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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42556   clinical trials with a EudraCT protocol, of which   7007   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
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    Summary
    EudraCT Number:2014-003935-20
    Sponsor's Protocol Code Number:N14MPN
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-01-15
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2014-003935-20
    A.3Full title of the trial
    A single arm phase II study of Nivolumab in patients with progressive malignant pleural mesothelioma: interim biopsy analysis to determine efficacy. Acronym: NivoMes Study
    Eenarmige fase II study met Nivolumab bij patiënten met een progressief maligne pleuraal mesothelioom: tussentijdse analyse door middel van een biopt om de werkzaamheid te bepalen. Acroniem: NivoMes studie.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Nivolumab in patients with progressive malignant pleural mesothelioma: NivoMes
    Nivolumab behandeling bij een progressief maligne pleuraal mesothelioom: NivoMes
    A.4.1Sponsor's protocol code numberN14MPN
    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 SponsorStichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
    B.1.3.4CountryNetherlands
    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 supportStichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationStichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
    B.5.2Functional name of contact pointJ.M.M.F. Quispel-Janssen
    B.5.3 Address:
    B.5.3.1Street AddressPlesmanlaan 121
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1066 CX
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031205122958
    B.5.5Fax number0031205122572
    B.5.6E-mailjm.janssen@nki.nl
    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 nameNivolumab
    D.3.2Product code BMS-936558
    D.3.4Pharmaceutical form Solution for injection/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.3.9.2Current sponsor codeBMS-936558-01
    D.3.9.3Other descriptive nameBMS936558
    D.3.9.4EV Substance CodeSUB32944
    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.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
    A single arm phase II study of Nivolumab in patients with progressive malignant pleural mesothelioma: interim biopsy analysis to determine efficacy. Acronym: NivoMes Study
    Eenarmige fase II study met Nivolumab bij patiënten met een progressief maligne pleuraal mesothelioom: tussentijdse analyse door middel van een biopt om de werkzaamheid te bepalen. Acroniem: NivoMes studie.
    E.1.1.1Medical condition in easily understood language
    Nivolumab in patients with progressive malignant pleural mesothelioma: NivoMes
    Nivolumab behandeling bij een progressief maligne pleuraal mesothelioom: NivoMes
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10027408
    E.1.2Term Mesothelioma malignant advanced
    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 determine the DCR (disease control rate) at 12 weeks of nivolumab monotherapy in patients with progressive MPM.

    Het bepalen van de DCR (ziekteaktiviteit) bij 12 weken nivolumab monotherapie bij patiënten met progressieve MPM.

    E.2.2Secondary objectives of the trial
    Secondary Objectives
    • To determine the safety of nivolumab monotherapy in patients with recurrent MPM
    • To determine the PFS, OS and TTP of nivolumab monotherapy
    • To determine the objective response rate (ORR) as defined by the modified RECIST criteria

    Exploratory Objectives
    • To determine the effects of nivolumab on tissue samples with respect to influx of immuno-modulating cells.
    • To determine the PD-L1 status of tumors and other possible biomarkers and explore correlations between biomarkers and anti-tumor activity.
    Secundaire doelstellingen
    • Het bepalen van de veiligheid van nivolumab monotherapie bij patiënten met terugkerende MPM.
    • Het bepalen van de PFS, OS en TTP van nivolumab monotherapie.
    • Het bepalen van de objectieve respons rate (ORR).

    Verkennende doelstellingen
    • Het bepalen van de effecten van nivolumab op tumorweefsel samples met betrekking tot de toestroom van immuun-modulerende cellen.
    • Het bepalen van de PD-L1 status van de tumoren en andere mogelijke biomarkers en het verkennen van de correlaties tussen de biomarkers en anti-tumor aktiviteit.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Patients with proven malignant pleural mesothelioma, who have progressive disease after chemotherapy in first or second line.
    • Patients with histological or cytological diagnosed malignant pleural mesothelioma and age >18 years.
    • Medically suitable for limited surgical intervention (pleural biopsies up to limited pleurectomy).
    • Not considered candidates for trimodality treatment (as part of a study).
    • Measurable or evaluable disease (see tumor response assessment).
    • Ability to understand the study and give signed informed consent prior to beginning of protocol specific procedures including the approval of a second thoracoscopy or transthoracic pleural biopsy after the third course.
    • Radiotherapy is allowed when this is given for palliation of painful sites, the interval is > 12 weeks, not more than 1/3 of the bone marrow capacity or all tumor is within the irradiation field.
    • WHO performance status 0 or 1.
    • Adequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:
    • Hematology: Neutrophil count ≥ 1.5 x 109/l, Platelets ≥ 150 x 109/l, Hemoglobin ≥ 6,0 mmol/l.
    • Chemistry: Total serum bilirubin within the upper normal limits; ASAT and ALAT ≤ 2.5 times the upper limits of normal (ULN), AP (alkaline phosphatases) < 5x ULN (unless bone metastases are present in the absence of any liver disease).
    • Patiënten met bewezen maligne mesothelioom van de pleura, die progressieve ziekte hebben na eerste- of tweedelijns chemotherapie.
    • Patiënten met histologische of cytologische bewezen maligne mesothelioom van de pleura en leeftijd > 18 jaar.
    • Medisch geschikt voor beperkte chirurgische ingreep (pleurale biopsieën tot beperkte pleurectomie).
    • Niet beschouwd als kandidaten voor trimodality behandeling (als onderdeel van een studie).
    • Meetbare of evalueerbare ziekte (zie tumorrespons beoordeling).
    • Mogelijkheid om de studie te begrijpen en informed consent te ondertekenen vóórdat er met protocol specifieke procedures wordt gestart met inbegrip van de goedkeuring van een tweede thoracoscopie of transthoracale pleurale biopsie na de derde kuur.
    • Radiotherapie is toegestaan wanneer dit wordt gegeven voor palliatie van pijnlijke sites, het interval > 12 weken is, niet meer dan 1/3 van de capaciteit van het beenmerg of alle tumor zich in het bestralingsveld bevindt.
    • WHO performance status 0-1
    • Adequaat orgaan functioneren zoals blijkt uit de volgende perifere bloedwaarden of serum chemie voor studie start:
    • Hematologie: Neutrofielen ≥ 1.5 x 109/l, Bloedplaatjes ≥ 150 x 109/l, Hemoglobine ≥ 6,0 mmol/l.
    • Chemie: Total serum bilirubin binnen de normale bovengrens; ASAT and ALAT ≤ 2.5 x ULN, AP (alkaline phosphatases) < 5x ULN (tenzij er botmetastases aanwezig zijn in de afwezigheid van elke leverziekte).
    E.4Principal exclusion criteria
    • Active uncontrolled infection, severe cardiac dysfunction or uncorrectable bleeding tendency.
    • Inability to perform biopsies of the pleural lesions.
    • Symptomatic peripheral neuropathy ≥ grade 2 according to NCI CTC, version 4.0.
    • Presence of symptomatic CNS metastases.
    • Unstable peptic ulcer, unstable diabetes mellitus or other serious disabling condition.
    • Impaired renal function: creatinine clearance less than 50ml/min.
    • Concomitant administration to any other experimental drugs under investigation.
    • Patients are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
    • Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immuno-suppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
    • Patients are excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
    • Actieve ongecontroleerde infectie, ernstige cardiale dysfunctie of niet corrigeerbare bloedingsneiging.
    • Onvermogen om bioptin van pleurale lesies te nemen.
    • Symptomatische perifere neuropathie ≥ graad 2 volgens NCI CTC, versie 4.0.
    • Aanwezigheid van symptomatische hersenmetastasen.
    • Instabiele maagzweer, instabiele diabetes mellitus of andere ernstige invaliderende aandoening.
    • Verminderde nierfunctie: creatinine klaring van minder dan 50ml/min.
    • Gelijktijdige toediening van elk ander experimenteel middel dat onderzocht wordt.
    • Patiënten mogen niet deelnemen als zij een actieve, bekende of vermoedelijke auto-immuun ziekte hebben. Patiënten mogen wel deelnemen als zij de volgende aandoeningen hebben: vitiligo; type I diabetes mellitus; residuele hypothyreodie die te wijten is aan een auto-immuun aandoening waarbij alleen hormoon vervanging wordt gegeven; psoriasis, die geen systemische behandeling vereist; of condities, die niet verwacht worden terug te keren in de afwezigheid van een externe trigger.
    • Patiënten mogen niet deelnemen als zij een aandoening hebben waarvoor systemische behandeling met corticosteroiden (>10mg dagelijks prednison equivalenten) of andere immuun-onderdrukkende medicijnen binnen 14 dagen voor inname van de studiemedicatie vereist zijn. Inhalatie of topische steroiden en een dagelijkse dosis prednison < 10 mg of equivalent hiervan voor suppletie bij bijnierinsufficiëntie, zijn toegestaan als er geen actieve auto-immuunziekte aanwezig is.
    • Patiënten mogen niet deelnemen als zij eerder behandeld zijn met anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antilichaam, of elke andere antilichaam of medicijnen die specifiek gericht zijn op T-cel co-stimulatie of 'immuun checkpoint pathways'.
    E.5 End points
    E.5.1Primary end point(s)
    DCR at 12 weeks.
    DCR (disease control rate) bij 12 weken
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks
    12 weken
    E.5.2Secondary end point(s)
    Safety, PFS, OS, TTP, ORR
    Veiligheid, progressievrije overleving, algehele overleving, tijd tot progressie, algehele respons rate.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Safety: 2 weekly during treatment, thereafter every 6 weekly until week 24. Thereafter 8 weekly.
    PFS, TTP and ORR: 6 weekly until week 24. Thereafter 8 weekly
    OS: 8 weekly
    Veiligheid: elke 2 weken tijdens de behandeling, daarna elke 6 weken tot week 24. Daarna elke 8 weken.
    Progressievrije overleving, tijd tot progressie en algehele respons rate: elke 6 weken tot week 24. Daarna elke 8 weken.
    Algehele overleving: elke 8 weken
    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 Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled 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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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
    LVLS
    Laatste visite van de laatste patient
    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 months0
    E.8.9.1In the Member State concerned 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: 16
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 17
    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 state33
    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)
    Once patients have been discontinued from study treatment, other treatment options will be at the discretion of the investigator
    Zodra patienten de studiebehandeling hebben beeindigd, zullen andere behandelingsopties besproken worden door de onderzoeker
    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 Decision2015-01-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-07-02
    P. End of Trial
    P.End of Trial StatusOngoing
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