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   44335   clinical trials with a EudraCT protocol, of which   7366   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:
    AN OPEN LABEL RANDOMISED PHASE II STUDY COMPARING AZD2014 VERSUS EVEROLIMUS IN PATIENTS WITH ADVANCED METASTATIC RENAL CANCER AND PROGRESSION ON VEGF TARGETED THERAPY

    Summary
    EudraCT number
    		 2012-002874-30
    Trial protocol
    		 GB  
    Global end of trial date
    31 Jan 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Jul 2016
    First version publication date
    06 Jul 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    008424QM
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01793636
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Queen Mary University London
    Sponsor organisation address
    2-4 Walden Street, , London, United Kingdom, E12EF
    Public contact
    Marianne Tomsa, Centre for Experimental Cancer Medicine, Queen Mary University London, bci-zebra@qmul.ac.uk
    Scientific contact
    Thomas Powles, Centre for Experimental Cancer Medicine, Queen Mary University London, bci-zebra@qmul.ac.uk
    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
    31 Jan 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jan 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective is to investigate if AZD2014 is associated with an improvement in progression free survival (PFS) compared to everolimus.
    Protection of trial subjects
    Side effects were closely monitored during and after the study. Patients were required to attend clinic weekly for the first four weeks and then every 4 weeks whilst they were on study medication where adverse events were recorded. The patient information sheet included details on expected adverse events for patients to look out for and also detailed that unexpected events may occur. The independent data monitoring committee for the trial was in place throughout to closely assess the side effects of the drugs on a regular basis and the trial results to make sure there were no excess risks to patients. On-site monitoring was performed throughout the study to provide real time review of source data to allow for early detection signals. There were potential risks due to radiation, from additional scans that were carried out as part of this study. A medical physics expert and clinical radiology expert reviewed the associated risks and confirmed that they were within reasonable limits for this patient group.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Feb 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 49
    Worldwide total number of subjects
    49
    EEA total number of subjects
    49
    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)
    31
    From 65 to 84 years
    18
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Starting in February 2013, patients were randomised (1:1) to AZD2014 or everolimus at 10 centres across the UK. Trial was stopped early in June 2014.

    Pre-assignment
    Screening details
    		 Inclusion criteria included patients with advanced or metastatic ccRCC and progression of disease after exposure to at least 1 VEGF-targeted therapy. 67 patients were assessed for eligibility, however only 49 were randomised. 18 patients were excluded prior to randomised as their screening assessments showed they did not meet inclusion criteria.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    NA

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 AZD2014 (50mg twice daily)
    Arm description
    		 AZD2014 (50mg twice daily)
    Arm type
    		 Experimental

    Investigational medicinal product name
    AZD2014
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50mg twice a day until disease progression.

    Arm title
    		 Everolimus (10mg once daily)
    Arm description
    		 Everolimus (10mg once daily)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Everolimus
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10mg once a day until disease progression.

    Number of subjects in period 1
    		AZD2014 (50mg twice daily) Everolimus (10mg once daily)
    Started
    26
    23
    Completed
    26
    23

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    AZD2014 (50mg twice daily)
    Reporting group description
    		 AZD2014 (50mg twice daily)

    Reporting group title
    Everolimus (10mg once daily)
    Reporting group description
    		 Everolimus (10mg once daily)

    Reporting group values
    		 AZD2014 (50mg twice daily) Everolimus (10mg once daily) Total
    Number of subjects
    		 26 23 49
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 17 14 31
        From 65-84 years
    		 9 9 18
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 58 (48 to 67) 63 (52 to 67) -
    Gender categorical
    Units: Subjects
        Female
    		 4 4 8
        Male
    		 22 19 41
    MSKCC Risk Score
    Units: Subjects
        Good
    		 10 10 20
        Intermediate
    		 7 10 17
        Poor
    		 9 3 12
    Duration of first-line therapy
    Units: Subjects
        ≤6 months
    		 6 6 12
        ≥6 months
    		 20 17 37
    Number of prior therapies
    Units: Subjects
        = 1
    		 10 14 24
        > 1
    		 16 9 25
    Nephrectomy
    Units: Subjects
        Yes
    		 21 18 39
        No
    		 5 5 10
    Bone/liver/brain metastasis
    Units: Subjects
        Yes
    		 5 8 13
        No
    		 21 14 35
        Missing
    		 0 1 1
    ECOG Performance Status
    Units: Subjects
        1-2
    		 14 14 28
        Zero
    		 10 8 18
        Missing
    		 2 1 3

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    AZD2014 (50mg twice daily)
    Reporting group description
    		 AZD2014 (50mg twice daily)

    Reporting group title
    Everolimus (10mg once daily)
    Reporting group description
    		 Everolimus (10mg once daily)

    Primary: Progression-free survival

    		 Close Top of page
    End point title
    		 Progression-free survival
    End point description
    End point type
    Primary
    End point timeframe
    From randomisation until time of progression
    End point values
    		 AZD2014 (50mg twice daily) Everolimus (10mg once daily)
    Number of subjects analysed
    26
    23
    Units: months
        median (confidence interval 95%)
    1.8 (1.54 to 1.94)
    4.6 (2.92 to 5.82)
    Attachments
    		 Kaplan-Meier Curve - PFS at Interim Analysi
    Statistical analysis title
    		 Progression-free survival
    Comparison groups
    Everolimus (10mg once daily) v AZD2014 (50mg twice daily)
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.01
    Method
    		 Stratified Log-rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 6.5

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From informed consent to 30 days post last IMP
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4
    Reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Serious adverse events
    		 Overall trial
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 49 (40.82%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 49 (10.20%)
         occurrences causally related to treatment / all
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    Increased Blood Creatinine
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypertriglyceridaemia
         subjects affected / exposed
    4 / 49 (8.16%)
         occurrences causally related to treatment / all
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Lethargy
         subjects affected / exposed
    2 / 49 (4.08%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Decreased appetite
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    3 / 49 (6.12%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    3 / 49 (6.12%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Overall trial
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    48 / 49 (97.96%)
    Blood and lymphatic system disorders
    Increased LFTs
         subjects affected / exposed
    7 / 49 (14.29%)
         occurrences all number
    19
    Anaemia
         subjects affected / exposed
    21 / 49 (42.86%)
         occurrences all number
    35
    Increased blood cholesterol
         subjects affected / exposed
    10 / 49 (20.41%)
         occurrences all number
    32
    Increased blood creatinine
         subjects affected / exposed
    13 / 49 (26.53%)
         occurrences all number
    34
    Hypercalcaemia
         subjects affected / exposed
    4 / 49 (8.16%)
         occurrences all number
    5
    Hyperglycaemia
         subjects affected / exposed
    11 / 49 (22.45%)
         occurrences all number
    26
    Hypertriglyceridaemia
         subjects affected / exposed
    10 / 49 (20.41%)
         occurrences all number
    28
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    16 / 49 (32.65%)
         occurrences all number
    21
    Lethargy
         subjects affected / exposed
    12 / 49 (24.49%)
         occurrences all number
    19
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    11 / 49 (22.45%)
         occurrences all number
    12
    Decreased appetite
         subjects affected / exposed
    9 / 49 (18.37%)
         occurrences all number
    9
    Diarrhoea
         subjects affected / exposed
    8 / 49 (16.33%)
         occurrences all number
    10
    Nausea
         subjects affected / exposed
    11 / 49 (22.45%)
         occurrences all number
    15
    Vomiting
         subjects affected / exposed
    6 / 49 (12.24%)
         occurrences all number
    6
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    11 / 49 (22.45%)
         occurrences all number
    15
    Dyspnoea
         subjects affected / exposed
    9 / 49 (18.37%)
         occurrences all number
    9
    Infections and infestations
    Infection
         subjects affected / exposed
    7 / 49 (14.29%)
         occurrences all number
    10

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Feb 2013
    Change of Principal Investigators and addition of participating sites
    14 Oct 2013
    Expansion of details regarding risks of CT scans added to PIS/ICF
    13 Feb 2014
    Changes to Principal Investigators and addition of new sites only
    31 Mar 2014
    Administrative updates only.
    23 Jun 2014
    Notification of recruitment suspension following DMC review
    10 Jul 2014
    Notification of early recruitment termination (patients to remain on follow-up)
    17 Dec 2014
    Reduction of follow-up period

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    10 Jun 2014
    The Data Monitoring Committee (DMC) met on the 9th June 2014 and confirmed that there is a statistically significant difference between the two treatment arms showing that the study drug AZD2014 is inferior. The DMC recommended that patients should be returned to standard care as soon as possible, and stated that it would be unethical to continue the study.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Small numbers precluded meaningful subset analysis, such as the importance of performance status or previous therapies with regard to outcome.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/26364551
    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-Fri May 09 22:40:53 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA