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    The EU Clinical Trials Register currently displays   36107   clinical trials with a EudraCT protocol, of which   5935   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2007-005017-19
    Sponsor's Protocol Code Number:BO20924
    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:2008-01-31
    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 number2007-005017-19
    A.3Full title of the trial
    Open-label, multi-center, randomized, two stage adaptive design study of the combination of bevacizumab with standard chemotherapy in minor patients with metastatic rhabdomyosarcoma, non-rhabdomyosarcoma soft-tissue sarcoma or Ewing’s sarcoma/soft-tissue primitive neuroectodermal tumors.
    A.4.1Sponsor's protocol code numberBO20924
    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 SponsorF. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    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 Yes
    D.2.1.1.1Trade name Avastin®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 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.3.8INN - Proposed INNBevacizumab
    D.3.9.1CAS number 216974-75-3
    D.3.9.2Current sponsor codeRO4876646
    D.3.9.3Other descriptive namerhuMAb, VEGT, anti-VEGF
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 typeRecombinant humanised monoclonal antibody
    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
    Metastatic rhabdomyosarcoma, metastatic non rhabdomyosarcoma soft-tissue sarcoma, metastatic Ewing's sarcoma/soft-tissue primitive neuroectodermal tumors (PNET) in childhood and adolescent patients.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10015562
    E.1.2Term Ewing's sarcoma metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10015761
    E.1.2Term Extra-osseous Ewing's sarcoma metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10015568
    E.1.2Term Ewing's tumor metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10058253
    E.1.2Term Ewing's tumour metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10035639
    E.1.2Term PNET of bone metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10042864
    E.1.2Term Synovial sarcoma metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10016635
    E.1.2Term Fibrosarcoma metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10029274
    E.1.2Term Neurofibrosarcoma metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10024629
    E.1.2Term Liposarcoma metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10060651
    E.1.2Term Malignant hemangiopericytoma metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10039026
    E.1.2Term Rhabdomyosarcoma previously untreated
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the feasibility and efficacy of the combination of bevacizumab with standard chemotherapy as compared with standard chemotherapy alone in childhood and adolescent patients with metastatic rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft-tissue sarcoma (NRSTS), or Ewing’s sarcoma (ES)/soft-tissue PNET, as assessed by:
    • Incidence rate of patients with dose discontinuation or dose modification/delay.
    • Event-free survival (EFS) (2nd stage only)
    E.2.2Secondary objectives of the trial
    To determine the safety, tolerability and efficacy of the combination of bevacizumab with standard chemotherapy as compared with standard chemotherapy alone in patients with metastatic rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft-tissue sarcoma (NRSTS) or Ewing’s sarcoma(ES)/soft-tissue PNET, as assessed by:
    • Adverse event profile.
    • Response rate (according to RECIST).
    • Overall survival.
    • Duration of response.

    To characterize:
    • The pharmacokinetic (PK) characteristics of bevacizumab when combined with standard chemotherapy in childhood and adolescent patients.
    • Serum biomarker and tumor marker changes.

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent of patient/parent/legally acceptable
    representative (latest approved version by the Independent Ethics Committee
    [IEC]/Institutional Review Board [IRB]), obtained prior to any study-specific
    procedures.
    2. Age prior to treatment start greater than or equal to 2 years and less than or
    equal to 17 years.
    3. Newly diagnosed, histologically documented, patients with one of the following
    diseases:
    • Metastatic rhabdomyosarcoma (RMS) - Risk factors (at least two of the RMS
    specific risk factors are required for the 1st stage of the study):
    - Patients greater than or equal to 10 years of age.
    - Bone or bone marrow involvement (considered as 1 site).
    - More than two different organs with metastatic disease.
    - Unfavorable primary sites: extremities (including buttocks and shoulder) and
    trunk.
    • Metastatic non-rhabdomyosarcoma soft-tissue sarcoma (NRSTS).
    • Metastatic Ewing’s sarcoma (ES)/soft-tissue primitive neuroectodermal tumor
    (PNET) - Risk factors (at least one of these ES/PNET specific risk factors is
    required for the 1st stage of the study):
    - Bone metastases.
    - Bone marrow metastases.
    4. Age-adapted performance status and life expectancy adequate for chemotherapy
    according to the protocol.
    5. Adequate bone marrow function:
    • Absolute neutrophil count (ANC) greater than or equal to 1.0 x 1'000'000'000/L
    and WBC greater than or equal to 2.0 x 1'000'000'000/L.
    • Platelet count greater than or equal to 100 x 1'000'000'000/L (in case of bone
    marrow involvement greater than or equal to 75 x1'000'000'000/L).
    • Hb > 7.5 g/dL (75g/L - including after transfusion).
    6. Adequate blood clotting: PT-INR less than or equal to 1.5 and aPTT less than or
    equal to 1.5 x upper limit of normal (ULN) within 7 days prior to treatment start.
    7. Adequate liver function:
    • Serum (total) bilirubin less than or equal to 1.5 x ULN.
    • AST and ALT less than or equal to 2.5 x ULN in patients without liver
    metastases, less than or equal to 5 x ULN in patients with liver metastases.
    8. Adequate renal function:
    • Serum creatinine < 1.5 x ULN for age; if serum creatinine is > 1.5 x ULN for age,
    the creatinine clearance (or radioisotope GFR) must be >70 mL/min/1.73 m2.
    • Urine dipstick < 2+ for proteinuria. Patients who have greater than or equal to
    2+ of proteinuria on dipstick urinalysis should undergo a 24-hour urine
    collection; children and adolescents less than or equal to 12 years must have
    less than or equal to 500 mg of protein/24 hours and patients > 12 years must
    have less than or equal to 1 g of protein/24 hours.
    • No clinical evidence of nephrotic syndrome.
    9. Adequate cardiac function (Shortening Fraction (SF) greater than or equal to 28%)
    at screening, as determined by echocardiography; no evident and clinically
    significant symptoms of CHF (must be < class II of classification for
    heart failure (New York Heart Association (NYHA) or Ross scale).
    E.4Principal exclusion criteria
    1. Previous malignant tumors.
    2. Prior systemic anti-tumor treatment.
    3. Evidence of symptomatic spinal cord compression, CNS or brain metastases;
    patients must undergo a MRI or CT scan of the brain and/or spine in case of
    suspected brain metastatic disease.
    4. Tumor invading major blood vessels (CT scan based evidence); the investigator or
    radiologist must exclude evidence of tumor that is fully contiguous with,
    surrounding, or extending into the lumen of a major blood vessel (e.g. pulmonary
    artery or superior vena cava).
    5. Major surgical procedures or anticipation of the need for major surgery (other
    than the standard per protocol surgery) between screening and the first safety
    follow-up visit is considered incompatible with the use of bevacizumab; minor
    surgical procedures, including biopsy similar to and including central venous
    access device placement, within less than 7 days prior to randomization, or
    anticipated treatment start before the wound has healed.
    6. Documentation of clinically evident non-healing wound (as determined by the
    investigator), peptic ulcer or bone fracture.
    7. Current or recent (within 30 days prior to study start) treatment with another
    investigational drug or participation in another investigational study.
    8. Increased risk of gastrointestinal, renal, bone marrow, or congenital bleeding
    disorders.
    9. History or evidence of severe uncontrolled intercurrent illness at study entry, e.g.
    • Uncontrolled seizures.
    • Any bleeding or clotting diathesis, e.g. venous or arterial thromboembolic events
    (VTE, ATE), pulmonary embolism (PE).
    Any clinically significant (i.e. active) cardiovascular disease, e.g. cerebrovascular
    accidents (CVAs)/stroke, myocardial infarction (MI), transient ischemic attack
    (TIAs), unstable angina, or severe cardiac arrhythmia; clinical evidence of
    arterial hypertension, specified as systolic and diastolic BP greater than or equal
    to 95th percentile for age, gender and height (see Appendix 7).
    • Any other disease, metabolic or psychological dysfunction, physical examination
    finding, or clinical laboratory finding giving reasonable suspicion of a disease or
    condition that contraindicates use of an investigational drug, or places the
    patient at unacceptable risk from treatment complications.
    • General or peripheral neuropathy greater than or equal to grade 2 which is not
    induced by the underlying malignant disease.
    • Uncontrolled infection.
    10. Known hypersensitivity to:
    • Any component of study drugs or ingredients.
    • Chinese hamster ovary products or other recombinant human or humanized
    antibodies.
    11. Ongoing (for greater than or equal to 10 days prior to the 1st dose of study
    treatment) antithrombotic treatment, i.e. with aspirin or other platelet inhibitors,
    anticoagulants including thrombolytic agents, unfractionated or low-molecular
    weight heparins, or coumarin-derived anticoagulants; well-controlled
    anticoagulation is permitted as primary prophylaxis against thromboembolic
    events (TEs) and/or for maintenance of patency of a central access venous
    device (CVAD).
    12. Pregnancy and/or lactation: a negative serum pregnancy test in all female
    patients aged greater than or equal to 12 years (to be confirmed by
    urine test if serum test was performed more than 7 days prior to treatment
    start) must be obtained before treatment start; fertile patients with potential to
    bear or father a child must use an effective method of contraception.
    13. Patients not able to comply with the protocol.
    14. Patients not able to comply with the long-term follow-up at the investigational
    site.

    E.5 End points
    E.5.1Primary end point(s)
    Stage 1
    The primary endpoint of the first stage of the study is the incidence rate of patients with dose discontinuation or dose modification/delay of any component of study treatment.
    Stage 2
    The primary endpoint of the second stage of the study is an exploratory analysis of the event-free survival defined as time between randomization and insufficient therapeutic response or death due to any cause. Patients without an event will be censored at the last follow up for progression. Patients with no post baseline follow up for progression will be censored at the day of randomization.
    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 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 Yes
    E.6.13.1Other scope of the trial description
    Biomarkers analysis
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase I/II two stage adaptive design
    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
    Adaptive: after formal safety analysis of I stage, recruitment into II stage to max 150 pts
    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
    bevacizumab+Standard chemotherapy vs Standard chemotherapy
    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 EEA45
    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 final (end of stage II) analysis will be performed approximately 19 months after the last patient has been randomized.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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) Yes
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state45
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 150
    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 Decision2008-02-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-03-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-04-25
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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