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   43845   clinical trials with a EudraCT protocol, of which   7282   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:2014-005097-11
    Sponsor's Protocol Code Number:ETOP6-14
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-05-12
    Trial results View 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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2014-005097-11
    A.3Full title of the trial
    A phase II trial evaluating the safety and efficacy of the addition of concurrent anti-PD-1 nivolumab to standard first-line chemotherapy and radiotherapy in locally advanced stage IIIA/B Non-Small Cell Lung Carcinoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Trial to evaluate how severe the side effects are and how well the addition of Nivolumab to standard treatment works in patients with advanced NSCLC.
    A.3.2Name or abbreviated title of the trial where available
    NICOLAS
    NICOLAS
    A.4.1Sponsor's protocol code numberETOP6-14
    A.5.4Other Identifiers
    Name:BMS numberNumber:CA209-208
    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 SponsorETOP (European Thoracic Oncology Platform)
    B.1.3.4CountrySwitzerland
    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 supportBristol-Myers Squibb
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationETOP
    B.5.2Functional name of contact pointETOP Coordinating Office
    B.5.3 Address:
    B.5.3.1Street AddressEffingerstrasse 40
    B.5.3.2Town/ cityBern
    B.5.3.3Post code3008
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+4131511 94 00
    B.5.5Fax number+4131389 93 92
    B.5.6E-mailNICOLAS@etop-eu.org
    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.3.4Pharmaceutical 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.3.9.3Other descriptive nameBMS-936558
    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.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
    locally advanced stage IIIA/B NSCLC
    E.1.1.1Medical condition in easily understood language
    A type of lung cancer called "non small cell lung cancer (NSCLC)" that has spread locally in the area of the lung, but not to distant organs and tissues
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10029520
    E.1.2Term Non-small cell lung cancer stage IIIA
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10029521
    E.1.2Term Non-small cell lung cancer stage IIIB
    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
    To assess the safety and efficacy of the concurrent nivolumab administration with standard fist-line chemotherapy and radiotherapy in locally advanced stage IIIA/B NSCLC, as defined by the rate of grade (equal or greater than) 3 pneumonitis (CTCAE V4.0) 6 months post-radiotherapy and, if safety is proven, to assess the progression-free survival.
    E.2.2Secondary objectives of the trial
    - To evaluate secondary measures of clinical efficacy including time to first pneumonitis of equal or greater than 3, 1-year progression-free survival, objective response rate (ORR), time to treatment failure (TTF) and overall survival (OS).

    - To assess the safety and the tolerability of the Treatment.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Histologically or cytologically confirmed non small cell lung carcinoma
    - Locally advanced stage IIIA or III B (T0-3 N2-3 or T4N0-3 M0) NSCLC, according to 7th TNM classification.
    Within 35 days before beginning of first platinum-based chemotherapy cycle:
    - Nodal status N2 or N3 must be proven (by biopsy, EBUS, mediastinoscopy or thoracoscopy) except for overt cT4 disease.
    - Whole body FDG-PET CT plus contrast enhanced CT of thorax / upper abdomen (from top of thorax until adrenal glands, and full liver and kidney included) in addition to or in combination with PET.
    - brain MRI (preferred) or high-quality brain CT with intravenous contrast at the time of staging mandatory
    within 28 days before enrolment.
    - Measurable disease (according to RECIST v1.1 criteria)
    - Age: equal or greater than 18 years
    - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (see Table 1)
    - Life expectancy > 3 months
    - Previous delivery of a maximum of one 3-weekly cycle of platinum-based chemotherapy
    - All AEs from previous therapies (including the first chemotherapy cycle in the context of this trial) resolved to grade <2 (except fatigue, alopecia, nausea, lack of appetite and peripheral neuropathy).
    - Adequate haematological function:
    - WBC: equal or greater than 2000/microL
    - haemoglobin: equal or greater than 9 g/dL
    - neutrophil Count: equal or greater than 1×109/L
    - platelet Count: equal or greater than 100 × 109/L
    - Adequate liver function:
    - Total Bilirubin: equal or smaller than 2 x ULN (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dl)
    - ALT: equal or smaller than 3 × ULN
    - alkaline phosphatase equal or smaller than 5 x ULN.
    - Adequate renal function: Calculated creatinine clearance ? 30 ml/min (according to Cockroft-Gault, see 10.2)
    - equal or greater than 60ml/min for patient receiving cisplatin
    - equal or greater than 30ml/min for patient receiving carboplatin
    - Pulmonary function FEV1 of 1.0 l or > 40% predicted value and DLCO > 30% predicted value
    - Patient capable of proper therapeutic compliance, and accessible to correct follow-up.
    - Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before trial enrolment. The test must be repeated within 24 hours before beginning nivolumab treatment and then before every 2nd nivolumab administration. Pregnancy tests should be repeated at approximately 30 days and approximately 70 days after nivolumab treatment stops
    - Written Informed Consent (IC) for trial treatment must be signed and dated by the patient and the investigator prior to any trial-related evalutation and/or intervention.
    E.4Principal exclusion criteria
    - Patient with mixed small-cell and non-small-cell histologic features
    - Patient with pleural or pericardial effusions proven to be malignant
    - Prior chemotherapy, radiotherapy or molecular targeted therapy for NSCLC (with the exception of one cycle of chemotherapy given prior to enrolment into this trial, see 7.1.7)
    - Patient with an active, known or suspected autoimmune disease. Patients are permitted to enrol 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.
    - Patient who has had in the past 3 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast.
    - Patient with other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient?s capacity to participate in the trial..
    - Ongoing clinically serious infections requiring systemic antibiotic or antiviral, antimicrobial, antifungal therapy.
    - Known or suspected hypersensitivity to nivolumab or any of its excipients
    - History of severe hypersensitivity reaction to any monoclonal antibody
    - Substance abuse, medical, psychological or social conditions that may interfere with the patient`s participation in the trial or evaluation of the trial results.
    - Established pathological diagnosis of underlying interstitial lung disease or pulmonary fibrosis
    - Women who are pregnant or in the period of lactation
    - Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method (see section 10.8) during the trial treatment and for a period of at least 7 months (male participants) and 5 months (female participants) following the last administration of nivolumab.
    - Patients receiving any concurrent anticancer systemic therapy
    - HIV, active Hepatitis B or Hepatitis C infection
    - Previous radiotherapy to the thorax (prior to inclusion), including radiotherapy for breast cancer
    - Planned radiotherapy to lung of mean dose > 20 Gy or V20 > 35 %
    - Patient who received treatment with an investigational drug agent during the 3 weeks before enrolment in the trial
    - Metastatic disease (mandatory assessment of the brain either by MRI or high-quality CT with intravenous contrast at the time of staging as well as systemic PET and CT scan)
    - 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 costimulation or immune checkpoint pathways
    E.5 End points
    E.5.1Primary end point(s)
    Grade equal or greater than 3 pneumonitis (CTCAE V4.0)
    E.5.1.1Timepoint(s) of evaluation of this end point
    It will be used as the primary endpoint for all patients followed for at least 6 months from end of radiotherapy.
    E.5.2Secondary end point(s)
    Key secondary endpoint:
    - 1-Year progression-free survival

    Other secondary endpoints:
    - Time to first grade equal or greater than 3 pneumonitis (TFP*)
    - Objective Response (OR) determined by RECIST v1.1
    - Time to treatment failure (TTF)
    - Overall survival (OS)
    - Adverse events graded according to CTCAE V4.0
    E.5.2.1Timepoint(s) of evaluation of this end point
    -TFP3 is defined as the time from date of enrolment until first documented pneumonitis grade 3.
    -1-year PFS: It is defined as the time without any documented progression or death, if progression is not documented, from date of enrolment until 1 year after enrolment.
    - OR: is defined as best overall response (CR or PR) across all assessment time-points during the period from enrolment to termination of trial treatment or will be evaluated both from date of enrolment and from date of first nivolumab dose.
    - TTF: Time to treatment failure is defined as time from enrolment to discontinuation of treatment for any reason, including disease progression,treatment toxicity,and death.
    - OS: Defined as time from date of enrolment until death from any cause.
    - AEs: during complete trial duration
    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) 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 Yes
    E.8.5.1Number of sites anticipated in the EEA7
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Germany
    Netherlands
    Spain
    Switzerland
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Patient accrual of 42 reg. protocol v1.0 is expected to be completed within 12 months incl.a run-in-period of 6 months. After a run-in period of 3 months for center activation of protcol v3.0, patient accrual (total size=78) is expected to be completed within 7 months. Follow-up will continue until 2 years from start of nivolumab treatment of the last recruited patient. Trial will end with the preparation of the final report, scheduled at 2.5 years after inclusion of the first patient under AM2.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    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: 78
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 78
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 58
    F.4.2.2In the whole clinical trial 78
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-06-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-08-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-03-31
    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-Thu Apr 18 14:11:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA