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    Summary
    EudraCT Number:2019-003582-18
    Sponsor's Protocol Code Number:20190009
    National Competent Authority:Greece - EOF
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-04-01
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGreece - EOF
    A.2EudraCT number2019-003582-18
    A.3Full title of the trial
    A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of
    AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally
    Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated
    KRAS p.G12C
    «Μία Φάσης 3, Πολυκεντρική, Τυχαιοποιημένη, Ανοιχτού Σχεδιασμού, Ελεγχόμενη με Δραστικό Φάρμακο Δοκιμή του AMG 510 Έναντι της Ντοσεταξέλης για τη Θεραπεία Ασθενών με Τοπικά Προχωρημένο και Μη Εξαιρέσιμο ή Μεταστατικό NSCLC και Μετάλλαξη KRAS p.G12C, οι Οποίοι Είχαν Λάβει Προηγούμενη Θεραπεία»
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Study to Compare AMG 510 With Docetaxel in NSCLC Subjects
    With KRAS p.G12C Mutation (CodeBreak 200)
    «Μία Δοκιμή Φάσης 3 για τη Σύγκριση του AMG 510 με την Ντοσεταξέλη σε Ασθενείς με NSCLC και Μετάλλαξη KRAS p.G12C»
    A.4.1Sponsor's protocol code number20190009
    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 SponsorAmgen, 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 supportAmgen, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen Hellas Ε.Π.Ε
    B.5.2Functional name of contact pointMedical Information
    B.5.3 Address:
    B.5.3.1Street AddressΑγίου Κωνσταντίνου 59-61 Κτίριο Γ
    B.5.3.2Town/ cityΜαρούσι
    B.5.3.3Post code15124
    B.5.3.4CountryGreece
    B.5.4Telephone number+30 210 344 70 00
    B.5.5Fax number+30 210 344 70 50
    B.5.6E-mailmedinfo-amgen-hellas@amgen.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 nameAMG 510
    D.3.2Product code AMG 510
    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 INNPending
    D.3.9.3Other descriptive nameAMG 510
    D.3.9.4EV Substance CodeSUB193887
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    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 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.2.1.1.2Name of the Marketing Authorisation holderratiopharm GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 namedocetaxel
    D.3.2Product code docetaxel
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNdocetaxel
    D.3.9.3Other descriptive nameDOCETAXEL
    D.3.9.4EV Substance CodeSUB12492MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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
    Previously treated locally advanced and unresectable or metastatic nonsmall
    cell lung cancer (NSCLC) with KRAS p.G12C mutation
    Ασθενείς με τοπικά προχωρημένο και μη εξαιρέσιμο ή μεταστατικό NSCLC με μετάλλαξη KRAS p.G12C, οι οποίοι είχαν λάβει προηγούμενη θεραπεία
    E.1.1.1Medical condition in easily understood language
    Previously treated locally advanced and unresectable or metastatic nonsmall
    cell lung cancer (NSCLC) with KRAS p.G12C mutation
    Ασθενείς με τοπικά προχωρημένο και μη εξαιρέσιμο ή μεταστατικό NSCLC με μετάλλαξη KRAS p.G12C, οι οποίοι είχαν λάβει προηγούμενη θεραπεία
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    •To compare the efficacy of AMG 510 versus docetaxel as assessed by progression-free survival (PFS) in previously treated subjects with KRAS p.G12C mutated nonsmall cell lung cancer (NSCLC)
    Η σύγκριση της αποτελεσματικότητας του AMG 510 έναντι της ντοσεταξέλης, όπως αξιολογείται από την επιβίωση χωρίς εξέλιξη της νόσου (PFS) σε ασθενείς με μη μικροκυτταρικό καρκίνο του πνεύμονα (NSCLC) και μετάλλαξη KRAS p.G12C, οι οποίοι είχαν λάβει προηγούμενη θεραπεία
    E.2.2Secondary objectives of the trial
    •To compare the efficacy of AMG 510 Versus docetaxel as assessed by:
    - Overall Survival (OS)
    - Objective response rate (ORR)
    •To compare patient-reported outcomes (PRO) as assessed by:
    - European Organization for Research and Treatment of Cancer Quality of life Questionnaire Core 13 (EORTC QLQ-LC13) and European
    Organization for Research and Treatment of Cancer Quality-of-life
    Questionnaire Core 30 (EORTC QLQ-C30)
    •To compare efficacy of AMG 510 versus docetaxel as assessed by:
    - duration of response (DOR), time to response (TTR), and disease control rate (DCR)
    •To compare the safety and tolerability of AMG 510 versus docetaxel
    •To compare the effect of treatment with AMG 510 on other treatment
    and disease related symptoms, and health related quality of life relative to docetaxel
    •To characterize the pharmacokinetics (PK) of AMG 510 and its major metabolites
    Παρακαλούμε λογω έλλειψης χώρου όπως ανατρέξετε στο πρωτόκολλο
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Subject or subject's legally acceptable representative has provided informed consent prior to initiation of any study specific activities/procedures.
    • Age ≥ 18 years of age
    • Have documentation of KRAS p.G12C mutation confirmed by central
    testing through the current protocol or Amgen Study 20190294 prior to enrollment.
    • Subjects will have received and progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease. Prior treatment must include a platinum-based doublet chemotherapy and checkpoint inhibitor for advanced or metastatic disease, either given as one line of therapy or as individual lines of therapy unless the subject has a medical contraindication to one of the required therapies. If the subject has a medical contraindication to a required therapy, the subject may be enrolled only after the investigator discusses and obtains approval from the Amgen medical monitor.
    a) Adjuvant therapy will count as a line of therapy if the subject progressed on or within 6 months of adjuvant therapy administration.
    b) In locally advanced and unresectable NSCLC, disease progression on or within 6 months of end of prior curatively intended multimodal therapy will count as a line of therapy. If chemoradiation is followed by planned systemic therapy without documented progression between chemoradiation and systemic therapy, the entire treatment course
    counts as one line of therapy.
    • Subjects must have archived tumor tissue samples (formalin fixed, paraffin embedded [FFPE] sample [FFPE of excisional, core needle, or fine needle aspirates] collected within 5 years) or be willing to undergo pre-treatment tumor biopsy (excisional, core needle, or fine needle aspirates) prior to enrollment.
    • Measurable disease per RECIST v1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.
    • ECOG Performance Status of ≤ 1
    • Adequate hematologic laboratory assessments
    • Life expectancy of > 3 months, in the opinion of the investigator
    • Adequate liver function
    • International normalized ratio (INR) and activated partial
    thromboplastin time ≤ 1.5 x ULN
    • Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 mL/min.
    Cockcroft-Gault formula will be used for creatinine clearance calculation.
    Twenty-four hour urine collection is not required but is allowed.
    • QTc ≤ 470 msec in females and ≤ 450 msec in males
    • Ability to take oral medications and willing to record daily adherence
    to investigational product
    • Ο ασθενής ή ο νόμιμος εκπρόσωπός του έχει παράσχει συναίνεση μετά από ενημέρωση πριν από την έναρξη οποιασδήποτε δραστηριότητας/διαδικασίας αυτής της δοκιμής.
    • Ηλικία  18 ετών
    • Έχουν τεκμηρίωση της μετάλλαξης KRAS p.G12C που έχει επιβεβαιωθεί μέσω ελέγχου από το κεντρικό εργαστήριο στο πλαίσιο του τρέχοντος πρωτοκόλλου ή της Δοκιμής 20190294 της Amgen πριν από την ένταξη στη δοκιμή.
    • Οι ασθενείς θα έχουν παρουσιάσει εξέλιξη της νόσου ή υποτροπή της νόσου κατά τη διάρκεια τουλάχιστον 1 προηγούμενης συστηματικής θεραπείας για την τοπικά προχωρημένη και μη εξαιρέσιμη ή μεταστατική νόσο ή μετά από τη λήψη αυτής της θεραπείας. Η προηγούμενη θεραπεία θα πρέπει να περιλαμβάνει μία διπλή χημειοθεραπεία με βάση την πλατίνη και αναστολέα ανοσολογικού σημείου ελέγχου για την προχωρημένη ή μεταστατική νόσο, είτε χορηγείται ως μία γραμμή θεραπείας είτε ως μεμονωμένες γραμμές θεραπείας, εκτός εάν ο ασθενής έχει ιατρική αντένδειξη σε κάποια από τις απαιτούμενες θεραπείες. Εάν ο ασθενής έχει ιατρική αντένδειξη σε μία απαιτούμενη από το πρωτόκολλο θεραπεία, θα μπορεί να ενταχθεί στη δοκιμή μόνο αφού ο ερευνητής συζητήσει με τον ιατρικό επιτηρητή της Amgen και εξασφαλίσει την έγκρισή του.
    o Η επικουρική θεραπεία θα εκλαμβάνεται ως γραμμή θεραπείας εάν ο ασθενής έχει παρουσιάσει εξέλιξη της νόσου στη διάρκεια της χορήγησης της επικουρικής θεραπείας ή εντός ενός διαστήματος 6 μηνών από τη χορήγησή της.
    o Στον τοπικά προχωρημένο και μη εξαιρέσιμο NSCLC, η εξέλιξη της νόσου στη διάρκεια της χορήγησης της προηγούμενης πολυσχιδούς θεραπείας με πρόθεση την ίαση ή εντός ενός διαστήματος 6 μηνών από τη διακοπή της θα εκλαμβάνεται ως μία γραμμή θεραπείας. Εάν η χημειοακτινοθεραπεία ακολουθείται από προγραμματισμένη συστηματική θεραπεία χωρίς τεκμηριωμένη εξέλιξη της νόσου μεταξύ της χημειοακτινοθεραπείας και της συστηματικής θεραπείας, ολόκληρο το θεραπευτικό σχήμα εκλαμβάνεται ως μία γραμμή θεραπείας.
    • Οι ασθενείς θα πρέπει να έχουν αρχειοθετημένα δείγματα καρκινικού ιστού (δείγμα μονιμοποιημένο με φορμαλίνη και εμπεδωμένο σε παραφίνη [FFPE] [FFPE με εκτομή, με κόπτουσα βελόνη ή με αναρρόφηση δια λεπτής βελόνης] που έχει συλλεχθεί εντός 5 ετών) ή να είναι πρόθυμοι να υποβληθούν σε βιοψία όγκου πριν από τη λήψη της θεραπείας (με εκτομή, με κόπτουσα βελόνη ή με αναρρόφηση δια λεπτής βελόνης) προτού ενταχθούν στη δοκιμή.
    • Μετρήσιμη νόσος σύμφωνα με τα κριτήρια RECIST 1.1. Οι βλάβες που έχουν προηγουμένως υποβληθεί σε ακτινοβολία δεν θεωρούνται μετρήσιμες, εκτός εάν έχουν παρουσιάσει εξέλιξη μετά την ακτινοβολία.
    • Κατάσταση Απόδοσης  1 κατά ECOG
    • Επαρκείς αιματολογικές εργαστηριακές αξιολογήσεις
    • Προσδόκιμο επιβίωσης > 3 μηνών, κατά τη γνώμη του ερευνητή
    o Επαρκής ηπατική λειτουργία,
    o Διεθνής κανονικοποιημένος λόγος (INR) και χρόνος ενεργοποιημένης μερικής θρομβοπλαστίνης 1,5 φορές το ULN
    o Κρεατινίνη ορού  1,5 φορές το ULN Ή κάθαρση κρεατινίνης  60 mL/λεπτό. Ο τύπος Cockcroft-Gault θα χρησιμοποιείται για τον υπολογισμό της κάθαρσης κρεατινίνης. Δεν απαιτείται, αλλά επιτρέπεται, η συλλογή ούρων 24ώρου.
    o QTc  470 msec στις γυναίκες και  450 msec στους άνδρες (με βάση τον μέσο όρο των εις τριπλούν ελέγχων)
    • Ικανότητα λήψης φαρμακευτικών αγωγών από το στόμα και προθυμία καταγραφής της ημερήσιας συμμόρφωσης με το δοσολογικό πρόγραμμα του υπό έρευνα προϊόντος
    E.4Principal exclusion criteria
    • Subjects have received prior docetaxel in unresectable or metastatic setting.
    • Mixed small-cell lung cancer and NSCLC histology
    • Previously identified driver mutation other than KRAS p.G12C for which an approved therapy is available (including EGFR, ALK, etc).
    • Active brain metastases. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria:
    a) residual neurological symptoms grade ≤ 2; b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and c) follow-up MRI performed within 30 days prior to enrollment shows no progression or new lesions appearing.
    • Leptomeningeal disease.
    • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly.
    Patients with PleurX catheters in place may be considered for the study with Medical Monitor approval.

    Other Medical Conditions
    • Known history of Human Immunodeficiency Virus (HIV) infection
    • Exclusion of hepatitis infection based on the following results and/or
    criteria:
    a) Positive hepatitis B surface antigen (HepBsAg)
    b) Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B core antibody testing is not required for screening, however if this is done and is positive, then hepatitis B surface antibody [Anti-HBs] testing is necessary. Undetectable anti HBs in this setting would
    suggest unclear and possible infection, and needs exclusion).
    c) Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase chain reaction is necessary. Detectable Hepatitis C virus RNA renders the subject ineligible.
    • Malignancy other than NSCLC within 3 years prior to randomization, with the exception of those with a negligible risk of metastases or death and treated with expected curative outcome.
    • Major surgery within 28 days of study day 1
    • Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication.
    • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to study day 1, unstable arrhythmias or unstable angina.
    • Severe infections within 4 weeks prior to randomization including, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia.
    • Therapeutic oral or intravenous antibiotics within 2 weeks prior to randomization. Prophylactic antibiotics are allowed with Amgen medical monitor approval.
    • Current CTCAE version 5.0 grade ≥ 2 peripheral neuropathy
    Prior/Concomitant Therapy
    • Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to CTCAE version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (any grade allowed) or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 6 months),
    endocrine adverse events that are stably maintained on appropriate replacement therapy.
    • Anti-tumor therapy within 4 weeks of study day 1; Please note that bisphosphonates or anti-Receptor Activator of Nuclear Factor Kappa Beta Ligand (anti RANKL) antibody therapy is allowed if needed for management of hypercalcemia or for prevention of skeletal events.
    • Therapeutic or palliative radiation therapy within 2 weeks of study day 1. Subjects must have recovered from all radiotherapy related toxicity to CTCAE version 5.0 grade 1 or less with the exception of alopecia (any grade of alopecia allowed).
    • Other investigational procedures are excluded
    • Previous treatment with AMG 510 or other KRAS G12C inhibitor
    • History of severe hypersensitivity to docetaxel or to other drugs formulated with polysorbate 80, or known sensitivity to any of the products or components to be administered during dosing.
    Παρακαλούμε λογω έλλειψης χώρου όπως ανατρέξετε στο πρωτόκολλο
    E.5 End points
    E.5.1Primary end point(s)
    • PFS - defined as time from randomization until disease progression or death from any cause, whichever occurs first for all subjects.
    •PFS – ορίζεται ως ο χρόνος από την τυχαιοποίηση έως την εξέλιξη της νόσου ή τον θάνατο πάσης αιτιολογίας, όποιο από τα δύο προκύψει πρώτο για όλους τους ασθενείς
    E.5.1.1Timepoint(s) of evaluation of this end point
    The timing for the PA of PFS will be event driven. If PFS early success is
    achieved in the IA, the IA will serve the purpose of PA of PFS.
    The final analysis of the study will be done when the last subject
    completes LTFU.
    Το χρονικό σημείο διεξαγωγής της ΚΑ της PFS θα είναι καθοδηγούμενο από τα συμβάντα. Εάν προκύψει πρόωρη επιτυχία ως προς την PFS στην ΕΑ, η ΕΑ θα αποτελεί την ΚΑ της PFS. Η τελική ανάλυση της δοκιμής θα πραγματοποιηθεί όταν ο τελευταίος ασθενής ολοκληρώσει την LTFU.
    E.5.2Secondary end point(s)
    • Overall survival - defined as time from randomization until death from any cause.
    • Objective response (complete response [CR] + partial response [PR]), assessed per RECIST v1.1. Response will be assessed by BICR.
    • Change from baseline over time to week 12 in disease related symptoms of:
    o Dyspnea as measured by a 4 item dyspnea domain from QLQ-C30 and QLQ-LC13
    o Cough as measured by QLQ-LC13
    o Chest Pain as measured by QLQ-LC13
    • Change from baseline over time to week 12 in
    o Physical functioning as measured by QLQ-C30
    o Global health status as measured by QLQ-C30
    • Duration of response - defined as time from first evidence of PR or CR to disease progression or death due to any cause, whichever occurs first.
    • Συνολική επιβίωση - ορίζεται ως χρονικό διάστημα από την τυχαιοποίηση έως τον θάνατο πάσης αιτιολογίας.
    • Αντικειμενική ανταπόκριση (πλήρης ανταπόκριση [CR] + μερική ανταπόκριση [PR]), όπως αξιολογείται σύμφωνα με τα κριτήρια RECIST 1.1. Η ανταπόκριση θα αξιολογείται από την BICR.
    • Μεταβολή από την έναρξη της δοκιμής σε συνάρτηση με τον χρόνο έως την εβδομάδα 12
    στα ακόλουθα σχετιζόμενα με τη νόσο συμπτώματα:
    • Δύσπνοια, όπως μετριέται μέσω ενός πεδίου δύσπνοιας 4 θεμάτων από τα QLQ-C30
    • και QLQ LC13
    • Βήχας, όπως μετριέται μέσω του QLQ LC13
    • Θωρακικό Άλγος, όπως μετριέται μέσω του QLQ-LC13
    • Μεταβολή από την έναρξη της δοκιμής σε συνάρτηση με τον χρόνο έως την εβδομάδα 12 σε
    o Σωματική λειτουργικότητα, όπως μετριέται μέσω QLQ-C30
    o Συνολική κατάσταση της υγείας, όπως μετριέται μέσω QLQ-C30
    • Διάρκεια της ανταπόκρισης – ορίζεται ως ο χρόνος από την πρώτη ένδειξη PR ή CR έως την εξέλιξη της νόσου ή τον θάνατο πάσης αιτιολογίας, όποιο από τα δύο προκύψει πρώτο
    E.5.2.1Timepoint(s) of evaluation of this end point
    The timing for the PA of PFS will be event driven. If PFS early success is achieved in the IA, the IA will serve the purpose of PA of PFS.
    The final analysis of the study will be done when the last subject completes LTFU.
    Η επίσκεψη ολοκλήρωσης της δοκιμής για έναν μεμονωμένο ασθενή ορίζεται ως η ημερομηνία της τελευταίας επικοινωνίας στο πλαίσιο της δοκιμής (π.χ. επίσκεψη LFTU) όταν οι αξιολογήσεις ή οι διαδικασίες θα έχουν πραγματοποιηθεί
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other 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 No
    E.8.2.3.1Comparator description
    docetaxel
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA160
    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
    Australia
    Belgium
    Brazil
    Canada
    China
    Denmark
    Finland
    France
    Germany
    Greece
    Hungary
    Italy
    Japan
    Korea, Republic of
    Netherlands
    Poland
    Portugal
    Russian Federation
    Spain
    Sweden
    Switzerland
    Taiwan
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study visit for an individual subject is defined as the date of the final study contact (eg, LFTU visit) when assessments or procedures are done.
    Η επίσκεψη ολοκλήρωσης της δοκιμής για έναν μεμονωμένο ασθενή ορίζεται ως η ημερομηνία της τελευταίας επικοινωνίας στο πλαίσιο της δοκιμής (π.χ. επίσκεψη LFTU) όταν οι αξιολογήσεις ή οι διαδικασίες θα έχουν πραγματοποιηθεί
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 500
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 150
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 400
    F.4.2.2In the whole clinical trial 650
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    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 Decision2020-04-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-27
    P. End of Trial
    P.End of Trial StatusOngoing
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