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    Summary
    EudraCT Number:2014-000370-19
    Sponsor's Protocol Code Number:CO-1686-022
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-02-15
    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 ConcernedItaly - Italian Medicines Agency
    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: Studio di Fase 2/3, randomizzato, in aperto su CO-1686 o Erlotinib come trattamento di prima linea in pazienti con carcinoma polmonare non a piccole cellule (Non-Small Cell Lung Cancer, NSCLC) in stadio avanzato/metastatico con EGFR mutante
    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
    Studio clinico di Fase 2/3 per valutare la sicurezza e l'efficacia del farmaco in studio CO-1686 rispetto a erlotinib in pazienti con carcinoma polmonare non a piccole cellule
    A.3.2Name or abbreviated title of the trial where available
    TIGER-1
    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 number00441223370037
    B.5.5Fax number0000
    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 IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 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 IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNERLOTINIB CLORIDRATO
    D.3.9.1CAS number 183321-74-6
    D.3.9.2Current sponsor codeERLOTINIB CLORIDRATO
    D.3.9.3Other descriptive nameERLOTINIB CLORIDRATO
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 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 IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNERLOTINIB CLORIDRATO
    D.3.9.1CAS number 183321-74-6
    D.3.9.2Current sponsor codeERLOTINIB CLORIDRATO
    D.3.9.3Other descriptive nameERLOTINIB CLORIDRATO
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 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 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 IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNERLOTINIB CLORIDRATO
    D.3.9.1CAS number 183321-74-6
    D.3.9.2Current sponsor codeERLOTINIB CLORIDRATO
    D.3.9.3Other descriptive nameERLOTINIB CLORIDRATO
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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)
    Trattamento di prima linea in pazienti con carcinoma polmonare non a piccole cellule (Non-Small Cell Lung Cancer, NSCLC) in stadio avanzato con EGFR mutante
    E.1.1.1Medical condition in easily understood language
    First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)
    Trattamento di prima linea in pazienti con carcinoma polmonare non a piccole cellule (Non-Small Cell Lung Cancer, NSCLC) in stadio avanzato con EGFR mutante
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    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
    Confrontare l’efficacia antitumorale di CO-1686 per via orale in monoterapia con quella di erlotinib misurata in termini di PFS quando somministrato come trattamento mirato di prima linea a pazienti affetti da NSCLC in stadio avanzato/metastatico con EGFR mutato
    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 EGFRactivating
    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
    • Confrontare le misure secondarie di efficacia clinica ORR, DR e OS dopo il trattamento CO-1686 verso erlotinib
    • Valutare PFS, ORR, DR e OS nei pazienti con mutazioni T790M al basale sulla base del test delle mutazioni dell’EGFR mediante reazione a catena della polimerasi (PCR) allele-specifica eseguito a livello centrale
    • Valutare la qualità della vita (QOL) utilizzando il Questionario di base sulla qualità della vita (PRO) dell’Organizzazione Europea per la Ricerca e il Trattamento del Cancro Core Quality of Life Questionnaire (EORTC QLQ-C30) e il Modulo sul carcinoma polmonare del Questionario sulla qualità della vita (EORTC QLQ-LC13), l’Indice di qualità della vita in dermatologia (DLQI) e lo strumento EQ-5D) nei pazienti che ricevono trattamento con CO-1686 rispetto a erlotinib
    • Valutare la sicurezza e la tollerabilità di CO-1686 rispetto a erlotinib in pazienti con NSCLC in stadio avanzato/metastatico i cui tumori presentano mutazioni attivanti l’EGFR
    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. NSCLC metastatico, localmente avanzato o non resecabile confermato istologicamente o citologicamente
    2. Presenza documentata di tumore con una o più mutazioni attivanti l’EGFR fatta eccezione per i pazienti con presenza documentata di inserzione dell’esone 20
    3. Essere stati sottoposti a biopsia o resezione chirurgica di tessuto tumorale primario o metastatico entro 60 giorni dal primo giorno del trattamento dello studio e disporre di tessuto da inviare ai laboratori dello sponsor o essere in grado di sottoporsi a biopsia durante lo screening e fornire tessuto ai laboratori dello sponsor
    4. Nessuna terapia EGFR-diretto precedente (ad esempio, erlotinib, gefitinib, neratinib,
    afatinib, AZD9291 o dacomitinib)
    5. Malattia misurabile secondo i criteri RECIST Versione 1.1
    6. Aspettativa di vita di almeno 3 mesi
    7. Stato di validità ECOG (Eastern Cooperative Oncology Group) da 0 a 1
    8. Età ≥18 anni (in alcune zone, l’età minima richiesta potrebbe essere più alta, ad es., ≥20 anni in Giappone e Taiwan)
    9. Funzionalità ematologica e biologica adeguata, confermata dai seguenti valori di laboratorio ad es. Funzionalità del Midollo Osseo, Funzionalità Epatica, Funzionalità Renale ed Elettroliti entro i valori normali
    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. Presenza documentata di una mutazione attivante con inserzione dell’esone 20 nel gene EGFR
    2. Precedente trattamento con chemioterapia citotossica per l’NSCLC avanzato; la chemioterapia neoadiuvante/adiuvante è consentita se sono trascorsi almeno 6 mesi tra il termine della chemioterapia e la randomizzazione
    3. Seconda malignità attiva, ossia, paziente con presenza nota di tumore potenzialmente fatale per il quale attualmente potrebbe (ma non necessariamente) ricevere trattamento
    • ai pazienti con anamnesi di malignità completamente trattata e attualmente senza evidenza di tale tumore è consentito arruolarsi nella sperimentazione purché sia stata completata tutta la chemioterapia > 6 mesi prima e/o il trapianto di midollo osseo > 2 anni prima del primo giorno di trattamento dello studio, Ciclo 1 Giorno 1 (C1G1)
    4. Nota interstiziopatia polmonare (interstitial lung disease, ILD) preesistente
    5. Metastasi cerebrali
    6. Trattamento con farmaci proibiti (ad es., terapia antitumorale concomitante tra cui altra chemioterapia, radiazione, trattamento ormonale (tranne i corticosteroidi e il megesterolo acetato) o immunoterapia) ≤14 giorni prima del primo giorno di trattamento dello studio, Ciclo 1 Giorno 1 (C1G1)
    7. Pazienti attualmente in trattamento con qualsiasi farmaco che potenzialmente possa prolungare l’intervallo QT, se tale trattamento non può essere interrotto o non è possibile passare a un farmaco diverso (non noto per incidere sull’intervallo QT) prima del C1G1
    8. Precedente trattamento con TKI dell’EGFR, CO-1686 o altri farmaci che colpiscono l’EGFR mutante
    9. Anomalie cardiache o anamnesi
    10. Procedure chirurgiche non correlate allo studio ≤ 7 giorni prima del C1G1. In tutti i casi, il paziente dovrà essersi ripreso a sufficienza ed essere stabile prima della somministrazione del trattamento.
    11. Soggetti di sesso femminile in stato di gravidanza o di allattamento al seno
    12. Rifiuto da parte dei pazienti fertili (di sesso maschile e femminile) di utilizzare metodi contraccettivi adeguati durante il trattamento dello studio e per 12 settimane dopo l’ultima dose di CO-1686 e due settimane dopo l’ultima dose di erlotinib
    13. Presenza di qualsiasi disturbo sistemico concomitante grave o instabile, incompatibile con lo studio clinico (ad es., abuso di sostanze stupefacenti, malattia intercorrente non controllata tra cui diabete non controllato, infezione attiva, trombosi arteriosa ed embolia polmonare sintomatica)
    14. Qualsiasi altra ragione per cui lo sperimentatore ritenga che il paziente non debba partecipare allo studio
    E.5 End points
    E.5.1Primary end point(s)
    PFS according to RECIST Version 1.1 as determined by investigator review (invPFS)
    PFS secondo i criteri RECIST Versione 1.1, determinata dall’analisi dello sperimentatore (PFSsper)
    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.
    Dall'inizio del trattamento fino a quando è chiaro che nessun ulteriore beneficio clinico può essere realizzato.
    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
    • ORR e DR secondo i criteri RECIST Versione 1.1, determinati dall’analisi dello sperimentatore, e OS
    • PFSsper, ORR, DR e OS nei pazienti con mutazioni T790M al basale confermate dal test delle mutazioni dell’EGFR eseguito a livello centrale
    • Variazione rispetto al basale della QOL, misurata utilizzando i PRO di EORTC QLQ C30, EORTC QLQ LC13, l’indice DLQI e il questionario EQ-5D in seguito al trattamento con CO-1686 rispetto a erlotinib
    • (EA emergenti dal trattamento, anomalie di laboratorio e anomalie nell’elettrocardiogramma (ECG)
    • Parametri PK plasmatici per CO-1686 basati su campionamento ridotto
    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.
    Dall'inizio del trattamento fino a quando è chiaro che nessun ulteriore beneficio clinico può essere realizzato.
    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) 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 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
    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 concerned3
    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 Information not present in EudraCT
    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, Democratic People's Republic of
    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.
    Dopo l'interruzione del trattamento originale dello studio o della fase di crossover, tutti i pazienti entreranno nella fase di follow-up per monitorare lo stato di sopravvivenza e la successiva NSCLC circa ogni 3 mesi (12 ± 1 settimana) fino alla morte o alla decisione dello sponsor, qualunque avvenga prima.
    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 months3
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    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.1.1Number of subjects for this age range: 1
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    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 Yes
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state4
    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.
    Dopo il termine di trattamento i pazienti ritorneranno alla loro medicazione standard di cura.
    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 Decision2015-10-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-15
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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