code 10029514
    E.1.2Term Non-small cell lung cancer NOS
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the antitumor efficacy of oral single-agent CO-1686 with that of erlotinib as measured by PFS, when administered as a first-line targeted treatment to patients with EGFR-mutated, advanced/metastatic NSCLC
    Comparar la eficacia antitumoral del monotratamiento con CO-1686 por vía oral, con respecto a la del erlotinib, en función del SSP, administrado como tratamiento específico de primera línea en pacientes con CPNMC avanzado/metastásico y EGFR mutado
    E.2.2Secondary objectives of the trial
    - To compare secondary measures of clinical efficacy ORR, DR,and OS following treatment with CO-1686 versus erlotinib
    - To assess PFS, ORR, DR, and OS in patients with baseline T790M mutations based on central allele-specific polymerase chain reaction (PCR) EGFR mutation assay
    - To assess quality of life (QOL) using the patient-reported outcomes (PRO) of European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Quality of Life Questionnaire Lung Cancer module (EORTC QLQ-LC13), the Dermatology Life Quality Index (DLQI), and the EQ-5D instrument in patients receiving CO-1686 versus erlotinib
    ? To evaluate safety and tolerability of CO-1686 versus erlotinib in patients with advanced/metastatic NSCLC whose tumors have EGFR-activating mutations
    ? To determine PK of CO-1686 in this patient population using population PK (POPPK) methods and explore correlations between PK, exposure, response, and/or safety findings
    -Comparar las medidas secundarias de la eficacia clínica TRO, DR, y ST del CO-1686 en monoterapia por vía oral con las del erlotinib
    -Evaluar la SSP, TRO, DR, y ST en pacientes con mutaciones T790M en el momento inicial, en función del ensayo de la mutación EGFR mediante la reacción en cadena de la polimerasa alelo-específica central
    -Evaluar la calidad de vida mediante el cuestionario de RSP principal sobre calidad de vida de la Asociación Europea para la investigación y tratamiento del cáncer (EORTC QLQ-C30), el EORTC QLQ-LC13, el Índice de calidad de vida en dermatología (DLQI), y el cuestionario EQ-5D, en pacientes tratados con CO-1686, comparado con erlotinib
    -Evaluar la seguridad y tolerabilidad del CO-1686 comparado con erlotinib en pacientes con CPNMC con tumores con mutaciones activadoras del EGFR
    -Determinar la FC del CO-1686 en estos pacientes empleando métodos de FC poblacional (FCPOB) y buscar correlaciones entre FC, exposición, respuesta y/o datos de seguridad
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    To explore tissue and blood-based biomarkers that may be predictive of response or primary resistance to CO-1686 or erlotinib and investigate mechanisms of acquired resistance to treatment with CO-1686 or erlotinib using patient tumor tissue and blood samples
    Buscar biomarcadores tisulares y sanguíneos que pudieran predecir una respuesta o bien una resistencia primaria al CO-1686 o erlotinib, e investigar mecanismos de resistencia adquirida al tratamiento con CO-1686 o erlotinib en muestras de tejido tumoral y muestras de sangre de los pacientes
    E.3Principal inclusion criteria
    1. Histologically or cytologically confirmed metastatic or unresectable locally advanced, recurrent NSCLC
    2. Documented evidence of a tumor with one or more activating EGFR mutations excluding exon 20 insertion
    3. Have undergone a biopsy or surgical resection of either primary or metastatic tumor tissue within 60 days of planned randomization and have tissue available to send to sponsor lab or are able to undergo a biopsy during Screening and provide tissue to sponsor lab
    4. Measureable disease according to RECIST Version 1.1
    5. Life expectancy of at least 3 months
    6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
    7. Age >= 18 years (in certain territories, the minimum age requirement may be higher; e.g., age >= 20 years in Japan and Taiwan)
    8. Adequate hematological and biological function, confirmed by the following laboratory values e.g. Bone Marrow Function, Hepatic Function, Renal function and Electrolyte within normal range
    1. CPNMC avanzado a nivel local y no operable/metastásico, confirmado histológica o citológicamente
    2. Prueba confirmada de un tumor con mutaciones que activen el EGFR, mediante análisis a nivel local excluyendo inserciones en el exón 20
    3. Pacientes que se hayan sometido a una biopsia o resección quirúrgica de tejido tumoral, ya sea primario o metastásico, en los 60 días anteriores al día del tratamiento del estudio y cuenten con tejido biopsiado disponible para enviarlo a los laboratorios del promotor, o bien sean aptos para someterse a una biopsia durante la selección y proporcionar tejido a dichos laboratorios del promotor
    4. Enfermedad medible según RECIST, versión 1.1
    5. Esperanza de vida de al menos 3 meses
    6. Escala de estado funcional del Grupo Oncológico Cooperativo del Este (de EE. UU.) (ECOG) de entre 0 y 1
    7. Edad >= 18 años (en algunos países la edad mínima necesaria puede ser mayor, por ejemplo >= 20 en el caso de Japón y Taiwán)
    8. Actividad sanguínea y biológica suficiente, confirmada mediante las valoraciones analíticas siguientes: Actividad de la médula ósea, Actividad hepática, Actividad renal y Electrolitos dentro de límites normales
    E.4Principal exclusion criteria
    1. Documented evidence of an exon 20 insertion activating mutation in the EGFR gene
    2. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months has elapsed between the end of chemotherapy and randomization
    3. Active second malignancy; i.e., patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment
    -Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior to first day of study treatment, Cycle 1 Day 1 (C1D1)
    4. Known pre-existing interstitial lung disease (ILD)
    5. Brain metastases
    6. Treatment with prohibited medications [e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment (except corticosteroids and megesterol acetate), or immunotherapy] =< 14 days prior to first day of study treatment, Cycle 1 Day 1 (C1D1)
    7. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication (not known to affect QT interval) prior to C1D1
    8.Prior treatment with EGFR TKIs, CO-1686 or other drugs that target mutant EGFR
    9. Cardiac abnormalities or history
    10. Non-study related surgical procedures =< 7 days prior to C1D1. In all cases, the patient must be sufficiently recovered and stable before treatment administration.
    11. Females who are pregnant or breastfeeding
    12. Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of CO-1686 and 2 weeks after the last dose of erlotinib
    13. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)
    14. Any other reason the investigator considers the patient should not participate in the study
    1. Prueba documentada de una mutación activadora por inserción en el exón 20 del gen para EGFR
    2. Tratamiento anterior con quimioterapia citotóxica para CPNMC avanzado; la quimioterapia antineoplásica prequirúrgica/posquirúrgica está permitida siempre que hayan transcurrido por lo menos 6 meses entre el final de dicha quimioterapia y el momento de la aleatorización
    3. Segunda neoplasia maligna activa; es decir, se sabe que el paciente padece un cáncer posiblemente mortal para el que puede (aunque no necesariamente) estar siendo tratado en la actualidad
    - Los pacientes con antecedentes de neoplasia maligna que hayan sido completamente tratados y actualmente no presenten indicios de dicha neoplasia podrán inscribirse en el ensayo siempre y cuando todo el proceso quimioterapéutico haya finalizado > 6 meses antes y/o hayan recibido cualquier transplante de médula > 2 años antes del primer día del tratamiento del estudio, C1D1
    4. Neumopatía intersticial (NPI) preexistente confirmada
    5. Metástasis cerebrales
    6. Tratamiento con medicamentos no permitidos (por ejemplo, tratamiento antineoplásico concurrente como otra quimioterapia, radioterapia, tratamiento hormonal [excepto corticosteroides y acetato de megesterol], o inmunoterapia) =< 14 días antes del primer día del tratamiento del estudio, el C1D1
    7. Pacientes que actualmente estén recibiendo tratamiento con cualquier medicamento que pueda alargar el intervalo QT, si ese tratamiento no puede ni interrumpirse ni cambiarse a un medicamento diferente (que se sepa que no afecta al intervalo QT) antes del C1D1
    8. Tratamiento anterior con ITC EGFR, CO-1686 u otros fármacos cuya diana sea el EGFR mutante
    9. Anomalías o antecedentes cardíacos
    10. Intervenciones quirúrgicas no relacionadas con el estudio =< 7 días antes del C1D1. En todos los casos, el paciente deberá encontrarse lo suficientemente recuperado y estable antes de administrársele el tratamiento.
