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    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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).

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    Summary
    EudraCT Number:2007-000416-91
    Sponsor's Protocol Code Number:CA186001
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-06-11
    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 ConcernedFrance - ANSM
    A.2EudraCT number2007-000416-91
    A.3Full title of the trial
    A Phase I/II, Ascending, Multi-Dose Study of BMS-663513, An Agonistic Anti-CD137
    Monoclonal Antibody, Administered Every Three Weeks to Patients with Metastatic or
    Locally Advanced Solid Malignancies.

    Revised Protocol Number 07, incorporating Amendments 01, 02, 03, 04, 05, 06, 07 and Administrative Letter Dated 10-Mar-2006.
    A.4.1Sponsor's protocol code numberCA186001
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameAnti-CD137
    D.3.2Product code BMS-663513
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeBMS-663513
    D.3.9.3Other descriptive nameAnti-CD137
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typeHuman monoclonal antibody (IgG4) produced in CHO cells
    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
    Patients with Metastatic or Locally Advanced Solid Malignancies
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10025650
    E.1.2Term Malignant melanoma
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10038395
    E.1.2Term Renal carcinoma
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10033131
    E.1.2Term Ovarian carcinoma
    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 tolerability of BMS-663513 in the range of 0.3 mg/kg to
    15 mg/kg administered once every 3 weeks to patients with metastatic or locally advanced solid malignancies in the dose escalation portion of the study. To estimate the reversible Grade 3-4 toxicity rate in the expanded dose cohorts of melanoma, ovarian and renal carcinoma patients at each of the 3 selected doses (1, 3 and 10 mg/kg).
    E.2.2Secondary objectives of the trial
    •Assess the PK of BMS-663513
    •Assess BMS-663513 dose & biologic effect relationships using:
    −Flow cytometry to quantitate subsets of immune cells (CD3, CD4, CD8, CD19, &
    CD16/56)
    −Flow cytometry to measure subsets of T cells (activated, memory)
    −QRT-PCR to measure changes in RNA expression in peripheral blood
    −ELISA to measure changes in levels of cytokines &/or other biomolecules
    •Screen for anti-tumor activity of single agent BMS-663513
    •Assess the effect of BMS-663513 on immune response to non-cancer vaccines (influenza, tetanus, pneumoccocal)
    •Assess the immunogenic potential of BMS-663513
    •Assess the effect of BMS-663513 on intratumoral immune response pre and post treatment using immunohistochemistry
    •Obtain fresh & paraffin embedded tumor samples, & blood, to identify potential predictive markers of biological response utilizing ribonucleic acid (RNA) profiling, protein profiling, single nucleotide polymorphism (SNP) analysis, & other techniques
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Signed written informed consent

    - Target population
    a) Able to comply with visits/procedures required by the protocol
    b) Life expectancy of at least 3 months
    c) ECOG performance status score 0 - 1 (Protocol Appendix 4).
    d) Patients with histologic or cytologic diagnosis of an advanced solid malignancy
    who have failed, refused or are unable to receive standard treatment.
    NOTE: Patients enrolled after Amendment 7 is IRB approved are limited to:
    • Melanoma (must be anti-CTLA-4 naive),
    • Renal (clear cell) carcinoma, or
    • Epithelial carcinoma arising from the ovary, fallopian tube or peritoneum.
    e) At least 1 site of measurable disease (excluding epithelial carcinoma who must
    have at least 1 site of “evaluable” disease)
    f) A tumor paraffin embedded tissue block or 5 - 15 unstained slides from the tumor
    tissue block (from the primary or a metastatic tumor) must be provided for
    biomarker and predictive marker analyses. Note: If the tumor tissue block or unstained slides are not available or insufficient, additional fresh tumor tissue
    could be collected during the optional pretreatment biopsy to satisfy this criteria
    g) At least 4 weeks must have elapsed since the last chemotherapy, immunotherapy,
    hormonal therapy, radiotherapy or major surgery, & the 1st day of BMS-663513 therapy. At least 6 weeks for nitrosoureas, mitomycin C & liposomal doxorubicin
    h) Toxicities related to prior therapy must either have returned to ≤ Grade 1, baseline or deemed irreversible

    -Age and Sex
    a) Men and women, who are at least 18 years of age.
    − Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche & who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 IU/mL. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an
    intrauterine device or barrier methods (diaphragm, condoms, spermicides) to
    prevent pregnancy or practicing abstinence or where partner is sterile (eg,
    vasectomy), should be considered to be of child bearing potential.
    − WOCBP must have a negative pregnancy test [minimum sensitivity 25 IU/L
    or equivalent units of beta-human chorionic gonadatrophin (βHCG)] within
    72-hours prior to the start of study medication.

    - Physical and laboratory test findings:
    a) Adequate bone marrow function defined as:
    Absolute neutrophil count (ANC) >= 1,500 cells/mm³
    Platelet count >= 100,000 cells/mm³
    Hemoglobin >= 9.0 g/dl
    b) Adequate hepatic function defined as:
    Total bilirubin =< 1.5 times the institutional upper limit of normal (IULN)
    ALT, AST and alkaline phosphatase =< 2.5 times the IULN
    c) Adequate renal function defined as:
    Serum creatinine =< 1.5 times the IULN or
    Calculated creatinine clearance of >= 60 mL/min/1.73m²
    E.4Principal exclusion criteria
    - Sex and Reproductive Status
    a) WOCBP who are unwilling or unable to use an acceptable method to avoid
    pregnancy for the entire study period and for up to 12 weeks after the study.
    b) WOCBP using a prohibited contraceptive method.
    c) Women who are pregnant or breastfeeding.
    d) Women with a positive pregnancy test on enrollment or prior to study drug
    administration.
    e) Sexually active fertile men, whose partners are WOCBP, who are unwilling or
    unable to use an acceptable method of birth control from the time of enrollment
    and for 12 weeks after participation in the study.

    - Medical History and Concurrent Diseases
    a) Active infection or uncontrolled significant acute or chronic medical illness other
    than current cancer that would prohibit safe administration of BMS-663513.
    b) Any concurrent malignancy other than adequately treated basal or squamous cell
    skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix.
    Patients with a previous malignancy but without evidence of disease for >= 5 years
    will be allowed to enter the trial.
    c) History of autoimmune diseases including rheumatoid arthritis, lupus
    erythermatosus, uveitis and autoimmune inflammatory eye disease, psoriasis,
    multiple sclerosis, inflammatory bowel diseases, etc. Type I diabetes mellitus is
    allowed.
    d) Known or suspected human immunodeficiency virus (HIV) positive.
    e) Any current condition requiring the continued use of systemic or topical steroids
    or the use of immunosuppressive agents (eg, cyclosporine and its analog, or
    chemotherapy agents). All corticosteroid use must have been discontinued
    >= 4 weeks prior to Day 1 of treatment.
    f) Active/symptomatic brain metastasis. Patients with signs or symptoms suggestive
    of brain metastasis are not eligible unless brain metastases are ruled out by
    computerized axial tomography (CT) scan or magnetic resonance imaging (MRI).
    Patients with stable brain metastasis and those who were previously treated with
    radiotherapy or surgery must have no current evidence of active/symptomatic
    brain metastasis and are off steroid therapy for at least 4 weeks prior to Day 1 of
    treatment.
    g) Uncontrolled or significant cardiovascular disease including myocardial infarction
    within 6 months, uncontrolled angina, Class III-IV New York Heart Association
    (NYHA) congestive heart failure (Appendix 5) and clinically significant
    ventricular arrhythmias.
    h) Any other sound medical, psychiatric and/or social reason, which in the opinion
    of the principal investigator, would prohibit the understanding of the informed
    consent and/or make the administration of study drug hazardous or obscure the
    interpretation of adverse events.
    i) History of hepatitis B or C, or alcohol induced liver disease.

    - Physical and Laboratory Test Findings
    a) Evidence of organ dysfunction or any clinically significant deviation from normal
    in physical examination, vital signs, ECG or clinical laboratory determinations.
    b) Positive blood screen for hepatitis B surface antigen, or hepatitis C antibody.

    - Allergies and Adverse Drug Reactions
    a) History of allergy to BMS-663513 or related compounds.

    - Prohibited Therapies and/or Medications
    a) Exposure to any investigational products within 4 weeks prior to Day 1 of
    treatment.
    b) Use of any immunosuppressing treatments including corticosteroids,
    cyclosporine, mycophenolate mofetil (CellCept®), chemotherapy, radiation, etc,
    within 4 weeks prior to Day 1 of treatment.

    -Other Exclusion Criteria
    a) Prisoners or patients who are compulsorily detained
    E.5 End points
    E.5.1Primary end point(s)
    • Primary Safety Outcome Measures:
    Safety assessments will be based on medical review of adverse event (AE) reports and the results of vital sign measurements, EKG/ECG, physical examinations, and clinical laboratory tests. AEs will be recorded using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 and the incidence will be tabulated and reviewed for potential significance and clinical importance.

    • Pharmacokinetic Measures:
    PK parameters (Cmax, Cmin, Tmax, AUC(INF), AUC(TAU), T1/2, CLT, Vss, and λx) may be derived from serum concentration versus time for BMS-663513.

    • Efficacy Measures:
    Tumor response will be determined for all patients using a modified form of the WHO criteria. These assessments will be made at week 12 and every 6 weeks thereafter or more frequently if indicated.

    • Pharmacodynamic Measures:
    Exploratory research to assess dose and biologic effect relationships will be assessed by measurement of changes in peripheral T cell subsets using flow cytometry, changes in RNA expression in peripheral blood using QRT-PCR and changes in cytokines or other biomolecules using ELISA. Anti-influenza, anti-pneumoccocal and anti-tetanus antibody titers may be measured 3 to 4 weeks after immunization. Exploratory research to discover predictive markers of response will be performed using RNA profiling, SNP analysis and IHC of tumor tissue.
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    immune response
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3.1Comparator description
    patients will be randomized to receive 1, 3 or 10 mg/kg of BMS-663513 in a 1:1:1 ratio
    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 concerned2
    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 Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    LPLV
    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 months10
    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 months10
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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.4.2 For a multinational trial
    F.4.2.1In the EEA 20
    F.4.2.2In the whole clinical trial 110
    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)
    For patients who have a study related toxicity, a follow up visit will be required every 4 weeks, or more frequent as appropriate, until all study related toxicities have either resolved, returned to baseline, stabilized or are deemed by the investigator to be irreversible.

    Patients will also be followed for efficacy and time to progression or death for up to
    2 years after their last treatment. The first visit should occur approximately 3 months
    after the last dose of protocol therapy.
    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 Decision2007-07-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-07-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2008-12-30
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    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.

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