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    The EU Clinical Trials Register currently displays   43846   clinical trials with a EudraCT protocol, of which   7282   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:2004-002832-24
    Sponsor's Protocol Code Number:CZOL446GDE21
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-11-29
    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 ConcernedGermany - BfArM
    A.2EudraCT number2004-002832-24
    A.3Full title of the trial
    Influence of Zoledronic acid (Zometa®) on bone mineral density and bone ultrasonometry in premenopausal women with hormone receptor positive breast cancer and neoadjuvant or adjuvant chemoendocrine or endocrine treatment
    A.3.2Name or abbreviated title of the trial where available
    ProBONE II
    A.4.1Sponsor's protocol code numberCZOL446GDE21
    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 SponsorNovartis Pharma GmbH
    B.1.3.4CountryGermany
    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 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 4mg/5ml
    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 INNZoledronic acid
    D.3.9.2Current sponsor codeCGP42446
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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
    Hormonreceptor positive breast cancer in premenopausal women
    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
    This study is designed to demonstrate superiority of Zometa® (Zoledronic acid) 4 mg or adjusted dose based on renal function, given every 3 months over 24 months (infusion at month 0, 3, 6, 9, 12, 15, 18, and 21) in improving bone mineral density in premenopausal women with hormone receptor positive breast cancer and neoadjuvant or adjuvant chemoendocrine or endocrine treatment compared to placebo.
    E.2.2Secondary objectives of the trial
    Secondary objectives of the trial are to explore the influence of the therapy with Zometa® compared to placebo with regard to:
    •Bone mineral density (BMD) measured by DXA at dual hips and os calcis after 24 months
    •Bone mineral density (BMD) by QUS at os calcis and phalanges at 24 months
    •Course of biochemical markers of bone turn over (FSH, estradiol (E2), osteocalcin, PINP, procollagene-I-peptid, deoxypyridinoline in serum)
    •Pathologic Fractures (proportion of patients with at least one fracture, type of fracture(s), number of fractures per patient, time to first pathologic fracture) during 24 months
    •Development of metastases as assessed by X-ray, CT, bone scan or MRI (proportion of patients developing metastases, number and localization, metastases-free survival) during 24 months and during 60 months
    •Safety and tolerability (adverse events / serious adverse events; standard safety laboratory)
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    • Female patients with histologically confirmed incident invasive breast cancer (T1-4).
    • No evidence of distant metastasis (M0)
    • Patients under adjuvant chemoendocrine or endocrine therapy: Node negative (pN-) and Node positive (pN+; <= 4 positive lymph nodes) patients
    • Patients under neoadjuvant chemotherapy: no clinical evidence for nodal involvement
    • Hormone receptor status (ER and/or PgR) is positive (defined as >=10% receptor positive cells or >=10fmol receptor protein/mg cytosol protein or IRS >2)
    • Age >= 18 years
    • Patient is premenopausal: determined by spontaneous and regular menses at diagnosis of breast cancer or by premenopausal estradiol levels (>20ng/L) at diagnosis of breast cancer
    • Patient receives neoadjuvant chemotherapy or adjuvant standard chemoendocrine or endocrine therapy
    • Bone density at study entry > -2.5 T-Score
    • Patient has given written informed consent prior to any study-specific procedure
    • Patient should be available for Follow-up
    E.4Principal exclusion criteria
    •History of treatment or disease affecting bone metabolism (e.g., Paget’s disease, primary hyperparathyroidism)
    •Known visceral metastasis or bone metastases
    •Prior treatment with bisphosphonates
    •Previous or concomitant malignancy (not breast cancer) within the past 5 years except adequaetely treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease-free for five years
    •Severe physical or psychological concomitant diseases that might impair compliance with the provisions of the study protocol or that might impair the assessment of drug or patient safety, e.g. clinically significant ascites, cardiac failure, NYHA III or IV, clinically relevant pathologic findings in ECG
    •Other known concurrent, severe medical disorder jeopardizing the life of the patient in the immediate future (e.g., myocardial infarction in previous six months, angina pectoris despite treatment, uncontrolled severe arterial hypertension, progressive cardiac or respiratory failure)
    •Known hypersensitivity to bisphosphonates
    •Abnormal renal function as evidenced by a calculated creatinine clearance < 30 mL/minute. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula:
    CrCl= [140-age (years)] x weight (kg) {x 0.85 for female patients}
    [72 x serum creatinine (mg/dL)]
    •Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
    •Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)
    •Use of other investigational drugs (drugs not marketed for any indication) within 6 months before start of study and participation in other clinical study.
    •Pregnancy or lactation
    •Women of childbearing potential not applying a medically recognized form of contraception (i.e., oral contraceptives or implants, IUD, vaginal diaphragm or sponge, or condom with spermicide)
    •Known history or present abuse of alcohol or drugs (accepted social alcohol usage will not exclude the patient)
    •History of noncompliance to medical regimens and patients who are considered potentially unreliable or incapable of giving informed consent as judged by the investigator
    E.5 End points
    E.5.1Primary end point(s)
    Change in bone mineral density (BMD) measured by DXA at lumbar spine (L2-L4) between baseline and 24 months.
    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 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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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
    LPLV
    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 months10
    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 No
    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 2005-11-29. 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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state70
    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 Decision2005-07-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-07-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-05-19
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