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    The EU Clinical Trials Register currently displays   36122   clinical trials with a EudraCT protocol, of which   5938   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2008-003533-24
    Sponsor's Protocol Code Number:CA182033
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2009-03-10
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2008-003533-24
    A.3Full title of the trial
    A Randomized, Double-blind, Multi-center Phase III Study of Brivanib versus Sorafenib
    as First-line Treatment in Patients with Advanced Hepatocellular Carcinoma (The BRISK FL Study)

    Pharmacogenetics Blood Sample Amendment 1 (v1.0, dated 10-Dec-2008) //////////

    Estudio fase III aleatorizado, doble ciego, multicéntrico, de brivanib frente a sorafenib como tratamiento de primera línea en pacientes con carcinoma hepatocelular avanzado (Estudio BRISK FL)

    Enmienda sobre muestras de sangre para farmacogenética Número 01 ((v1.0, de fecha 10-Dic-2008)
    A.3.2Name or abbreviated title of the trial where available
    BRISK FL Study
    A.4.1Sponsor's protocol code numberCA182033
    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 nameBrivanib Alaninate
    D.3.2Product code BMS-582664-02
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNBrivanib Alaninate
    D.3.9.1CAS number 649735-63-7
    D.3.9.3Other descriptive nameVEGFR2
    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) 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 No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Nexavar
    D.2.1.1.2Name of the Marketing Authorisation holderBayer HealthCare AG
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/06/364
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Over encapsulated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNSorafenib (as tosylate)
    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) 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 No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule*
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    advanced hepatocellular carcinoma ///////////

    Carcinoma Hepatocelular avanzado
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10019828
    E.1.2Term Hepatocellular carcinoma non-resectable
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the Overall Survival (OS) of brivanib versus sorafenib in subjects with
    advanced HCC who have not received prior systemic treatment.
    E.2.2Secondary objectives of the trial
    ? To compare the time to progression (TTP) (investigator assessed using modified
    RECIST criteria)
    ? To compare the investigator assessed objective response rate (ORR) and disease
    control rate (DCR) using modified RECIST criteria
    ? To determine duration of response, duration of disease control, and time to response (TTR)
    ? To assess the safety profile of brivanib and sorafenib
    ? To explore PK and exposure-response in the study population
    ? To compare time to symptomatic progression
    ? To compare health-related quality of life.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Signed Written Informed Consent
    a) Voluntary signed and dated written informed consent form in accordance with
    regulatory and institutional guidelines obtained before the performance of any
    protocol-related procedures not part of normal patient care.
    2) Target Population
    a) Histologic or cytologic confirmed diagnosis of HCC.
    b) Advanced HCC
    i) disease not eligible for surgical and / or locoregional therapies
    ii) progressive disease after surgical and / or locoregional therapies
    c) Child-Pugh Class A
    d) ECOG performance status 0-1 Life expectancy of at least 12 weeks
    f) Accessible for treatment and follow-up
    g) Locoregional therapy must be completed at least 3 weeks prior to the baseline
    scan; previously treated lesions are not to be selected as target lesions.
    h) At lease one measurable untreated lesion. All subjects must have at least one
    previously un-treated, uni-dimensionally measurable lesion by CT or MRI scan ?
    20mm. Target lesions that are previously un-treated and are uni-dimensionally
    measurable by spiral CT scan to be? 10mm will be permitted.
    i) The lesion can be accurately measured uni-dimensionally according to RECIST criteria
    ii) The lesion has not been previously treated with surgery, radiotherapy, and /or
    locoregional therapy (eg: radiofrequency ablation (RFA), percutaneous ethanol or acetic acid injection (PEI / PAI), transcatheter arterial chemoembolization (TACE) or cryoablation, etc.)
    iii) Bone metastases are not considered measurable lesions.
    3) Physical and Laboratory Test Finding
    a) Adequate hematologic function with absolute neutrophil counts ? 1,500/mm3,
    platelet count ? 60 x 10E9/L, and hemoglobin ? 8.5 g/dL
    b) Adequate hepatic function with serum total bilirubin ? 3 mg/dL, serum albumin
    ? 2.8 g/dL and ALT and AST ? 5 times the institutional upper limits of normal
    c) Amylase and lipase ? 1.5 times the institutional upper limit of normal
    d) Adequate renal function with serum creatinine ? 2.0 mg/dL
    e) International normalized ratio (INR) ? 2.3 or Prothrombin time (PT) ? 6 seconds
    above control
    f) Left ventricular ejection fraction (LVEF) ? 50% as measured by 2-D Echocardiogram
    g) All laboratory test finding should be stable within the range listed in 3a) - 3f)
    without continuous supportive treatment, such as blood transfusion, coagulation
    factors and / or platelet infusion, red / white blood cell growth factor administration, albumin infusion, ursodeoxycholic acid, or drug treatment for lowering liver enzyme / bilirubin, etc.
    4) Age and Sex
    a) Men and women, ages 18 or older
    b) 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 last dose of investigational product in such a manner that the risk of
    pregnancy is minimized.
    E.4Principal exclusion criteria
    1) 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 last dose of
    investigational product.
    b) Women who are pregnant or breastfeeding
    c) Women with a positive pregnancy test on enrollment or prior to investigational
    product administration.
    d) Sexually active fertile men not using effective birth control if their partners are
    WOCBP.
    2) Target Disease Exceptions
    a) Brain metastasis or evidence of leptomeningeal disease
    b) Known fibrolamellar HCC or mixed cholangiocarcinoma and HCC
    c) History of encephalopathy
    d) Ascites
    e) Evidence of portal hypertension with bleeding esophageal or gastric varices
    within the past 2 months
    f) Main portal vein or vena cava thrombosis or occlusion.
    3) Medical History and Concurrent Diseases
    a) Previous or concurrent cancer that is distinct in primary site or histology from
    HCC, except cervical carcinoma in situ, treated basal cell carcinoma, superficial
    bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 5 years prior to
    entry is permitted.
    b) History of active cardiac disease:
    i) Uncontrolled hypertension which defined as systolic blood pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management
    ii) Congestive heart failure NYHA (New York Heart Association) class 3 and 4
    iii) Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction less than 12 months prior to study entry.
    iv) Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
    v) Valvular heart disease ? CTCAE Grade 2
    c) QTc (Fridericia) > 450 msec on two consecutive ECGs. (baseline ECG should be
    repeated if QTc is found to be > 450 msec)
    d) Thrombotic or embolic events within the past 6 months, such as a cerebrovascular
    accident (including transient ischemic attacks), pulmonary embolism
    e) Any other hemorrhage/bleeding event ? CTCAE Grade 3 within 4 weeks except for esophageal or gastric varices
    f) Active infection, less than 7 days after completing systemic antibiotic therapy
    g) Active, untreated hepatitis B
    h) Psychiatric illness/social situations that would limit compliance with study requirements
    i) History of non-healing wounds or ulcers, or bone fractures within 3 months of
    fracture
    j) Major surgical procedure, open biopsy, or significant traumatic injury less than 3
    weeks or those who receive minor surgical procedures (eg core biopsy or fine needle aspiration) within 1 week
    k) History of organ allograft or on an allograft waiting list
    l) Portal-caval shunts
    m) Inability to swallow tablets or untreated malabsorption syndrome
    n) Pre-existing thyroid abnormality with thyroid function that cannot be maintained
    in the normal range with medication
    o) History of human immunodeficiency virus (HIV) infection
    p) Substance abuse, medical, psychological or social conditions that may interfere
    with the patient?s participation in the study or evaluation of the study results.
    q) Any medical condition that is unstable or which could jeopardize the safety of the
    patient and his/her compliance in the study.
    4) Physical and Laboratory Test Findings
    a) Positive pregnancy test
    b) Baseline serum sodium < 130 mmol/L
    c) Baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry)
    5) Allergies and Adverse Drug Reactions
    a) Known or suspected history of allergy to brivanib or sorafenib or any agents given in association with this trial
    6) Prohibited Treatments and/or Therapies
    a) Prior use of any systemic anti-cancer chemotherapy, immunotherapy or molecular
    targeted agents for HCC
    b) Concomitant treatment with rifampin (and its analogues), or St John?s wort
    c) Prior use of systemic investigational agents for HCC
    d) Radiotherapy within 4 weeks prior to start of study drug
    e) Required anticoagulation therapy with an agent such as coumadin, warfarin or
    heparin
    f) Required chronic anti-platelet therapy (aspirin at dose ? 300 mg/day, clopidogrel
    at dose ? 75 mg/day).
    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.
    E.5 End points
    E.5.1Primary end point(s)
    Primary endpoint of this study is overall survival.
    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 Yes
    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 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA39
    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 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
    The study will be closed when the required number of randomized subjects has documented death events.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years3
    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 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 state48
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 252
    F.4.2.2In the whole clinical trial 1800
    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 Decision2009-04-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-04-07
    P. End of Trial
    P.End of Trial StatusOngoing
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