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    Summary
    EudraCT Number:2022-002582-15
    Sponsor's Protocol Code Number:NerHer-1
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2023-03-07
    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 ConcernedAustria - BASG
    A.2EudraCT number2022-002582-15
    A.3Full title of the trial
    Phase II Study of Neratinib and Trastuzumab +/- Vinorelbine p.o.
    in Pre-treated Metastatic HER2-positive Breast Cancer (Ner-Her-1)
    Phase II Studie von Neratinib und Trastuzumab+/- Vinorelbine p.o.
    in vorbehandelten metastasierten Her2 positiven Brustkrebspatientinnen(Ner-Her-1)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase II Study mit Neratinib and Trastuzumab with or without Vinorelbine per mouth in patients with pretreated metastatic Her2- positive breast cancer
    Phase II Study mit Neratinib and Trastuzumab with or without Vinorelbine per mouth in patients with pretreated metastatic Her2- positive breast cancer
    A.3.2Name or abbreviated title of the trial where available
    NerHer-1
    A.4.1Sponsor's protocol code numberNerHer-1
    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 SponsorMedical University Graz
    B.1.3.4CountryAustria
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPierre Fabre
    B.4.2CountryAustria
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedical University Graz
    B.5.2Functional name of contact pointMarija Balic
    B.5.3 Address:
    B.5.3.1Street AddressAuebruggerplatz 15
    B.5.3.2Town/ cityGraz
    B.5.3.3Post code8036
    B.5.3.4CountryAustria
    B.5.4Telephone number0043316385 80556
    B.5.5Fax number0043316 385 14167
    B.5.6E-mailmarija.balic@medunigraz.at
    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 Yes
    D.2.1.1.1Trade name Nerlynx
    D.2.1.1.2Name of the Marketing Authorisation holderPierre Fabre Medicament, Les Cauquillous, 81506 Lavaurs, Cedex
    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 nameNeratinib
    D.3.2Product code PRD7433212
    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 INNNeratinib
    D.3.9.1CAS number 698387-09-6
    D.3.9.4EV Substance CodeSUB32232
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 Yes
    D.2.1.1.1Trade name Navelbine
    D.2.1.1.2Name of the Marketing Authorisation holderPierre Fabre Medicament, Les Cauquillous, 81506 Lavaurs, Cedex
    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 nameNavelbine
    D.3.4Pharmaceutical form Capsule
    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 INNVinorelbine
    D.3.9.1CAS number 71486-22-1
    D.3.9.4EV Substance CodeSUB00069MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Navelbine
    D.2.1.1.2Name of the Marketing Authorisation holderPierre Fabre Medicament, Les Cauquillous, 81506 Lavaurs, Cedex
    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 nameNavelbine
    D.3.2Product code L01CA04
    D.3.4Pharmaceutical form Capsule
    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 INNVinorelbine
    D.3.9.1CAS number 71486-22-1
    D.3.9.4EV Substance CodeSUB00069MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    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
    Patients with histologically confirmed Human Epidermal Growth Factor Receptor 2 (HER2)-positive metastatic breast cancer (mBC) pretreated with trastuzumab, pertuzumab, and/or trastuzumab emtansine (T-DM1) and/ or T-DXd and/or tucatinib
    Patientinnen mit histologisch bestätigten Human Epidermen Wachstumsfaktor Rezeptor 2 (Her2) positiven metasierten Brustkrebserkrankung, vorbehandelt mit Trastuzumab, Pertuzumab und/ oder Trastuzumab Emtansine (T-DM1) und/ oder Trastuzumab Deruxtecan und/ oder Tucatinib
    E.1.1.1Medical condition in easily understood language
    Patients with Her2 positive metastatic breast cancer who were pretreted with 2-4 lines of previous treatment
    Patientinnen mit Her2 positiven metastasierten Brustkrebserkrankung die mit 2-4 Therapielinien vorbehandelt wurden
    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 evaluate the proportion of patients alive and without progression at 6 months after study inclusion
    Anteil der Patientinnen die am Leben und ohne Progress 6 Monate nach Studieneinschluss sind
    E.2.2Secondary objectives of the trial
    • To estimate the proportion of patients alive and without extracranial progression at 6 months after study inclusion
    • To estimate the proportion of patients with complete or partial response according to RECIST 1.1 criteria
    • To quantify duration and depth of response in patients with any response according to RECIST 1.1 criteria
    • To estimate intracranial response rate (RANO-BM criteria) in patients with CNS metastases
    • To estimate progression free survival
    • To estimate overall survival
    • To evaluate the safety & tolerability of neratinib in combination with trastuzumab with or without vinorelbine on the basis of the incidence rate and severity of serious and non-serious AEs, with or without potential causal relationship to neratinib, trastuzumab, or vinorelbine. AEs may be identified by physical examination, laboratory parameters (hematologic and non-hematologic side effects), vital signs, echocardiography (ECHO)/ multigated acquisition (MUGA) scan, or electrocardiogram (ECG).
    Anteil der Patientinnen die am Leben und ohne extrakraniellen Progress 6 Monate nach Studieneinschluss sind
    Anteil der Patientinnen mit kompletten und partiellen Remission nach RECIST 1.1 Kriterien
    Quantifizierung der Dauer und der Tiefe des Ansprechens in Patientinnen mit einem Ansprechen nach den RECIST 1.1 Kriterien
    Intrakranielles Ansprechen nach RANO-BM Kriterien in Patientinnen mit primären ZNS Metastasen
    Progressionsfreie Überleben
    Gesamtüberleben
    Sicherheit und Tolerabilität von Neratinib in der Kombination mit Trastuzumab mit oder ohne Vinorelbine basierend auf der Inzidenzrate und Schwere der Nebenwirkungen, mit oder ohne potentiellen ursächlichen Verbindung zu Neratinib, Trastuzumab oder Vinorelbine.Nebenwirklungen können in der physikalischen Untersuchung, Laboruntersuchungen, Vitalparametern, Echokardiographie/ MUGA Scan oder EKG identifiziert werden.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Evaluation of biomarkers including cell free DNA, proportion of tumor DNA within the cell free DNA and mutational status
    Evaluierung der Biomarker einschliesslich zell-freie DNA, Anteil der Tumor DNA innerhalb der Zellen-freien DNA und Mutationstatus
    E.3Principal inclusion criteria
    • Histologically confirmed breast cancer (BC)
    • Radiologically documented metastatic disease
    • HER2-positive as defined by IHC 3+ and/or HER2/neu gene amplification
    • Measurable disease (RECIST 1.1)
    • Stable or newly diagnosed brain metastases or brain metastases progressing after prior local therapy allowed in the absence of an indication for immediate local treatment
    • No indication of leptomeningeal disease
    • Karnofsky Performance Status (KPS) ≥ 70%,
    Eastern Cooperative Oncology Group (ECOG) status ≤ 2.
    • Indication for systemic anti-HER2 treatment
    • Prior exposure to trastuzumab, pertuzumab, trastuzumab-emtansine (T-DM1) and/ or trastuzumab-deruxtecan (T-DXd) and/or tucatinib
    • Life expectancy of at least 3 months, as adjudicated by treating physician
    • Age ≥18 years
    • Patient must be able to tolerate therapy, and have adequate cardiac function (defined by baseline left ventricular ejection fraction (LVEF) ≥ 50%)
    • Adequate bone-marrow, liver and kidney function
    • Adequate treatment washout period / interval since local therapy before treatment start in this study, defined as:
    • Radiation therapy: ≥ 4 weeks
    • Chemotherapy, small-molecule targeted agents, anticancer hormonal therapy: ≥ 3 weeks
    • Antibody-based treatment: ≥ 4 weeks
    • Patient must be capable of understanding the purpose of the study and have given written informed consent
    • Patient must be able to swallow oral medication
    E.4Principal exclusion criteria
    • Metastatic BC other than HER2-positive disease
    • Use of any investigational agent within 21 days (antibody-based treatment 28 days) or within 5 half-lives of the compound prior to initiation of treatment, whichever is longer
    • History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 3 years prior to enrolment including contralateral BC
    • Major surgery, other than diagnostic surgery, within the last 4 weeks prior to enrolment
    • Prior extensive surgery of stomach and bowel affecting absorption or inducing malabsorption of oral treatment
    • Indication for immediate local therapy of central nervous system (CNS) disease as defined by local standard
    • Not less than 2 and not more than 4 previous therapy lines for metastatic breast cancer
    • Other planned anticancer therapy, including cytotoxic, targeted agents, immunotherapy, antibody, retinoid, or anti-cancer hormonal treatment
    • Concomitant radiotherapy
    • A history of uncontrolled seizures, CNS disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs
    • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), LVEF < 50%, arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities, and long QT syndrome (QTc interval > 450 msec)
    • Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) including acute and chronic infections with hepatitis B and C
    • Patients with severe hepatic impairment (Child-Pugh C)
    • Subjects who have current active inflammatory bowel disease such as Crohn’s disease or ulcerative colitis but not restricted to these
    • Inadequate hematological status at baseline prior to study entry: Dependency on red blood cell and/or platelet transfusions, absolute neutrophil count (ANC; segmented + bands) < 1.0 x 109/L; platelets < 100 x 109/L
    • Inadequate kidney function: serum-creatinine > 2 times upper normal limit
    • Hepatic dysfunction: total bilirubin > 1.5 times upper normal limit (> 3 in patients with liver metastases or known history of Gilbert’s disease); alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 3 times upper normal limit (> 5 in patients with liver metastases); serum albumin < 2.5 g/dL; INR ≥ 1.5
    • Patients with active opportunistic infections
    • Pregnant or lactating women. Women with childbearing potential must have a negative pregnancy test at screening.
    • Women with childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Acceptable contraception methods include the application of an intrauterine device, barrier method or total abstinence
    • Patients with known hypersensitivity to neratinib or trastuzumab or vinorelbine (if addition of vinorelbine is planned)
    • Patients with known substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results
    • Patients requiring concomitant use of chronic systemic (intravenous or oral) corticosteroids at doses higher than 4 mg dexamethasone per day or other immunosuppressive medications except for managing adverse events (AEs) (inhaled steroids or intra-articular steroid injections are permitted in this study)
    • Metastasierte Brustkrebserkrankung die nicght HER2-positive ist
    • Verwendung von einem der Medikamente innerhalb der letzten 21 Tage (Antikörper 28 Tage) oder innerhalb der 5 Halbwertszeiten des Medikaments vor der Initierung der Behandlung
    • Geschichte einer malignen Erkrankung ausser Plattenepithelkarzinom oder Basalzellkarzinom der Haut, In situ Karzinom der Zervix innerhalb der 3 Jahre vor Einschluss, einschliesslich kontralateraler Brustkrebs#
    Große chrirugische Eingriffe, die nicht diagnostische Chrirugie beinhalten, innerhalb der letzten 4 Wochen vor Einschluss
    • Indikation für unmittelbare lokale Therapie des ZNS definiert bei den lokalen Standards
    • Nicht weniger als 2 und nicht mehr als 4 Therapielinien für metastasierte Brustkrebserkrankung
    • Andere geplante Therapie gegen Krebs, einschliesslich zytotoxischer Therapie, Immuntherapie, Antikörper, Retinodie und sonstige antihormonelle Therapie
    • Konkomittante Bestrahlung
    • Vorgeschichte der unkontrollierten Krampfanfälle oder psychiatrischen Unfähigket nach dem Prüfer die negativ die Compliance der Studie beeinflussen könnte
    • Klinisch signifikatne kardiologische Erkrankung einschliesslich instabilen Angina, akuter ischämischer Infarkt 6 Monate vor dem Einschluss, Herzinsuffizienz (NYKA III-IV)m LVEF<50%, Arrhithmie ausser kontrolliert mit Therapie, ausgenommen Extrasystolen und minimale Leitabnormalitäten, long QT Intervall >450msec
    • Aktive Leber oder billiäre Erkrankung (mit Ausnahme von Gilbert Syndrom, asymtomatische Gallensteine, Lebermetastasen oder stabile chronische Lebererkrankung nach Beurteilung von Prüfarzt) einschliesslich akute und chronishe Infektionen mit Hepatitis B und C
    • Ernsthafte hepatische Einschränkung (Child Pugh C)
    • Aktive inflammatorische Darmerkrankung wie Morbud Crohn oder ulzerierende Colitis,
    • Inadäquater hämatologische Status vor Einschluss in die Studie, Notwendiger der Blutkonserven und/ oder Thrombozytenkonzentrate, absolute Neutrophilenzahl < 1.0 x 109/L; Thrombozyten < 100 x 109/L
    • Inadäquate Nierenfunktion Serumkreatinin > 2 faches vom oberen Normbereich
    • Hepatische Dysfunktion total Bilirubin > 1.5 fach vom oberen Normbereich (> 3 in Patientinnen mit Lebermetastasen oder bekanntem Mb Gilbert; alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 3 fach des oberen Normwertes (> 5 in Patientinnen mit Lebermetastasen); Serumalbumin < 2.5 g/dL; INR ≥ 1.5
    • Patientinnen mit aktiven opportunisticshen Infektionen
    • Schwangere oder stillende Frauen, Frauen im gebährfähigen Alter müssen einen negativen Schwangerschaftstest beim Screening haben
    • Frauen im gebährfähigen Alter, einschliesslich Frauen die die letzte Regelblutung vor weniger als einem Jahr vor Screening hatten, unfähig oder nicht willig sind adäquate Kontrazeption von Studienstart bis 1 Jahr nach der letzten Dosis der Protokolltherapie. Azzeptable Kontrazeptionsmethoden schliessen ein: Spirale, Barierremethoden oder totale Absitenz
    • Bekannte Überempfindlichkeit gegen Neratinib oder Trastuzumab oder Vinorelbine (falls Zusatzt von Vinorelbine geplant ist)
    • Patientinnen mit bekannter Abhängigkeit oder Komorbidität wie klinisch signifikante kardiologische oder psyhiche Verfassung di für den Prüfer mit Einnahme der Medikamente interferrieren könnte
    • Patientinnen die konkomittant intravenös oder oral Kortikosteroide höher als 4mg
    E.5 End points
    E.5.1Primary end point(s)
    • To evaluate the proportion of patients alive and without progression at 6 months after study inclusion
    Anteil der Patientinnen die am Leben und ohne Progress 6 Monate nach Einschluss in die Studie sind
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months after inclusion and 6 months after inclusion of the last patient
    6 Monate nach Einschluss und 6 Monate nach Einschluss der letzten Patientin
    E.5.2Secondary end point(s)
    • To estimate the proportion of patients alive and without extracranial progression at 6 months after study inclusion
    • To estimate the proportion of patients with complete or partial response according to RECIST 1.1 criteria
    • To quantify duration and depth of response in patients with any response according to RECIST 1.1 criteria
    • To estimate intracranial response rate (RANO-BM criteria) in patients with CNS metastases
    • To estimate progression free survival
    • To estimate overall survival
    • To evaluate the safety & tolerability of neratinib in combination with trastuzumab with or without vinorelbine on the basis of the incidence rate and severity of serious and non-serious AEs, with or without potential causal relationship to neratinib, trastuzumab, or vinorelbine. AEs may be identified by physical examination, laboratory parameters (hematologic and non-hematologic side effects), vital signs, echocardiography (ECHO)/ multigated acquisition (MUGA) scan, or electrocardiogram (ECG).
    Anteil der Patientinnen die am Leben und ohne extrakraniellen Progress 6 Monate nach Studieneinschluss sind
    Anteil der Patientinnen mit kompletten und partiellen Remission nach RECIST 1.1 Kriterien
    Quantifizierung der Dauer und der Tiefe des Ansprechens in Patientinnen mit einem Ansprechen nach den RECIST 1.1 Kriterien
    Intrakranielles Ansprechen nach RANO-BM Kriterien in Patientinnen mit primären ZNS Metastasen
    Progressionsfreie Überleben
    Gesamtüberleben
    Sicherheit und Tolerabilität von Neratinib in der Kombination mit Trastuzumab mit oder ohne Vinorelbine basierend auf der Inzidenzrate und Schwere der Nebenwirkungen, mit oder ohne potentiellen ursächlichen Verbindung zu Neratinib, Trastuzumab oder Vinorelbine.Nebenwirklungen können in der physikalischen Untersuchung, Laboruntersuchungen, Vitalparametern, Echokardiographie/ MUGA Scan oder EKG identifiziert werden.
    E.5.2.1Timepoint(s) of evaluation of this end point
    up to 6 months after inclusion of the last patient
    Bis 6 Monate nach Einschluss der letzten Patientin
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    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.6.13.1Other scope of the trial description
    Biomarker analyses of cell free DNA
    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 No
    E.8.1.1Randomised No
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned10
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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
    Trial will be terminated earlier if there is higher level of toxicity other then prespecified toxicity as defined in protocol
    Vorzeitiger Abbruch der Studie im Falle einer höheren Toxizität als die im Protokoll vordefinierte
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months36
    E.8.9.1In the Member State concerned days
    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: 65
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 state65
    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)
    According to standard
    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 Decision2023-03-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-01-26
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2024-01-19
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