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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35510   clinical trials with a EudraCT protocol, of which   5839   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).
     
    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:2014-001286-28
    Sponsor's Protocol Code Number:CA209172
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-08-01
    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 number2014-001286-28
    A.3Full title of the trial
    A Single-Arm, Open-Label, Multicenter Clinical Trial with Nivolumab (BMS936558) for Subjects with Histologically Confirmed Stage III
    (unresectable) or Stage IV Melanoma Progressing After Prior Treatment
    Containing an Anti-CTLA-4 Monoclonal Antibody
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A multicenter clinical study with Nivolumab for subjects with confirmed stage III or stage IV melanoma after treament with an Anti-CTLA-4 antibody.
    A.4.1Sponsor's protocol code numberCA209172
    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 SponsorBristol-Myers Squibb International Corporation
    B.1.3.4CountryBelgium
    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 supportBristol-Myers Squibb International Corporation
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBristol-Myers Squibb International Corporation
    B.5.2Functional name of contact pointGCT-SU
    B.5.3 Address:
    B.5.3.1Street AddressParc de l'Alliance - Avenue de Finlande, 4
    B.5.3.2Town/ cityBraine-l'Alleud
    B.5.3.3Post code1420
    B.5.3.4CountryBelgium
    B.5.6E-mailclinical.trials@bms.com
    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
    Histologically Confirmed Stage III (unresectable) or Stage IV Melanoma
    E.1.1.1Medical condition in easily understood language
    Melanoma
    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 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 20.0
    E.1.2Level PT
    E.1.2Classification code 10025670
    E.1.2Term Malignant melanoma stage III
    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
    The primary objective of this trial are:
    - To determine the incidence of high-grade (CTCAE v4.0 Grade 3 or higher), treatment related, select adverse events in patients with histologically confirmed stage III (unresectable) or stage IV melanoma and progression after prior treatment containing an anti-CTLA-4 monoclonal antibody.
    E.2.2Secondary objectives of the trial
    The secondary objectives:
    - To determine the incidence and to characterize the outcome of all highgrade (CTCAE v4.0 Grade 3 or higher), select adverse events in patients
    with histologically confirmed stage III (unresectable) or stage IV
    melanoma and progression after prior treatment containing an antiCTLA-4
    antibody, treated with nivolumab monotherapy.
    - To estimate OS in all treated patients
    - To estimate Investigator-assessed objective response rate (ORR)
    Exploratory objectives: Refer to study protocol
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed Written Informed Consent
    a) Patients must have signed and dated an IRB/IEC approved written
    informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
    b) Patients must be willing and able to comply with scheduled visits,
    treatment schedule, laboratory tests, and other requirements of the
    study.
    2. Target Population
    a) Patients with progression after prior treatment containing an antiCTLA-4
    monoclonal antibody (Cohorts 1 and 2):
    i) Patients with histologically confirmed malignant melanoma
    ii) Eastern Cooperative Oncology Group (ECOG) PS:
    (1) PS 0 to 1 (Cohort 1)
    (2) PS 2 (Cohort 2; a minimum of 50 patients and a maximum of 185;
    clinical risk benefit ratio of Cohort 2 will be monitored by the Scientific
    Steering Committee)
    iii) Previously treated unresectable stage III or stage IV melanoma as
    per the American Joint Committee on Cancer 2010 Guidelines36
    regardless of BRAF mutation status
    iv) Patients must have experienced disease progression or recurrence
    after prior treatment containing an anti-CTLA-4 monoclonal antibody
    v) Prior treatment with chemotherapy, interferon (adjuvant setting), IL2,
    BRAF/MEK inhibitors for patients with known BRAF mutations, MEK