    11. Mujeres embarazadas o que están amamantando
    12. Rechazar el uso de métodos anticonceptivos suficientes en pacientes fértiles (mujeres y hombres) durante el estudio y 12 semanas después de la última dosis de CO-1686, y 2 semanas después de la última dosis de erlotinib
    13. Presencia de cualquier trastorno sistémico concurrente, grave o sin estabilizar, que resulte incompatible con el estudio clínico (por ejemplo, toxicomanía, enfermedad intercurrente no estabilizada incluida diabetes no controlada, infección activa, trombosis arterial y embolia pulmonar sintomática)
    14. Cualquier otro motivo por el que el investigador considere que el paciente no debe participar en el estudio
    E.5 End points
    E.5.1Primary end point(s)
    PFS according to RECIST Version 1.1 as determined by investigator review (invPFS)
    SSP según RECIST (versión 1.1) conforme lo determine el investigador mediante su evaluación (SSPinv)
    E.5.1.1Timepoint(s) of evaluation of this end point
    From start of treatment until it is clear that no further clinical benefit can be achieved.
    Desde el inicio del tratamiento hasta que se confirme que este no puede aportar ningún beneficio clínico
    E.5.2Secondary end point(s)
    - ORR and DR according to RECIST 1.1 as determined by investigator review, and OS
    - invPFS, ORR, DR, and OS in patients with baseline T790M mutations confirmed by central EGFR mutation assay
    - Change from baseline in QOL as measured using the PRO of EORTC QLQ-C30, EORTC QLQ-LC13, the DLQI, and the EQ-5D following treatment with CO-1686 versus erlotinib
    - Treatment-emergent AEs, laboratory abnormalities and ECG abnormalities
    - Plasma PK parameters for CO-1686 based on sparse sampling
    - TRO y DR según RECIST (versión 1.1) conforme lo determine el investigador mediante su evaluación y la ST
    - SSPinv, TRO, DR y ST en pacientes con mutaciones T790M en el momento inicial, confirmadas por ensayo central de mutación en el EGFR
    - Cambio desde el momento inicial en la CDV, valorado mediante los cuestionarios RSP de EORTC QLQ-C30, EORTC QLQ-LC13, el DLQI y el EQ-5D tras el tratamiento con CO-1686 en comparación con erlotinib
    - AAs durante el tratamiento, anomalías analíticas y electrocardiográficas (ECG)
    - Parámetros FC en plasma para CO-1686 a partir de muestreos puntuales
    E.5.2.1Timepoint(s) of evaluation of this end point
    From start of treatment until it is clear that no further clinical benefit can be achieved.
    Desde el inicio del tratamiento hasta que se confirme que este no puede aportar ningún beneficio clínico
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Erlotinib
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA19
    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
    France
    Germany
    Hong Kong
    Israel
    Italy
    Korea, Republic of
    Spain
    Taiwan
    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
    Upon discontinuation of original study treatment or crossover phase, all patients will enter the follow-up phase to monitor for survival status and subsequent NSCLC approximately every 3 months (12 +/- 1 week) until death or sponsor decision, whichever comes first.
    Cuando se finalice el tratamiento original del estudio, o el de la etapa de cambio de tratamiento, todos los pacientes pasarán a una fase de seguimiento para vigilar la supervivencia y posterior tratamiento para el CPNMC aproximadamente cada 3 meses (12 +/- 1 semanas), hasta el fallecimiento del paciente o hasta que el promotor decida, lo que suceda primero.
    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 months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 900
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 110
    F.4.2.2In the whole clinical trial 1200
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After the End of treatment the patients will return to their normal SOC medication.
    Los pacientes volverán a su fármaco habitual tras el fin del tratamiento
    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 Decision2015-10-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-10-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-07-03
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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