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    Summary
    EudraCT Number:2014-000370-19
    Sponsor's Protocol Code Number:CO-1686-022
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-09-03
    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 ConcernedFrance - ANSM
    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 : Étude randomisée, ouverte, de phase 2/3 visant à évaluer le CO-1686 ou l’Erlotinib comme traitement de première ligne chez des patients atteints d’un cancer du poumon non à petites cellules (CPNPC) muté EGFR à un stade avancé/métastatique
    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
    Une étude clinique de phase 2/3 pour évaluer l'innocuité et l'efficacité du CO-1686,le médicament à l'étude par rapport à l'erlotinib chezdes patients atteints d’un cancer du poumon non à petites cellules
    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 number+441223370037
    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)
    Traitement de première ligne des patients atteints d’un cancer du poumon non à petites cellules (CPNPC)
    E.1.1.1Medical condition in easily understood language
    First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)
    Traitement de première ligne des patients atteints d’un cancer du poumon non à petites cellules (CPNPC)
    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
    Comparer l’efficacité antitumorale du CO-1686 en monothérapie par voie orale avec celle de l’erlotinib mesurée par la survie sans progresion (SSP), lorsqu’il est administré comme traitement ciblé de première ligne à des patients atteints d’un CPNPC avancé/métastatique, avec mutation de l’EGFR.
    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
    E.2.3Trial contains a sub-study No
    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. No prior EGFR-directed therapy (e.g., erlotinib, gefitinib, neratinib, afatinib, AZD9291 or dacomitinib)
    5. Measureable disease according to RECIST Version 1.1
    6. Life expectancy of at least 3 months
    7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
    8. Age ≥ 18 years (in certain territories, the minimum age requirement may be higher; e.g., age ≥ 20 years in Japan and Taiwan)
    9. 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.CPNPC métastatique ou non résécable localement avancé, confirmé par examen histologique ou cytologique
    2.Preuve documentée d’une tumeur porteuse de une ou plisieurs mutations activatrices de l’EGFR excluant une insertion au niveau de l’exon 20
    3.Le patient a subi une biopsie ou une résection chirurgicale soit du tissu de la tumeur primaire soit d’une métastase dans les 60 jours précédant le jour de randomisation prévu et un échantillon de tissu est disponible pour envoi au laboratoire du promoteur ou est en mesure de subir une biopsie à la visite de sélection et de fournir un échantillon de tissu au laboratoire du promoteur.
    4. Aucune thérapie antérieure ciblée contre EGFR (par ex.erlotinib, gefitinib, neratinib, afatinib, AZD9291 or dacomitinib)
    5. Maladie mesurable selon RECIST version 1.1
    6.Espérance de vie d’au moins 3 mois
    7.Indice de performance ECOG (Eastern Cooperative Oncology Group) compris entre 0 et 1
    8.Patients âgés d'au moins 18 ans (dans certains pays, l’âge minimum requis peut être plus élevé, par exemple d'au moins 20 ans au Japon et à Taiwan)
    9.Fonction hématologique et biologique adéquate, confirmée par les valeurs biologiques dans la norme: Fonction de la moelle osseuse, Fonction hépatique, Fonction rénale, Électrolytes.
    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.Preuve documentée d’une insertion dans l’exon 20 activatrice de la mutation du gène EGFR
    2.Traitement antérieur par chimiothérapie cytotoxique pour un CPNPC avancé ; une chimiothérapie adjuvante ou néoadjuvante est autorisée si au moins 6 mois se sont écoulés entre la fin de la chimiothérapie et la randomisation
    3. Seconde tumeur maligne active, c.-à-d. patient connu pour avoir un cancer potentiellement fatal pour lequel il peut (mais pas nécessairement) actuellement prendre un traitement
    • Les patients ayant des antécédents de tumeur maligne complètement traitée, sans preuve actuelle de ce cancer, sont autorisés à participer à cet essai à condition que toutes les chimiothérapies aient été terminées > 6 mois avant et/ou que toute greffe de moelle osseuse ait été réalisée > 2 ans avant le premier jour du traitement à l’étude, C1J1
    4. Antécédents de pneumopathie interstitielle (PPI) connue
    5. Métastases cérébrales
    6. Traitement par des médicaments interdits (p. ex., traitement anticancéreux concomitant, notamment autre chimiothérapie, radiothérapie, hormonothérapie
    [sauf les corticostéroïdes et l’acétate de mégestérol], ou immunothérapie) au moins 14 jours avant le premier jour du traitement à l’étude, C1J1
    7. Les patients recevant actuellement un traitement par un médicament susceptible d’allonger l’intervalle QT ne pouvant pas être arrêté ou remplacé par un autre médicament (connu pour ne pas avoir d’effet sur l’intervalle QT) avant le C1J1
    8. Traitement antérieur par un EGFR-TKI (par ex., erlotinib, géfitinib, nératinib, afatinib, AZD9291, ou dacomitinib), CO-1686 ou d’autres médicaments ciblant le gène EGFR muté
    9. Anomalies ou antécédents cardiaques
    10. Interventions chirurgicales non liées à l’étude dans les 7 jours précédant le C1J1. Dans tous les cas, le patient doit être suffisamment rétabli et stable avant l’administration du traitement.
    11. Femmes enceintes ou qui allaitent
    12. Refus d’utiliser des moyens contraceptifs adéquats pour les patients en âge de procréer (hommes et femmes) pendant le traitement et pendant les 12 semaines après la dernière dose de CO-1686 et pendant les 2 semaines suivant la dernière dose d’erlotinib
    13. Présence de toute maladie systémique concomitante sérieuse ou instable, jugée incompatible avec l’étude clinique (p. ex. toxicomanie, maladie concomitante non contrôlée telle qu’un diabète, une infection active, une thrombose artérielle et une embolie pulmonaire symptomatique)
    14. Toute autre raison pour laquelle l’investigateur estime que le patient ne doit pas participer à l’étude
    E.5 End points
    E.5.1Primary end point(s)
    PFS according to RECIST Version 1.1 as determined by investigator review (invPFS)
    SSP selon les critères RECIST version 1.1, déterminés par l’évaluation de l’investigateur (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.
    Du début du traitement jusqu'à ce qu'il soit établi qu'aucun bénéfice clinique ne peut être atteint
    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 et DR, et TCM selon les critères RECIST version 1.1, déterminés par l’évaluation de l’investigateur, et SG
    • SSPinv, TRO, DR, et SG chez des patients porteurs de mutations T790M, à la visite de référence, confirmées par un test de recherche des mutations EGFR réalisé centralement
    • Variations par rapport à la visite de référence de la QdV mesurée à l’aide des RRP du questionnaire EORTC QLQ C30, EORTC QLQ LC13, de l’index DLQI, et du questionnaire EQ-5D après traitement par le CO-1686 par rapport à l’ertolinib
    • Événements indésirables (EI) apparus pendant le traitement, anomalies biologiques et anomalies à l’électrocardiogramme (ECG)
    • Paramètres PK plasmatiques du CO-1686 sur des échantillons épars
    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.
    Du début du traitement jusqu'à ce qu'il soit établi qu'aucun bénéfice clinique ne peut être atteint
    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 Yes
    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.
    A l'arrêt du traitement dans l'étude principale ou en phase de changement de bras de traitement, tous les patients entreront dans une phase de suivi afin que leur status vital et leur traitementultérieur contre le CPNPC puisse être surveillés environ tous les 3 mois (12 ± 1 semaines) jusqu'à la mort ou décision du promoteur, selon la première éventualité qui surviendra.
    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 state6
    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.
    Après la fin du traitement, les patients leur soins courants.
    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 Decision2015-09-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-08-26
    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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