    inhibitors for NRAS mutations, and cKIT inhibitor patients with known
    cKIT mutations are allowed
    vi) Patients with CNS metastases:
    (1) Patients are eligible if CNS metastases are treated and patients are
    neurologically returned to baseline (except for residual signs or
    symptoms related to the CNS treatment) for at least 2 weeks prior to
    enrollment. In addition, patients must be either off corticosteroids or on
    a stable or decreasing dose 10 mg daily prednisone (or equivalent)
    OR
    (2) Patients are eligible if they have previously untreated CNS
    metastases and are
    neurologically asymptomatic. In addition, patients must be either off
    corticosteroids or on a stable or decreasing dose of 10 mg daily
    prednisone (or equivalent)
    OR
    (3) Patients with additional leptomeningeal metastases are eligible if
    they are treated and neurologically returned to baseline (except for
    residual signs or symptoms related to the CNS treatment) for at least 2
    weeks prior to enrollment and have a life expectancy of at least 3
    months. In addition, patients must be either off corticosteroids or on a
    stable or decrease dose 10 mg daily prednisone (or equivalent)
    vii)Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or
    growth factor
    given to control the cancer) must have been completed at least 4 weeks
    before study drug administration, and all adverse events have either
    returned to baseline or have been stabilized
    viii) Prior palliative radiotherapy must have been completed at least 2
    weeks prior to study drug administration
    ix) Prior targeted therapy must have been completed at least 2 weeks
    prior to study drug administration
    x) Prior anti-CTLA-4 therapy must have been completed at least 4 weeks
    before study drug administration
    xi) Prior radiotherapy or radiosurgery must have be completed at least 2
    weeks prior to the first dose of study drug
    xii)Primary uveal (minimum of 30 patients) and mucosal melanoma are
    allowed
    xiii) Screening laboratory values must meet the following criteria prior
    to commencement of treatment:
    (1) WBCs ≥ 2000/μL
    (2) Neutrophils ≥1500/μL
    (3) Platelets ≥ 100 x 10³/μL
    (4) Hemoglobin ≥ 9.0 g/dL
    (5) Serum creatinine of ≤ 1.5 X ULN or creatinine clearance > 40
    mL/minute (using Cockcroft/Gault formula)
    (a) Female CrCl= [(140- age in years) x weight in kg x 0.85) ÷(72 x
    serum creatinine in mg/ dL)]
    (b) Male CrCl= [(140- age in years) x weight in kg x 1.00) ÷(72 x serum
    creatinine in mg/ dL)]
    (6) AST ≤ 3 X ULN
    (7) ALT ≤ 3 X ULN
    (8) Total bilirubin ≤ 1.5x ULN (except patients with Gilbert Syndrome
    who must have total bilirubin < 3.0 mg/dL)
    xiv) Patients with a known history of Grades 3-4 adverse reactions
    during anti-CTLA-4 therapy will be allowed to participate if all toxicities
    have resolved to Grade 1 (NCI CTCAE version 4) or baseline before
    administration of nivolumab (minimum of 40 patients)
    xv) Patients must have evaluable disease by CT or MRI per RECIST 1.1
    criteria (radiographic tumor assessment performed within 6 weeks of
    first dose of study drug)
    or clinically apparent disease that the investigator can follow for
    response.
    xvi) Patient Re-enrollment: This study permits the re-enrollment of a
    subject that has discontinued the study as a pre-treatment failure (ie, subject has not been treated). If re-enrolled, the subject must be re-consented.
    For Other Inclusion Criteria please refer to Protocol
    E.4Principal exclusion criteria
    1. Target Disease Exceptions
    a) As of Amendment 02, this criterion is no longer applicable.
    b) Patients with untreated, symptomatic CNS metastases are excluded
    2. Medical History and Concurrent Diseases
    a) As of Amendment 03, this criterion is not applicable.
    b) Patients with a condition requiring systemic treatment with either
    corticosteroids (>10 mg daily prednisone equivalent) or other
    immunosuppressive medications within 14 days of study drug
    administration. Inhaled or topical steroids and adrenal replacement
    steroid doses > 10 mg daily prednisone equivalent are permitted in the
    absence of active autoimmune disease.
    c) Patients with previous malignancies (except non-melanoma skin
    cancers, in situ bladder cancer, gastric or colon cancers, cervical
    cancers/dysplasia or breast carcinoma in situ) are excluded unless a
    complete remission was achieved at least 2 years prior to study entry
    and no additional therapy is required or anticipated to be required
    during the study period
    d) Any serious or uncontrolled medical disorder or active infection that,
    in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy
    e) Any treatment in a BMS-sponsored, interventional nivolumab trial or
    ipilimumab trial
    f) Known drug or alcohol abuse
    3. Physical and Laboratory Test Findings
    a) Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
    b) Positive test for HIV
    4. Allergies and Adverse Drug Reaction
    a) History of severe hypersensitivity reactions to other monoclonal
    antibodies
    b) History of allergy or intolerance (unacceptable adverse event) to
    study drug components or Polysorbate-80-containing infusions.
    c) As of Amendment 02, this criterion is no longer applicable.
    5. Sex and Reproductive Status
    a) WOCBP who are pregnant or breastfeeding
    b) Women with a positive pregnancy test at enrollment or prior to
    administration of study medication
    c) Women treated with ORAL hormone replacement therapy (HRT) are to
    be excluded unless the oral replacement therapy was stopped by investigator's discretion at least 4 weeks prior to screening and was changed to other contraception method.
    6. As of Amendment 02, this criterion is no longer applicable
    7. Other Exclusion Criteria
    a) Prisoners or subjects who are involuntarily incarcerated
    b) Subjects who are compulsorily detained for treatment of either a
    psychiatric or physical (eg, infectious disease) illness
    Eligibility criteria for this study have been carefully considered to ensure
    the safety of the study subjects and that the results of the study can be
    used. It is imperative that subjects fully meet all eligibility criteria.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the incidence for high-grade (CTCAE v4.0 Grade
    3 or higher), treatment-related, select adverse events.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The analysis of primary, secondary (excluding ORR), and exploratory
    endpoints will be reported for the full safety analysis set and by cohorts
    based on ECOG PS. ORR will be reported for the response evaluable
    analysis set and by PS. OS and ORR will be further presented by initial
    investigator-assessed objective response under treatment with an antiCTLA-4 monoclonal antibody.

    Additional details regarding statistical analysis performed in the study are provided in the Statistical Analysis Plan (SAP), which will be finalized before data base lock.
    E.5.2Secondary end point(s)
    The secondary endpoints include:
     - Incidence of all high-grade (Grades 3 and higher), select adverse
    events
     - Median time to onset and median time to resolution (Grades 3-4) of
    select adverse events
     - OS
     - Investigator-assessed ORR
    The exploratory endpoints include:
     - Safety and tolerability will be measured by the incidence of all
    adverse events, serious adverse events, deaths, and laboratory
    abnormalities. Adverse event assessments and laboratory tests will be performed at baseline and continuously throughout the study at the
    beginning of each subsequent cycle.
     - Investigator-assessed ORR
     - OS
     - Quality of Life as mean and change from baseline in domain scores
    and health status index based on EORTC QLQ-C30 and EQ-5D-3L of the full
    safety analysis set
    E.5.2.1Timepoint(s) of evaluation of this end point
    The analysis of primary, secondary (excluding ORR), and exploratory
    endpoints will be reported for the full safety analysis set and by cohorts
    based on ECOG PS. ORR will be reported for the response evaluable
    analysis set and by PS. OS and ORR will be further presented by initial
    investigator-assessed objective response under treatment with an antiCTLA-4 monoclonal antibody.
    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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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 concerned26
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA210
    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
    Austria
    Belgium
    Czech Republic
    Denmark
    Finland
    Germany
    Greece
    Hungary
    Ireland
    Italy
    Netherlands
    Norway
    Poland
    Portugal
    Romania
    Russian Federation
    Spain
    Sweden
    Switzerland
    United Kingdom
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    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 years4
    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: 520
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 400
    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 state400
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 800
    F.4.2.2In the whole clinical trial 920
    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)
    Normal standard of care.
    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 Decision2014-09-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-11-05
    P. End of Trial
    P.End of Trial StatusCompleted
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA