Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2018-004854-12
    Sponsor's Protocol Code Number:N19RER
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-01-28
    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 number2018-004854-12
    A.3Full title of the trial
    An Open-label Single-arm Pharmacokinetic Trial, Investigating the Effect of CYP3A4 inhibitor Ritonavir on the Pharmacokinetics of Erlotinib
    Een open-label, eenarmige studie waarbij er wordt gekeken naar effect van CYP3A4 remmer ritonavir op de farmacokinetiek van erlotinib
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Investigation of the blood levels at a reduced dose of erlotinib with the addition of ritonavir compared to the normal dose of erlotinib
    Onderzoek naar de bloedwaardes bij een verlaagde dosis erlotinib met toevoeging van ritonavir in vergelijking met de normale dosering erlotinib
    A.3.2Name or abbreviated title of the trial where available
    N19RER
    A.4.1Sponsor's protocol code numberN19RER
    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 Leuewenhoek 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 Leuewenhoek Ziekenhuis
    B.5.2Functional name of contact pointDr. N. Steeghs
    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 number0031205192532
    B.5.5Fax number0031205122572
    B.5.6E-mailn.steeghs@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 Yes
    D.2.1.1.1Trade name Tarceva
    D.2.1.1.2Name of the Marketing Authorisation holderRoche
    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 nameErlotinib
    D.3.2Product code L01XE03
    D.3.4Pharmaceutical form 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 INNERLOTINIB
    D.3.9.1CAS number 183321-74-6
    D.3.9.2Current sponsor codeEMEA/H/C/000618
    D.3.9.3Other descriptive nameErlotinib
    D.3.9.4EV Substance CodeSUB16423MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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 Norvir
    D.2.1.1.2Name of the Marketing Authorisation holderAbbott bv
    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 nameRitonavir
    D.3.2Product code J05AE03
    D.3.4Pharmaceutical form 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 INNRITONAVIR
    D.3.9.1CAS number 155213-67-5
    D.3.9.2Current sponsor codeEMEA/H/C/000127
    D.3.9.3Other descriptive nameritonavir
    D.3.9.4EV Substance CodeSUB10342MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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
    Advanced EGFR mutation positive non small cell lung cancer, pancreatic carcinoma, colorectal cancer and biliary cancer
    Gevorderd EGFR mutatie positief niet-kleincellig longkanker, pancreascarcinoom, colorectaal kanker en galwegkanker
    E.1.1.1Medical condition in easily understood language
    non small cell lung cancer, pancreatic carcinoma, colorectal cancer and biliary cancer
    niet-kleincellig longkanker, pancreaskanker, darmkanker en galwegkanker
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    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
    Effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of erlotinib, measured as AUC0-24h, AUCmean, Cmax and Cmin
    Vergelijken farmacokinetiek van erlotinib 150mg en erlotinib 75mg+ ritonavir
    E.2.2Secondary objectives of the trial
    1. Safety of the CYP3A4 moderator ritonavir in combination with erlotinib, which will be measured as the incidence and severity of adverse events with and without ritonavir, according to CTC-AE v4.03.
    2. The correlation between the pharmacokinetics, measured as AUC0-24h, AUCmean, Cmax and Cmin of ritonavir and toxicity according to CTC-AE v4.03
    3. Study the effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of the active metabolite of erlotinib, OSI-420 , measured as AUC0-24h, AUCmean, Cmax and Cmin.
    4. Quantification of ctDNA, determined with Droplet digital PCR (ddPCR)
    -Veiligheid
    -Farmacokinetiek van ritonavir
    -Farmacokinetiek va de actieve metaboliet van erlotinib, OSI-420.
    -Monitoren van de mutatiestatus middels digital droplet polymerase chain reaction (ddPCR)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Patients treated with single agent erlotinib 150mg QD, without disease progression at the first regular response evaluation after treatment initiation or patients who may benefit from erlotinib treatment
    • Age ≥ 18 years
    • Accessible for repeated venipunctures
    • Ability to understand the study and give signed informed consent prior to beginning of protocol specific procedures
    - Patiënten worden behandeld met 150mg erlotinib, zonder progressie op de eerste responsevaluatie na start behandeling of patienten die mogelijk baat hebben bij behandeling met erlotinib.
    - ≥ 18 jaar
    - Mogelijkheid tot herhaalde venapunctie
    - Patiënt moet in staat zijn om de studie te begrijpen en informed consent te geven, voordat er studie specifieke procedures worden gestart.
    E.4Principal exclusion criteria
    • Concomitant use of medication(s) which could influence the pharmacokinetics of erlotinib within 14 days or five half-lives of the drug (whichever is shorter) before start of the study, consisting of (but not limited to) CYP3A4-inhibitors/inductors
    • Active uncontrolled infection or severe cardiac dysfunction (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina)
    • Impaired hepatic function (total bilirubin > ULN or Child-Pugh A, B and C)
    • Woman who are pregnant or breast feeding
    • Progression on erlotinib at the latest regular response evaluation
    • Current smokers or stopped smoking within 7 days before study allocation
    - Co- medicatie die CYP3A4 beïnvloeden.
    - Actieve ongecontroleerde infectie of ernstig hartfalen (zoals NYHA Klasse III of IV cardiale ziekte, myocard
    - Verminderde leverfunctie (totaal bilirubin > ULN or Child-Pugh A, B and C
    - Zwangerschap of borstvoeding
    - Progressie op erlotinib
    - Huidige roker of stoppen met roken binnen 7 dagen voor studie toewijzing

    E.5 End points
    E.5.1Primary end point(s)
    The effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of erlotinib, measured as AUC0-24h, Cmax and Cmin.
    Het effect van ritnonavir op de AUC0-24h, Cmax en Cmin van erlotinib
    E.5.1.1Timepoint(s) of evaluation of this end point
    15 days
    15 dagen
    E.5.2Secondary end point(s)
    1. The incidence and severity of adverse events of co-administration of the highly potent CYP3A4 inhibitor ritonavir, according to CTC-AE v4.03.
    2. To determine the correlation between the ritonavir pharmacokinetics (AUC0-24h, Cmax and Cmin) and the incidence and severity of adverse events.
    3. To Study the effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of the active metabolite of erlotinib OSI-420 , measured as AUC0-24h, Cmax and Cmin.
    4. Quantification of ctDNA, determined with Droplet digital PCR (ddPCR)
    1. Incidentie van (serieuze) bijwerkingen, uitgedrukt volgens CTC-AE v4.03
    2. De correlatie tussen de spiegels van ritonavir en toxiciteit volgens CTC-AE v4.03.
    3. Het effect van ritnonavir op de AUC0-24h, Cmax en Cmin van de actieve metaboliet van erlotinib, OSI-420
    4. Kwantificatie van ctDNA
    E.5.2.1Timepoint(s) of evaluation of this end point
    Not applicable
    Niet van toepassing
    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 No
    E.6.6Pharmacokinetic Yes
    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 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 years0
    E.8.9.1In the Member State concerned months7
    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: 8
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    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 state10
    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
    Geen
    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 Decision2019-01-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-04-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-10-21
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 18:26:18 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA