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   43865   clinical trials with a EudraCT protocol, of which   7286   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:2005-001376-12
    Sponsor's Protocol Code Number:BISMARK 2005
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-06-30
    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 ConcernedUK - MHRA
    A.2EudraCT number2005-001376-12
    A.3Full title of the trial
    Cost-effective use of BISphonphonates in metastatic bone disease - a comparison of bone MARKer directed zoledronic acid therapy to a standard schedule.
    A.3.2Name or abbreviated title of the trial where available
    BISMARK
    A.4.1Sponsor's protocol code numberBISMARK 2005
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberTo follow
    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 SponsorUniversity of Sheffield
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    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 Information not present in EudraCT
    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 nameZometa
    D.3.2Product code Zometa
    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.3.11 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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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
    Advanced breast cancer with bone metastases
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The purpose of the study is to investigate whether patients with breast cancer that has spread to the bones need a zoledronic acid treatment every 3-4 weeks as per the "standard" clinical schedule (i.e. how often it is given) or whether the schedule of zoledronic acid could be tailored to the individual patient by measuring the level of bone breakdown through a urine test.
    The primary objective of the study will be to compare the frequency (number) and timing of all skeletal related events (SREs) between the two schedules. Skeletal related events (SREs) are defined as bone complications such as fractures, additional treatment to the bone (e.g. radiotherapy or surgery), spinal cord compression and hypercalcaemia of malignancy.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are to compare the impact of both treatment regimens on:
    - Patient quality of life
    - The clinical burden of skeletal complications
    - Pain, performance status and analgesic use
    - The incidence of new bone metastases
    - Overall survival
    - Bisphosphonate use and expenditure on administration

    There are also three sub-studies that will compare the impact of both treatment regimens on the following in a sub-set of the trial patients:
    - Health care utilisation
    - Evaluation of the clinical use of a local "point of care" test as a means of calculating bone marker levels
    - Changes in serum markers of bone metabolism
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    •Patients with advanced breast cancer (primary breast cancer having been histologically confirmed) with radiographic confirmation of bone metastases (at least one bone scan lesion must be confirmed as metastatic on plain radiographs or CT/MR imaging)
    •Patients who have received a minimum of 4 months of zoledronic acid to treat metastatic bone disease prior to first study treatment (i.e. a minimum of 4 or 5 zoledronic acid treatments prior to first study treatment for patients receiving 4- or 3-weekly infusions, respectively)
    •Men or women aged ≥ 18 years
    •WHO (ECOG) performance status 0-2
    •Women of child-bearing potential / men must be using a reliable and appropriate method of contraception.
    •Ability to read and complete the QoL questionnaires
    •Urine sample taken for central laboratory Ntx analysis prior to first study treatment
    •Written informed consent.
    E.4Principal exclusion criteria
    •Bisphosphonate treatment within the 3 weeks prior to planned first study treatment
    •More than 12 months bisphosphonate (any) treatment for metastatic bone disease prior to first study treatment
    •Less than 4 months zoledronic acid treatment specifically for metastatic bone disease prior to first study treatment
    •Abnormal renal function as evidenced by a calculated creatinine clearance < 30 ml/minute (sample should be taken within the 28 days prior to randomisation)
    •Poor venous access (use of Hickman or PICC lines for treatment administration should be in accordance with local hospital policy)
    •Metabolic bone disease (e.g. Paget’s disease of bone. Presence of osteoporosis would not exclude a patient)
    •Inability to comply with study procedures, especially the reliable collection of urine samples for bone resorption marker measurements
    •Estimated life expectancy of < 6 months, as suggested by the presence of brain metastases or liver involvement with significantly impaired liver function (transaminases > 3 × upper limit of normal [ULN] or bilirubin > 1.5 × ULN - from blood taken within 28 days of randomisation)
    •Treatment with systemic bone seeking radioisotopes (e.g. strontium, samarium) within the 3 months prior to randomisation
    •Wide field (hemi-body) radiotherapy within the 3 months prior to randomisation
    - recent standard field, localised radiotherapy is not an exclusion criteria
    •Concomitant medication with drugs known to affect bone metabolism
    - calcitonin, high dose systemic corticosteroids (> 10 mg prednisolone/day or equivalent)
    •Pregnancy or breast-feeding
    •Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular), or a current or prior diagnosis of osteonecrosis of the jaw (ONJ)
    •Recent (within 4 weeks of randomisation) or planned dental or jaw surgery (e.g. extractions, implants)
    •History of prior cancers within the preceding 5 years (aside from ipsilateral / contralateral breast, non-melanomatous skin cancer, carcinoma in situ of the uterine cervix or superficial bladder cancer treated with curative intent)
    E.5 End points
    E.5.1Primary end point(s)
    To compare the frequency and timing of all skeletal related events (SREs). SREs are defined as:
    - Fractures: All clinical fractures will be reported and classified by site and shether considered to be disease related (i.e. pathological) or traumatic. In addition all fractures identified on follow-up radiographs (including vertebral wedge / compression fractures) will be recorded and classified by site and whether they are associated with pain (i.e. symptomatic)
    - Radiotherapy to bone either for relief of pain or to treat or prevent pathological fractures or spinal cord compression
    - Hypercalcaemia of malignancy (defined as corrected serum calcium of >2.7mmol/l)
    - Orthopaedic surgery to prevent or treat pathological fractures or to prevent or treat spinal cord compression
    - Spinal cord compression (defined as neurological dysfunction assocaited with imaging evidence of encroahment by tumour or bone onto the spinal cord / cauda equina)
    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 Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Optional sub-study to assess serum markers of bone metabolism
    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 No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    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
    Same IMP (zoledronic acid) but different schedule of administration
    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.8.5The 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 No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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
    For purposes of the MHRA application, end of the trial is defined as last patient last treatment visit. This is anticipated to be at approximately 5 years after the study commences recruitment. Following this, a non-interventional protocol will be undertaken to follow the secondary endpoint of "overall survival" at 3 and 5 years.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-06-30. Yes
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Patients with bone metastases. Women of child-bearing potential must be using reliable contraceptive
    F.4 Planned number of subjects to be included
    F.4.1In the member state1500
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1500
    F.4.2.2In the whole clinical trial 1500
    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)
    Following participation in the trial, patients will receive normal treatment for their cancer. This may include bisphosphonate use at the clinician's discretion. Patients may also receive any chemotherapy, biological or endocrine treatment considered appropriate by the treating physician during the course of the trial.
    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 Decision2005-08-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-07-27
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-08-04
    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-Sat Apr 27 19:53:06 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA