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   43851   clinical trials with a EudraCT protocol, of which   7283   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:2011-005335-97
    Sponsor's Protocol Code Number:GO25632
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2012-10-19
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2011-005335-97
    A.3Full title of the trial
    A phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of bevacizumab, and associated biomarkers, in combination with paclitaxel compared with paclitaxel plus placebo as first-line treatment of patients with HER2-negative metastatic breast cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the efficacy and safety of bevacizumab in combination with chemotherapy in patients with breast cancer that spread to other tissues.
    A.3.2Name or abbreviated title of the trial where available
    Meridian
    A.4.1Sponsor's protocol code numberGO25632
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01663727
    A.7Trial is part of a Paediatric Investigation Plan No
    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 supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF.Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.com
    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 Ltd.
    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.3.1Product nameBevacizumab
    D.3.2Product code RO4876646/F02
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    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 VEGF, anti-VEGF
    D.3.9.4EV Substance CodeSUB16402MIG
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboConcentrate for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HER2-negative metastatic breast cancer.
    E.1.1.1Medical condition in easily understood language
    Breast cancer that spread to other tissues
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10027475
    E.1.2Term Metastatic breast cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of bevacizumab + paclitaxel compared with placebo + paclitaxel as first-line treatment in patients with HER2-negative metastatic breast cancer as measured by:
    - PFS based on investigator tumor assessment in the intent-to treat (ITT) patient population
    - PFS based on investigator tumor assessment in ITT patients with high plasma VEGF-A levels
    E.2.2Secondary objectives of the trial
    1) To evaluate on the ITT population and the VEGF-A high subset the efficacy of bevacizumab + paclitaxel compared with placebo + paclitaxel as first-line treatment in patients with HER2-negative MBC as measured by:
    - OS
    - Objective response rate for patients with measurable disease at baseline, as assessed by investigator
    -Duration of objective response for patients with measurable disease at baseline
    - One-year survival
    2) In addition, an interaction of treatment effect with the VEGF-A level for PFS will be performed in the ITT population
    3) To evaluate the safety of bevacizumab + paclitaxel compared with placebo + paclitaxel as first-line treatment in patients with HER2-negative MBC, focusing on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) , Version 4 .0, all-grade treatment-emergent adverse events.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically or cytologically confirmed, HER2 negative adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
    2. Signed Informed Consent Form
    3. Age ≥ 18 years
    4. ECOG performance status of 0 or 1
    5. Ability and capacity to comply with study and follow up procedures
    6. For men and women with reproductive potential (women < 2 years
    after last menstruation and not surgically sterile), use of an acceptable and
    effective method of non-hormonal contraception (intrauterine contraceptive device or barrier method of contraception in conjunction with spermicidal jelly) during treatment and for at least 6 months after the completion of treatment; use of oral hormonal contraceptives is allowed, however, concurrent use of at least one non-hormonal contraceptive method is mandatory.
    7. For patients who have received recent radiotherapy, recovery prior to randomization from any significant (Grade ≥ 3) acute toxicity, and radiation treatments have to be completed more than 3 weeks from randomization
    E.4Principal exclusion criteria
    Disease-Specific Exclusions
    1. HER2-positive status.
    2. Prior chemotherapy for locally recurrent or metastatic disease
    3. Prior hormonal therapy < 2 weeks prior to randomization.
    4. Prior adjuvant or neo-adjuvant chemotherapy is allowed, provided its conclusion has been for at least 12 months prior to randomization.
    5. Investigational therapy within 28 days of randomization
    General Medical Exclusions
    6. Life expectancy of < 12 weeks
    7. Inadequate organ function
    8. Persistent Grade ≥ 3 sensory neuropathy
    9. Uncontrolled serious medical or psychiatric illness
    10. Active infection requiring intravenous (IV) antibiotics at screening
    11. Pregnancy (positive pregnancy test) or lactation.
    12. Patients with a history of bilateral breast cancer.
    13. History of other malignancies within 5 years prior to screening, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
    Bevacizumab-Specific Exclusions
    14. Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
    15. Prior history of hypertensive crisis or hypertensive encephalopathy
    16. New York Heart Association Class II or greater, CHF/left ventricular ejection fraction < 55%
    17. History of myocardial infarction or unstable angina within 6 months prior to randomization
    18. History of stroke or transient ischemic attack within 6 months prior to randomization
    19. Known CNS disease except for treated brain metastasis.
    20. Significant vascular disease
    21. History of hemoptysis
    22. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
    23. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for major surgical procedure during the course of the study
    24. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to randomization
    25. History of abdominal fistula or gastrointestinal (GI) perforation within 6 months prior to randomization
    26. Serious, non-healing wound, active ulcer, or untreated bone fracture
    27. Proteinuria at screening
    28. Known hypersensitivity to any component of bevacizumab
    29. Prior therapy with bevacizumab, sorafenib, sunitinib, or other
    VEGF pathway–targeted therapy
    Paclitaxel-Specific Exclusions
    30. History of severe hypersensitivity to paclitaxel or to any of the excipients, especially macrogolglycerol ricinoleate
    31. Paclitaxel should not be administered to patients with baseline neutrophil count <1500/mm3.
    E.5 End points
    E.5.1Primary end point(s)
    Coprimary endpoints:
    1) PFS in the intention-to-treat population (all randomized patients)
    2) PFS in the patients with high VEGF-A levels
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary analysis of PFS will occur when both (I) 326 PFS events in all patients and (II) 146 PFS events in the VEGF-A high subgroup have been observed.
    E.5.2Secondary end point(s)
    1) Objective Response Rate
    2) Duration of Objective Response
    3) 1-year Survival Rate
    4) Overall Survival
    5) Treatment/VEGF-A Interaction Test for PFS
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) Objective response, 2)duration of response, first IA of OS, AEs will be analyzed at the same time with final PFS.
    3) Primary 1-year survival rate will be analyzed when OS crosses the boundary or at the time of final OS event maturity.
    4) Final OS will also be conducted when both (I) approximately 309 deaths in all patients and (II) approximately 170 deaths in the VEGF-A high subgroup have been observed.
    5)At the timepoint of the primary (final) analysis of PFS
    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 No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarker assessment
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    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) 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 No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Pts under PTX+BEV at time of unblinding after additional OS IA can continue BEV treatment OL
    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 + paclitaxel vs. bevacizumab placebo + paclitaxel
    E.8.2.4Number of treatment arms in the trial2
    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 EEA59
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Belgium
    Brazil
    Bulgaria
    Chile
    Germany
    Italy
    Japan
    Korea, Republic of
    Panama
    Romania
    Russian Federation
    South Africa
    Ukraine
    United Kingdom
    United States
    Vietnam
    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 end of the study is defined as the date when 394 deaths in the ITT population have been observed. This follow-up OS analysis is expected approximately 6.5 years after the first patient is 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 months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months6
    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 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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 384
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 96
    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 state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 93
    F.4.2.2In the whole clinical trial 480
    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)
    Patients who are still receiving study medication (bevacizumab) at the time of study closure will end their study participation in this protocol and may continue their treatment according to standard of care, as defined by the treating physician.
    In case the physician decides to continue treatment with bevacizumab at the time of the study closure, costs for commercial medication may be refunded by the Sponsor until disease progression if permitted by local laws and regulations.
    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 Decision2012-09-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-10-18
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2017-11-21
    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 20 09:12:45 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA