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    Summary
    EudraCT Number:2016-001925-15
    Sponsor's Protocol Code Number:ISS20159321
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-08-23
    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 ConcernedGermany - PEI
    A.2EudraCT number2016-001925-15
    A.3Full title of the trial
    Evaluation of immunological effects of the RANKL-inhibitor Denosumab when administered concurrently with PD1-blocking antibodies (Nivolumab, Pembrolizumab) in patients with metastatic malignant melanoma with bone involvement
    Evaluierung immunologischer Effekte des RANKL-Inhibitors Denosumab bei gleichzeitiger Gabe von PD-1 blockierenden Antikörpern (Nivolumab, Pembrolizumab) bei Patienten mit metastasiertem malignem Melanom mit Knochenmetastasen
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Effects of a treatment with Denosumab, applied together with either Nivolumab oder Pembrolizumab, in patients with skin cancer and bone metastases
    Effekte einer Behandlung mit Denosumab in Kombination mit etnweder Nivolumab oder Pembrolizumab auf Patienten mit Hautkrebs und Knochenmetastasen
    A.3.2Name or abbreviated title of the trial where available
    BONEMET
    BONEMET
    A.4.1Sponsor's protocol code numberISS20159321
    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 SponsorAlcedis GmbH
    B.1.3.4CountryGermany
    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 GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedizinische Hochschule Hannover
    B.5.2Functional name of contact pointSkin Cancer Center, Dermatology
    B.5.3 Address:
    B.5.3.1Street AddressCarl Neuberg Str. 1
    B.5.3.2Town/ cityHanover
    B.5.3.3Post codeD-30625
    B.5.3.4CountryGermany
    B.5.4Telephone number+495115320
    B.5.5Fax number+49511532161017
    B.5.6E-mailGutzmer.Ralf@mh-hannover.de
    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 XGEVA
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe B.V. Minervum 7061 NL-4817 ZK Breda Niederlande
    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 nameDENOSUMAB
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    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) Yes
    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 Yes
    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.2.1.2Country 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 nameOPDIVO
    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 INNNIVOLUMAB
    D.3.9.1CAS number 946414-94-4
    D.3.9.3Other descriptive nameNIVOLUMAB
    D.3.9.4EV Substance CodeSUB122750
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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) Yes
    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 Yes
    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.2.1.2Country 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 nameKEYTRUDA
    D.3.4Pharmaceutical form Powder for 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 INNPEMBROLIZUMAB
    D.3.9.1CAS number 1374853-91-4
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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 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.2.1.2Country 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 nameYERVOY
    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 INNIPILIMUMAB
    D.3.9.1CAS number 477202-00-9
    D.3.9.4EV Substance CodeSUB29397
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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) Yes
    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 Yes
    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
    Metastatic malignant melanoma
    Metastasiertes malignes Melanom
    E.1.1.1Medical condition in easily understood language
    Skin cancer with bone metastases
    Hautkrebs mit Knochenmetastatsen
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10025671
    E.1.2Term Malignant melanoma stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10025650
    E.1.2Term Malignant melanoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10027480
    E.1.2Term Metastatic malignant melanoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    This phase IV study aims to investigate possible immunologic and biologic effects of the concurrent administration of PD-1 blocking antibodies and denosumab as primary endpoint.
    E.2.2Secondary objectives of the trial
    Not applicable.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Translational Research Project
    Translationales Forschungsprojekt.
    E.3Principal inclusion criteria
    • Provision of tumor tissue from metastatic site of disease for biomarker analyses and confirmation by central laboratory. Tumor tissue must be obtained before PD-1 inhibitor therapy (either baseline FFPE sample or archival tissue (ideally obtained after preceding medical tumor therapies).
    • Inoperable metastatic stage IV melanoma arising from a primary cutaneous site or metastatic from an unknown primary site or melanoma of mucosal or uveal origin.
    • Planned therapy with PD-1 blocking antibody (nivolumab or nivolumab + ipilimumab or pembrolizumab) and denosumab as standard of care.
    • Measurable disease according to RECIST1.1 and at least one documented bone metastasis.
    • Age 18 years or above.
    • Written, informed consent.
    • Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
    • Minimum life expectancy of 6 months
    • ECOG performance status of 0-2
    • Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to registration:
    WBC ≥ 2000/μL
    Neutrophils ≥ 1000/μL
    Platelets ≥ 100 x103/μL
    Hemoglobin ≥ 9.0 g/dL
    Serum creatinine ≤ 2.0 x ULN OR
    Creatinine clearance (CrCl) ≥ 35mL/min (using the Cockcroft-Gault formula)
    • AST/ALT ≤ 3 x ULN, in case of liver metastases ≤ 5 x ULN
    Total Bilirubin ≤ 2.0 x ULN (except subjects with Gilbert Syndrome, who may have total bilirubin up to 5 x ULN)
    • Serum calcium or albumin-adjusted serum calcium within normal limits
    • Prior radiotherapy must have been completed prior to study drug administration
    • Negative pregnancy test for female subjects within the week before treatment start and effective contraception for both male and female subjects if the risk of conception exists
    • Bereitstellung von Tumorgewebe einer Metastase des malignen Melanoms für Biomarker –Analysen und zur Bestätigung der Diagnose durch ein zentrales Labor. Das Tumorgewebe muss vor Start der PD-1-Inhibitor-Therapie entnommen werden (entweder neue FFPE Probe zur Baseline oder vorhandene Probe, die idealerweise nach vorherigen Tumortherapien entnommen wurde)
    • Inoperables, metastasiertes Melanom des Stadiums IV, ausgehend von einer kutanen Primärläsion oder von einer Primärläsion unbekannter Lokalisation oder von primärem Schleimhautmelanom oder von primärem Aderhautmelanom
    • Geplante Therapie mit einem PD-1 blockierenden Antikörper (Nivolumab oder Nivolumab + Ipilimumab oder Pembrolizumab) und Denosumab als Therapiestandard
    • Messbare Erkrankung (Vorhandensein mindestens einer nach RECIST 1.1 messbaren Läsion) und mindestens eine dokumentierte Knochenmetastase
    • Alter ≥ 18 Jahre
    • Vorliegen der unterschriebenen Einverständniserklärung
    • Der Patient ist willens und fähig, den Studienvorgaben (z.B. geplante Visiten, Behandlungsplan, Laboruntersuchungen) nachzukommen
    • Lebenserwartung ≥ 6 Monate
    • ECOG Performance Status von 0-2
    • Die Laborwerte aus dem Screening müssen den folgenden Kriterien entsprechen. Die Laboruntersuchungen im Screening sollen innerhalb von 14 Tagen vor der Registrierung erfolgen.
    o Leukozytenzahl (WBC) ≥ 2000/μL
    o Neutrophile ≥ 1000/μL
    o Thrombozyten ≥ 100 x103/μL
    o Hämoglobin ≥ 9.0 g/dL
    o Serumkreatinin ≤ 2.0xULN ODER
    o Kreatinin Clearance ≥ 35mL/min (unter Verwendung der Cockcroft-Gault Formel)
    o AST/ALT ≤ 3 x ULN, bei Lebermetastasen ≤ 5 x ULN
    o Gesamtbilirubin ≤ 2.0 x ULN (ausgenommen Patienten mit Gilbert- Syndrom, für die ein Gesambilirubinwert von bis zu 5 x ULN erlaubt ist)
    o Serumkalzium oder Albumin-korrigiertes Serumkalzium innerhalb üblicher Grenzwerte
    • Eine vorangegangene Radiotherapie muss vor der ersten Gabe der Studientherapie abgeschlossen worden sein
    • Vorliegen eines negativen Schwangerschaftstests innerhalb einer Woche vor der ersten Gabe der Studientherapie für weibliche Patienten. Weibliche und männliche Patienten müssen wirksam verhüten, falls das Risiko einer Empfängnis besteht
    E.4Principal exclusion criteria
    • Prior therapy with CTLA4-inhibitor or PD-1-inhibitor or denosumab for distant metastatic disease. Treatments in the adjuvant setting are allowed in case treatment was discontinued at least 4 weeks before inclusion in this study.
    • No other concurrent medical treatments for metastatic disease such as targeted therapies or chemotherapies are allowed. Treatments in the adjuvant setting are allowed in case treatment was discontinued at least 4 weeks before inclusion in this study.
    • Active CNS metastases requiring local therapy or steroid therapy.
    • Use of any investigational or non-registered product (drug or vaccine) within the past 30 days before study start and during study.
    • Psychiatric or addictive disorders of the patient that may compromise his/her ability to give informed consent or to comply with the trial procedures.
    • Significant dental/oral disease, including prior history or current evidence of osteonecrosis/osteomyelitis of the jaw, or the following: Active dental or jaw condition which requires oral surgery. Non-healed dental/oral surgery. Planned invasive dental procedures for the course of the study.
    • Relevant immune deficiencies or relevant autoimmune disease, as assessed by the investigator.
    • Other malignancies within the past three years which need treatment except basal or squamous skin carcinomas or carcinoma in situ of the cervix
    • Serious cardiac, gastrointestinal, hepatic or pulmonary disease
    • Patients with serious intercurrent illness, requiring hospitalization.
    • Other serious illnesses, e.g., serious infections requiring intravenous antibiotics or bleeding disorders.
    • Hypersensitivity to the active substances of study treatment or to any of the excipients (calcium, vitamin D)
    • Hereditary fructose intolerance
    • Women of childbearing potential: Refusal or inability to use highly effective means of contraception
    • For female patients: the patient is pregnant or lactating or planning to become pregnant within 5 months after the end of the treatment.
    • Vorangegangene Therapie mit einem CTLA4-Inhibitor oder einem PD-1-Inhibitor oder Denosumab für das fernmetastasierte Melanom. Behandlungen im adjuvanten Setting sind erlaubt, sofern die Behandlung mindestens 4 Wochen vor Studieneinschluss beendet wurde.
    • Gleichzeitige medizinische Behandlung des metastasierten Melanoms mit einer zielgerichteten Therapie oder mit einer Chemotherapie. Behandlungen im adjuvanten Setting sind erlaubt, sofern die Behandlung mindestens 4 Wochen vor Studieneinschluss beendet wurde.
    • Aktive ZNS Metastasen, die eine lokale Behandlung oder Steroidtherapie erfordern.
    • Behandlung mit einer Prüfsubstanz oder einem nicht-zugelassenem Produkt (Arzneimittel oder Impfstoff) innerhalb von 30 Tagen vor Studieneinschluss und während der Studienteilnahme.
    • Psychiatrische Erkrankungen oder Suchterkrankungen, durch die die Fähigkeit der Patientin/des Patienten der Studienteilnahme zuzustimmen oder die Studienvorgaben einzuhalten, beeinträchtigt wird.
    • Signifikante zahnmedizinische/orale Erkrankung, inklusive
    o der Vorgeschichte oder des aktuellen Vorliegens einer Osteonekrose/einer Osteomyelitis des Kieferknochens
    o Aktive zahnmedizinische Erkrankung oder Kiefererkrankung, die einer Operation bedarf
    o Nicht-ausgeheilte zahnmedizinische/dentale Operation
    o Geplanter invasiver zahnmedizinischer Eingriff für den Zeitraum der Studienteilnahme
    • Relevante Immundefizienz oder relevante Autoimmunerkrankung
    • Andere behandlungsbedürftige bösartige Tumorerkrankungen innerhalb der letzten drei Jahre, ausgenommen Basalzellkarzinom, Plattenepithelkarzinom der Haut oder Carcinoma in situ des Gebärmutterhalses
    • Schwere Herzerkrankung, schwere gastrointestinale Erkrankung, schwere Lungenerkrankung
    • Patienten mit schwerer interkurrenter Erkrankung, die eine Hospitalisierung notwendig macht
    • Andere schwere Erkrankung, z.B. schwere Infektionen für die eine intravenöse Antibiotikatherapie erforderlich ist oder Blutgerinnungsstörungen
    • Überempfindlichkeit gegenüber den in der Studie angewendeten Wirkstoffen, gegenüber Hilfsstoffen der Studienmedikation sowie gegenüber ergänzender Medikation (Kalzium, Vitamin D)
    • Erbliche Fruktoseintoleranz
    • Für Frauen im gebärfähigen Alter: Weigerung oder Unfähigkeit, hochwirksame Methoden zur Empfängnisverhütung anzuwenden
    • Schwangere, laktierende oder stillende Patientinnen, sowie Patientinnen die planen, innerhalb von 5 Monaten nach Therapieende schwanger zu werden
    E.5 End points
    E.5.1Primary end point(s)
    1) Dynamic changes of the numbers of central memory, effector memory and/or effector T-cells in the circulating blood (based on expression of CD45RA, CD45RO, CCR7, CD62L, and TCF-1)
    2) Dynamic changes of the numbers of cytokine and chemokine present in circulating blood.
    1) Dynamische Änderungen in der Anzahl von zentralen Gedächtnis-T-Zellen, Effektor-Gedächtnis-T-Zellen und/oder Effektor-T-Zellen im zirkulierenden Blut (basierend auf der Expression von CD45R, CD45RO, CCR7, CD62L undTCF-1)
    2) Dynamische Änderungen in der Anzahl von Cytokinen und Chemokinen im zirkulierenden Blut

    E.5.1.1Timepoint(s) of evaluation of this end point
    Variables will be determined at baseline, and after 4, 12 and 24 weeks of therapy.
    Die Variablen werden vor Beginn der Studientherapie (Baseline) und 4, 12 und 24 Wochen nach Beginn der Studientherapie bestimmt.
    E.5.2Secondary end point(s)
    • Safety
    Occurrence of adverse events as assessed by NCI CTC-AE criteria version 5.0
    • Efficacy

    • Sicherheit
    Auftreten unerwünschter Ereignisse (die Bestimmung erfolgt gemäß den NCI CTC-AE Kriterien Version 5.0)
    • Wirksamkeit

    E.5.2.1Timepoint(s) of evaluation of this end point
    1) Overall response rate at 12 and 24 weeks as determined by RECIST 1.1 criteria
    2) Response rate of bone metastases after 12 and 24 weeks of treatment (size and number) as determined by RECIST 1.1 and bone scans
    1) Allgemeine Ansprechrate nach 12 und 24 Wochen (die Bestimmung erfolgt gemäß den RECIST 1.1 Kriterien)
    2) Ansprechrate der Knochenmetastasen nach 12 und 24 Wochen (Größe und Anzahl) (die Bestimmung erfolgt gemäß den RECIST 1.1 Kriterien und Knochen Scans)
    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 Yes
    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 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) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    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 concerned4
    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
    Last patient last visit (LPLV)
    Letzter Besuch des letzten Patienten (LPLV)
    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 months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    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: 10
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state20
    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)
    Following the end of treatment evaluation or the end of study for any other cause, patients will be treated and followed according to the guidelines of the German Cancer Society.
    Nach dem Ende der Behandlung im Rahmen der Studie oder nach dem Ende der Studie für welchen Grund auch immer, werden die Patienten nach den Leitlinien der Deutschen Krebsgesellschaft weiter behandelt oder in Nachsorge übernommen .
    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 Decision2018-09-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-10-22
    P. End of Trial
    P.End of Trial StatusOngoing
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