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

    Download PDF

    Clinical Trial Results:
    A randomized, double-blind, placebo controlled, multicenter Phase II study to assess the efficacy and safety of Sorafenib added to standard treatment with Topotecan in patients with platinum-resistant recurrent ovarian cancer

    Summary
    EudraCT number
    		 2009-011922-33
    Trial protocol
    		 DE  
    Global end of trial date
    10 Feb 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Sep 2022
    First version publication date
    09 Sep 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    TRIAS2009
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01047891
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Charité – Universitätsmedizin Berlin
    Sponsor organisation address
    Charitéplatz 1, Berlin, Germany, 10117
    Public contact
    Dr Radoslav Chekerov, Department of Gynecology, Augustenburger Platz 1, 13353 Berlin, +49 030450 664399, radoslav.chekerov@charite.de
    Scientific contact
    Dr Radoslav Chekerov, Department of Gynecology, Augustenburger Platz 1, 13353 Berlin, +49 030450 664399, radoslav.chekerov@charite.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 May 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Feb 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Determination of the progression-free survival (PFS) of patients treated with topotecan + sorafenib versus topotecan + placebo
    Protection of trial subjects
    The study was conducted in accordance with the 1996 Declaration of Helsinki, the International Conference on Harmonisation Good Clinical Practice (GCP) recommendations, and provisions of the German Medicines Act and the GCP Ordinance of August 2000.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Jan 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 172
    Worldwide total number of subjects
    172
    EEA total number of subjects
    172
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    86
    From 65 to 84 years
    86
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Between 18 January 2010, and 19 September 2013, 185 patients were enrolled from 20 sites in Germany; Two patients in the sorafenib group had serious adverse events before treatment and were excluded from analyses

    Pre-assignment
    Screening details
    		 assessed for eligibility: 185 excluded: 11 randomised: 174

    Period 1
    Period 1 title
    Treatment
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sorafenib+topotecan Group
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sorafenib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400mg on days 6-15 every 21 days for six cycles followed by daily maintance sorafenib for up to 1 year in patients without progression

    Investigational medicinal product name
    Topotecan
    Investigational medicinal product code
    Other name
    Hycamtin
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.25 mg/m² on days 1-5

    Arm title
    		 Placebo+topotecan Group
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Topotecan
    Investigational medicinal product code
    Other name
    Hycamtin
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.25 mg/m² on days 1-5

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400mg placebo twice daily on days 6-15, repeated every 21 days for up to six cycles.

    Number of subjects in period 1
    		Sorafenib+topotecan Group Placebo+topotecan Group
    Started
    83
    89
    Completed
    47
    47
    Not completed
    36
    42
         Adverse event, serious fatal
    4
    -
         Consent withdrawn by subject
    11
    6
         N/A
    6
    3
         Adverse event, non-fatal
    6
    6
         Lost to follow-up
    1
    -
         disease progression
    8
    27
    Period 2
    Period 2 title
    Maintenance phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sorafenib+topotecan group
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sorafenib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400mg on days 6-15 every 21 days for six cycles followed by daily maintance sorafenib for up to 1 year in patients without progression

    Arm title
    		 Placebo+topotecan Group
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400mg placebo twice daily on days 6-15, repeated every 21 days for up to six cycles.

    Number of subjects in period 2
    		Sorafenib+topotecan group Placebo+topotecan Group
    Started
    47
    47
    Completed
    1
    0
    Not completed
    46
    47
         Adverse event, serious fatal
    -
    1
         Consent withdrawn by subject
    6
    -
         N/A
    2
    2
         Adverse event, non-fatal
    1
    2
         Lost to follow-up
    1
    -
         disease progression
    24
    29
         Protocol deviation
    12
    13

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Sorafenib+topotecan Group
    Reporting group description
    		 -

    Reporting group title
    Placebo+topotecan Group
    Reporting group description
    		 -

    Reporting group values
    		 Sorafenib+topotecan Group Placebo+topotecan Group Total
    Number of subjects
    		 83 89 172
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        median (full range (min-max))
    		 59 (31 to 78) 58 (25 to 79) -
    Gender categorical
    Units: Subjects
        No gender specifications
    		 83 89 172
    FIGO stage
    FIGO=International Federation of Gynecology and Obstetrics
    Units: Subjects
        Stage I
    		 0 4 4
        Stage II
    		 7 3 10
        Stage III
    		 49 54 103
        Stage IV
    		 18 20 38
        Unknown
    		 9 8 17
    Histology
    Units: Subjects
        Serous
    		 69 67 136
        Other
    		 14 22 36
    Grade
    Units: Subjects
        Grade 1
    		 3 2 5
        Grade 2
    		 22 25 47
        Grade 3
    		 49 58 107
        Unknown
    		 9 4 13
    Ascites
    Units: Subjects
        Yes
    		 30 33 63
        No
    		 48 54 102
        unknown
    		 5 2 7
    ECOG performance
    ECOG=Eastern Cooperative Oncology Group
    Units: Subjects
        Status 0
    		 45 47 92
        Status 1
    		 33 38 71
        Status 2
    		 3 1 4
        Unknown
    		 2 3 5
    Residual disease after primary debulking
    Units: Subjects
        No surgery
    		 11 12 23
        Microscopic
    		 25 26 51
        <1 cm
    		 16 17 33
        ≥1 cm
    		 13 15 28
        Missing/unknown
    		 18 19 37

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Sorafenib+topotecan Group
    Reporting group description
    		 -

    Reporting group title
    Placebo+topotecan Group
    Reporting group description
    		 -
    Reporting group title
    Sorafenib+topotecan group
    Reporting group description
    		 -

    Reporting group title
    Placebo+topotecan Group
    Reporting group description
    		 -

    Primary: Progression-free survival

    		 Close Top of page
    End point title
    		 Progression-free survival
    End point description
    The primary endpoint was investigator-assessed PFS, defined as the interval between first treatment cycle and disease progression or death from any cause.
    End point type
    Primary
    End point timeframe
    36 months
    End point values
    		 Sorafenib+topotecan Group Placebo+topotecan Group
    Number of subjects analysed
    83
    89
    Units: Months
        median (confidence interval 95%)
    6.7 (5.8 to 7.6)
    4.4 (3.7 to 5.0)
    Statistical analysis title
    		 Change of the PFS
    Comparison groups
    Sorafenib+topotecan Group v Placebo+topotecan Group
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 t-test, 2-sided
    Confidence interval

    Secondary: objective response rate by RECIST

    		 Close Top of page
    End point title
    		 objective response rate by RECIST
    End point description
    End point type
    Secondary
    End point timeframe
    60 months
    End point values
    		 Sorafenib+topotecan Group Placebo+topotecan Group
    Number of subjects analysed
    39
    50
    Units: percent
        number (not applicable)
    31
    12
    No statistical analyses for this end point

    Secondary: duration of response

    		 Close Top of page
    End point title
    		 duration of response
    End point description
    End point type
    Secondary
    End point timeframe
    60 months
    End point values
    		 Sorafenib+topotecan Group Placebo+topotecan Group
    Number of subjects analysed
    83
    89
    Units: Month
        median (confidence interval 95%)
    21.0 (17.3 to 24.7)
    14.0 (8.2 to 19.8)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    60 months
    Adverse event reporting additional description
    for more AE/SAE details see table 2 https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(18)30372-3 "open manuscript"
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    Topotecan/sorafenib
    Reporting group description
    		 Grad 3/4/5 were put together as sAE

    Reporting group title
    Topotecan/placebo
    Reporting group description
    		 -

    Serious adverse events
    		 Topotecan/sorafenib Topotecan/placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    80 / 83 (96.39%)
    82 / 89 (92.13%)
         number of deaths (all causes)
    2
    5
         number of deaths resulting from adverse events
    0
    Investigations
    Hypokalaemia
         subjects affected / exposed
    4 / 83 (4.82%)
    5 / 89 (5.62%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    4 / 83 (4.82%)
    4 / 89 (4.49%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ALT
         subjects affected / exposed
    2 / 83 (2.41%)
    4 / 89 (4.49%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leucopenia
         subjects affected / exposed
    58 / 83 (69.88%)
    47 / 89 (52.81%)
         occurrences causally related to treatment / all
    0 / 58
    0 / 47
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neutropenia
         subjects affected / exposed
    46 / 83 (55.42%)
    48 / 89 (53.93%)
         occurrences causally related to treatment / all
    0 / 46
    0 / 48
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    23 / 83 (27.71%)
    20 / 89 (22.47%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anamia
         subjects affected / exposed
    12 / 83 (14.46%)
    17 / 89 (19.10%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    10 / 83 (12.05%)
    4 / 89 (4.49%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    4 / 83 (4.82%)
    8 / 89 (8.99%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
    Additional description: Not associated with CTCAE term
         subjects affected / exposed
    1 / 83 (1.20%)
    4 / 89 (4.49%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Non-malignant ascites
         subjects affected / exposed
    4 / 83 (4.82%)
    6 / 89 (6.74%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    4 / 83 (4.82%)
    4 / 89 (4.49%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    5 / 83 (6.02%)
    5 / 89 (5.62%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    7 / 83 (8.43%)
    5 / 89 (5.62%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Hand-foot skin reaction
         subjects affected / exposed
    11 / 83 (13.25%)
    0 / 89 (0.00%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Other dermatological symptoms
         subjects affected / exposed
    11 / 83 (13.25%)
    0 / 89 (0.00%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Febrile neutropenia
         subjects affected / exposed
    6 / 83 (7.23%)
    5 / 89 (5.62%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Other infection
         subjects affected / exposed
    6 / 83 (7.23%)
    9 / 89 (10.11%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Topotecan/sorafenib Topotecan/placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    54 / 83 (65.06%)
    62 / 89 (69.66%)
    Investigations
    ALT
         subjects affected / exposed
    18 / 83 (21.69%)
    15 / 89 (16.85%)
         occurrences all number
    18
    15
    AST
         subjects affected / exposed
    21 / 83 (25.30%)
    15 / 89 (16.85%)
         occurrences all number
    21
    15
    Creatine
         subjects affected / exposed
    7 / 83 (8.43%)
    10 / 89 (11.24%)
         occurrences all number
    7
    10
    GGT
         subjects affected / exposed
    3 / 83 (3.61%)
    7 / 89 (7.87%)
         occurrences all number
    3
    7
    Hypokalaemia
         subjects affected / exposed
    5 / 83 (6.02%)
    6 / 89 (6.74%)
         occurrences all number
    5
    6
    Hyponatraemia
         subjects affected / exposed
    7 / 83 (8.43%)
    3 / 89 (3.37%)
         occurrences all number
    7
    3
    Vascular disorders
    Haemorrhage/bleeding
         subjects affected / exposed
    6 / 83 (7.23%)
    5 / 89 (5.62%)
         occurrences all number
    6
    5
    Nervous system disorders
    Neuropathy
         subjects affected / exposed
    18 / 83 (21.69%)
    23 / 89 (25.84%)
         occurrences all number
    18
    23
    Blood and lymphatic system disorders
    Leucopenia
         subjects affected / exposed
    15 / 83 (18.07%)
    23 / 89 (25.84%)
         occurrences all number
    15
    23
    Neutropenia
         subjects affected / exposed
    6 / 83 (7.23%)
    8 / 89 (8.99%)
         occurrences all number
    6
    8
    Thrombocytopenia
         subjects affected / exposed
    39 / 83 (46.99%)
    27 / 89 (30.34%)
         occurrences all number
    39
    27
    Anaemia
         subjects affected / exposed
    54 / 83 (65.06%)
    62 / 89 (69.66%)
         occurrences all number
    54
    62
    Lymphopenia
         subjects affected / exposed
    8 / 83 (9.64%)
    2 / 89 (2.25%)
         occurrences all number
    8
    2
    Oedema
         subjects affected / exposed
    6 / 83 (7.23%)
    14 / 89 (15.73%)
         occurrences all number
    6
    14
    General disorders and administration site conditions
    Coagulation
         subjects affected / exposed
    6 / 83 (7.23%)
    5 / 89 (5.62%)
         occurrences all number
    6
    5
    Fatigue
         subjects affected / exposed
    33 / 83 (39.76%)
    50 / 89 (56.18%)
         occurrences all number
    33
    50
    Weight loss
         subjects affected / exposed
    9 / 83 (10.84%)
    2 / 89 (2.25%)
         occurrences all number
    9
    2
    Diarrhoea
         subjects affected / exposed
    29 / 83 (34.94%)
    22 / 89 (24.72%)
         occurrences all number
    29
    22
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    29 / 83 (34.94%)
    25 / 89 (28.09%)
         occurrences all number
    29
    25
    Nausea
         subjects affected / exposed
    48 / 83 (57.83%)
    41 / 89 (46.07%)
         occurrences all number
    48
    41
    Vomiting
         subjects affected / exposed
    31 / 83 (37.35%)
    31 / 89 (34.83%)
         occurrences all number
    31
    31
    Abdominal pain
         subjects affected / exposed
    25 / 83 (30.12%)
    26 / 89 (29.21%)
         occurrences all number
    25
    26
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    15 / 83 (18.07%)
    12 / 89 (13.48%)
         occurrences all number
    15
    12
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    46 / 83 (55.42%)
    47 / 89 (52.81%)
         occurrences all number
    46
    47
    Hand-foot skin reaction
         subjects affected / exposed
    25 / 83 (30.12%)
    3 / 89 (3.37%)
         occurrences all number
    25
    3
    Other dermatological symptoms
         subjects affected / exposed
    39 / 83 (46.99%)
    20 / 89 (22.47%)
         occurrences all number
    39
    20
    Renal and urinary disorders
    Renal/genitourinary
         subjects affected / exposed
    4 / 83 (4.82%)
    10 / 89 (11.24%)
         occurrences all number
    4
    10
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    4 / 83 (4.82%)
    2 / 89 (2.25%)
         occurrences all number
    4
    2
    Other infection
         subjects affected / exposed
    15 / 83 (18.07%)
    12 / 89 (13.48%)
         occurrences all number
    15
    12

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jun 2010
    expanded to two prior therapies for relapsed disease in Protocol
    04 May 2011
    eligibility of patients treated with bevacizumab or vascular endothelial growth factor receptor tyrosine kinase inhibitors and increasement of the recruitment period

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    -maintenance treatment only 12 months -completion of the QoL not mandatory

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/30100379
    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 May 04 08:54:26 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA