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   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).

    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:2006-001012-68
    Sponsor's Protocol Code Number:CA182-006
    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:2006-11-30
    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 number2006-001012-68
    A.3Full title of the trial
    A Randomized 2-Arm, Open Label, Phase II Study of BMS-582664, Administered Orally At A Dose of 800 mg Daily or Doxorubicin Administered Intravenously At A Dose of 60 mg/m2 Every 3 Weeks In Patients with Unresectable, Locally Advanced or Metastatic Hepatocellular Carcinoma

    Revised Protocol Number 01, incorporating Amendment 02
    + Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific, version 1.0 dated 29-Apr-06
    A.4.1Sponsor's protocol code numberCA182-006
    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 nameBMS-582664
    D.3.4Pharmaceutical form 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 INNBMS-582664-02
    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 Yes
    D.3.11.13.1Other medicinal product typeSmall molecule
    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 Doxorubicin Hydrochloride 50 mg Powder for Injection
    D.2.1.1.2Name of the Marketing Authorisation holderFaulding Pharmaceuticals Plc
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical form Powder for injection*
    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.3.8INN - Proposed INNDoxorubicin Hydrochloride
    D.3.9.1CAS number 23214-92-8
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Unresectable, advanced or metastatic hepatocellular carcinoma
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8.1
    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 estimate the 6-month progression free survival rate in patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC) with no prior chemotherapy for HCC, treated with 800 mg QD of BMS-582664 orally or with doxorubicin intravenously at a dose of 60 mg/m2 Q 3 weeks.
    E.2.2Secondary objectives of the trial
    • To estimate the difference in 6 month PFS rate in patients treated with BMS-582664 at 800 mg QD with patients treated with 60 mg/m2 of doxorubicin Q3-Weeks
    • To estimate tumor response rate, time to response, duration of response, progression free survival, overall survival, and disease control rate in each arm
    • To assess the safety and tolerability of BMS-582664 versus doxorubicin in this patient population.
    • To obtain samples for population PK of BMS-540215 (the active moiety) in patients with hepatocellular carcinoma treated with BMS-582664.
    • To assess the effects of the BMS-582664 and doxorubicin on pharmacodynamic markers in patients with hepatocellular carcinoma.
    • To obtain blood, paraffin embedded biopsy (if available) and (optional) fresh tumor samples to identify potential predictive markers of biological response

    See protocol section 2.2 for more objectives
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Signed written informed consent

    Target population
    2) Patient with diagnosis of hepatocellular carcinoma meeting the criteria below:
    a) Biopsy-proven HCC (Histology or cytology)
    OR
    b) Radiological evidence of HCC by contrast-enhanced CT scan or contrastenhanced MRI
    AND
    i) Serology positive for Hepatitis B or C
    AND
    ii) Alpha fetoprotein > 400 µg/L
    3) Not appropriate for curative surgical resection.
    4) Subjects who have received local therapy such as surgery, chemoembolization, radiation therapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible, provided that they either have a index lesion which has not been subjected to local therapy and/or the index lesion(s) within the field of the local therapy has shown an increase of ≥ 25% in size. Local therapy must be completed at least 4 weeks prior to the baseline scan.
    5) Measurable disease
    All patients must have at least one previously un-irradiated, bi-dimensionally measurable lesion by CT or magnetic resonance imaging (MRI) scan of ≥ 20 mm. Triphasic spiral CT or MRI scans are preferred when such equipment is available. All CT scans should employ a “hepatoma protocol” image capture technique. The following are not considered measurable lesions:
    a) Lesions seen on colonoscopy examination or barium studies
    b) Ascites
    6) More than 4 weeks since surgery (with the exception of venous port access)
    7) “Cancer for the Liver Italian Program” Score (CLIP) ≤ 3
    a) No evidence of encephalopathy
    8) ECOG performance status of 0, 1, 2
    9) Adequate bone marrow function:
    a) Absolute neutrophil count ≥ 1500/mm3
    b) Platelet count ≥ 80,000/mm3
    c) Hemoglobin ≥ 9 g/dL
    10) Adequate hepatic function:
    a) Total bilirubin ≤ 2.5 mg/dL
    b) AST/ALT ≤ 5 times the upper limit of normal (ULN)
    c) Serum albumin > 2.8 g/dL
    d) PT or INR ≤ 1.8 times ULN
    11) Adequate renal function:
    a) Creatinine ≤ 2.0 mg/dL, OR
    b) Creatinine clearance ≥ 45 mL/min based on Cockcroft formula
    12) Screening blood pressure of < 150/100 mmHg
    13) Left ventricular ejection fraction (LVEF) ≥ 50%

    Age and Sex
    14) Men and women, ages 18 and older.
    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.
    E.4Principal exclusion criteria
    Sex and Reproductive Status
    1) 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.
    2) WOCBP not using an acceptable method of contraception sufficient to prevent pregnancy according to the instructions of the Principal Investigator.
    3) Women who are pregnant or breastfeeding
    4) Women with a positive blood serum pregnancy test on enrollment or prior to study drug administration.

    Target Disease Exceptions
    5) Exclude patients with CLIP score >3.

    Medical History and Concurrent Diseases
    6) Active bacterial infections, HIV/AIDS or other severe disease that would preclude study participation.
    7) Gastrointestinal tract disease or prior surgery, resulting in an inability to take or absorb oral medication.
    8) Other primary malignancy except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer.
    9) Mental incapacitation or psychiatric illness that would preclude study participation
    10) Uncontrolled or significant cardiovascular disease including: myocardial infarction within 12 months, uncontrolled angina within 6 months, Class III-IV New York Heart Association (NYHA) congestive heart failure, grade 3 cardiac valve dysfunction

    Physical and Laboratory Test Findings
    11) Clinically significant ascites refractory to diuretic therapy
    12) Presence of portal-systemic encephalopathy
    13) Evidence of portal hypertension with bleeding esophageal or gastric varices within the past 2 months
    a) Prior variceal bleed permitted if patient has undergone banding and there has been no evidence of bleeding for 2 months
    14) Hyponatremia with sodium < 125 mEq/L

    Allergies and Adverse Drug Reactions
    15) History of allergy to BMS-582664 or related compounds.

    Prohibited Therapies and/or Medications
    16) Prior systemic therapy for HCC, including systemic chemotherapy, biological therapy, or hormone therapy.
    17) Patients with previous thalidomide or anti-angiogenesis therapy

    Other Exclusion Criteria
    18) Prisoners or patients who are compulsorily detained
    19) Subjects with a history of bleeding disorders and thrombosis, including portal vein thrombosis coagulopathy, and are on chronic anti-platelet therapy (aspirin > 300 mg/day, clopidrogel; patients entering trial on warfarin should have frequent monitoring of INR for at least the first month on study and may require longer monitoring to insure that degree of anticoagulation does not go outside the therapeutic range.)
    20) Subjects with fibrolamellar disease
    21) Subjects with portal-caval shunts
    22) Subjects who are on a liver transplant list
    23) Subjects who have any known history of known brain metastases. Should patient have any signs and symptoms of possible brain metastases, a CT/MRI of the brain should be conducted prior to enrollment as clinically indicated.
    24) Subjects with hepatitis B DNA levels ≥ 1,650 IU/ml using the Roche Taqman assay.
    25) Subjects with centrally located cavitating lung lesions.
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy Measures:
    The primary efficacy endpoint for this study is the 6 month progression free survival (PFS) rate.

    Secondary efficacy endpoints include: Tumor response rate, time to response, duration of response, progression free survival, disease control rate, patient reported symptoms, and survival.

    Response will be assessed according to the modified WHO criteria for tumor response. These assessments will be made every 6 weeks or more frequently if indicated. Serum levels of AFP will be monitored.
    Disease progression and tumor assessment will be confirmed by an Independent Response Review Committee (IRRC).

    Primary Safety Outcome Measures:
    Safety will be assessed on the treated population and based on medical review of adverse event reports and the results of vital sign measurements, electrocardiograms, echocardiograms, physical examinations, and clinical laboratory tests. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance. Laboratory values, adverse events and other symptoms will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

    Pharmacokinetics:
    BMS-582664 plasma concentration data will be used in conjunction with samples from other studies as part of the population PK assessment.

    Pharmacodynamic Measures:
    Pharmacodynamic markers will be measured in plasma samples collected at specified intervals.
    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 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 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 Yes
    E.8.1.7.1Other trial design description
    Cross-over possibility for subjects randomized to the doxo arm, for unequivocal disease progression
    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 concerned4
    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 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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months11
    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 40
    F.4.2.2In the whole clinical trial 130
    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)
    All randomized subjects will be followed for disease progression & survival.
    Patients who discontinued due to toxicity or any reason other than confirmed tumor progression will have tumor assessments every 6 weeks until confirmed progression.
    For survival, phone contact will be conducted every 6 weeks after administration of last dose of study drug until death.
    Subjects treated on the doxorubicin arm will be allowed to cross-over to the BMS-582664 arm for unequivocal disease progression
    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 Decision2007-02-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-01-19
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2010-04-16
    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-Mon May 06 12:04:47 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA