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   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).

    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:
    Phase I ’run in’ study followed by randomised phase II trial testing intra-tumoural hydrogen peroxide as a radiation sensitizer in patients with locally advanced/recurrent breast cancer in terms of toxicity and tumour response

    Summary
    EudraCT number
    		 2016-000833-40
    Trial protocol
    		 GB  
    Global end of trial date
    12 Nov 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Jun 2021
    First version publication date
    02 Jun 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CCR4502
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02757651
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 ClinicaTrials.gov: NCT02757651
    Sponsors
    Sponsor organisation name
    The Institute of Cancer Research
    Sponsor organisation address
    123 Old Brompton Road, London, United Kingdom, SW7 3RP
    Public contact
    Research Coordinator, The Institute of Cancer Research, 0044 020 8661 3460, lone.gothard@icr.ac.uk
    Scientific contact
    Research Coordinator, The Institute of Cancer Research, 0044 020 8661 3460, lone.gothard@icr.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
    15 Jan 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Nov 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Nov 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Phase I Objective: To confirm safety reported in Japanese studies. Endpoint: Patient reported maximum intra-tumoural pain intensity over duration of treatment. Phase II is currently underway under protocol CCR5119 / EudraCT 2019-001709-25
    Protection of trial subjects
    Subjects were monitored closely for pain and skin toxicity and medication and advice provided as required.
    Background therapy
    		 N/a
    Evidence for comparator
    		 N/a
    Actual start date of recruitment
    01 Oct 2016
    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: 12
    Worldwide total number of subjects
    12
    EEA total number of subjects
    0
    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)
    4
    From 65 to 84 years
    6
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects were recruited between 8-Feb-2017 and 13-Jun-2018. 13 subjects were consented, but 1/13 withdrew due to clinical deterioration prior to any treatment and was not included in the analysis.

    Pre-assignment
    Screening details
    		 Screening data was not collected for patients approached but not entered into the trial.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    N/a

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Daily radiotherapy
    Arm description
    		 49.5 Gy in 18 daily fractions of radiotherapy + twice weekly H2O2 injections starting week 2
    Arm type
    		 Experimental

    Investigational medicinal product name
    H2O2
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intratumoral use
    Dosage and administration details
    A slow-release 0.5% H2O2 solution created by mixing 0.4ml of 3% H2O2 with 2.0ml OSTENIL (sodium hyaluronate)

    Arm title
    		 Twice weekly radiotherapy
    Arm description
    		 36 Gy in 6 fractions of radiotherapy + twice weekly H2O2 injections starting week 2
    Arm type
    		 Experimental

    Investigational medicinal product name
    H2O2
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intratumoral use
    Dosage and administration details
    A slow-release 0.5% H2O2 solution created by mixing 0.4ml of 3% H2O2 with 2.0ml OSTENIL (sodium hyaluronate)

    Number of subjects in period 1
    		Daily radiotherapy Twice weekly radiotherapy
    Started
    6
    6
    Completed
    6
    6

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 12 12
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 4 4
        From 65-84 years
    		 6 6
        85 years and over
    		 2 2
    Gender categorical
    Units: Subjects
        Female
    		 10 10
        Male
    		 2 2
    Subject analysis sets

    Subject analysis set title
    All subjects
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All 12 subjects analysed as part of this phase 1 safety study

    Subject analysis sets values
    		 All subjects
    Number of subjects
    12
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    4
        From 65-84 years
    6
        85 years and over
    2
    Age continuous
    Units:
        
    ( )
    Gender categorical
    Units: Subjects
        Female
    10
        Male
    2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Daily radiotherapy
    Reporting group description
    		 49.5 Gy in 18 daily fractions of radiotherapy + twice weekly H2O2 injections starting week 2

    Reporting group title
    Twice weekly radiotherapy
    Reporting group description
    		 36 Gy in 6 fractions of radiotherapy + twice weekly H2O2 injections starting week 2

    Subject analysis set title
    All subjects
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All 12 subjects analysed as part of this phase 1 safety study

    Primary: Patient reported maximum intra-tumoural pain intensity over duration of treatment

    		 Close Top of page
    End point title
    		 Patient reported maximum intra-tumoural pain intensity over duration of treatment
    End point description
    The maximum intra-tumoural pain intensity taken from the pain questionnaire provided to patients before and 0-24 hours after each KORTUC injection. The maximum intensity for all patients were then presented as proportions and frequencies
    End point type
    Primary
    End point timeframe
    Duration of treatment
    End point values
    		 Daily radiotherapy Twice weekly radiotherapy All subjects
    Number of subjects analysed
    6
    6
    12
    Units: Pain intensity
        number (not applicable)
    6
    6
    12
    Statistical analysis title
    		 Summary of pain intensity
    Statistical analysis description
    Description of patient reported maximum intra-tumoural pain intensity over duration of treatment
    Comparison groups
    Daily radiotherapy v Twice weekly radiotherapy v All subjects
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    Method
    		 Descriptive analysis
    Parameter type
    		 Median and IQR
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 4
    Notes
    [1] - Descriptive analysis

    Secondary: Skin toxicity

    		 Close Top of page
    End point title
    		 Skin toxicity
    End point description
    Proportion of patients with grade ≥3 acute skin toxicity at any time from start of radiotherapy to 4 weeks after completion
    End point type
    Secondary
    End point timeframe
    From start of radiotherapy to 4 weeks post radiotherapy
    End point values
    		 Daily radiotherapy Twice weekly radiotherapy All subjects
    Number of subjects analysed
    6
    6
    12
    Units: Grade 3 or more Toxicity
        Tox Grade < 3
    5
    6
    11
        Tox Grade >=3
    1
    0
    1
    Statistical analysis title
    		 Proportion of patients with grade≥3 acute skin tox
    Statistical analysis description
    Proportion of patients with grade ≥3 acute skin toxicity at any time from start of radiotherapy to 4 weeks after completion
    Comparison groups
    Daily radiotherapy v Twice weekly radiotherapy v All subjects
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    Method
    		 Descriptive analysis
    Parameter type
    		 Proportion
    Point estimate
    8.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 38.5
    Notes
    [2] - Descriptive analysis

    Secondary: Tumour response

    		 Close Top of page
    End point title
    		 Tumour response
    End point description
    Tumour response 3, 6, 9 and 12 months post- radiotherapy according to RECIST 1.1 criteria
    End point type
    Secondary
    End point timeframe
    3 - 12 months post radiotherapy
    End point values
    		 Daily radiotherapy Twice weekly radiotherapy All subjects
    Number of subjects analysed
    6
    6
    12
    Units: Best response
        CR
    1
    0
    1
        PR
    4
    6
    10
        SD
    0
    0
    0
        PD
    1
    0
    1
    Statistical analysis title
    		 Best response
    Statistical analysis description
    Best tumour response 3, 6, 9 and 12 months post-radiotherapy according to RECIST 1.1 criteria
    Comparison groups
    Daily radiotherapy v Twice weekly radiotherapy v All subjects
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    Method
    		 Descriptive analysis
    Parameter type
    		 Proportion
    Point estimate
    8.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 38.5
    Notes
    [3] - Overall best tumour response

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From date of consent to 24 months post radiotherapy (90 days to 24 months post radiotherapy: SAR or SUSAR only).
    Adverse event reporting additional description
    The active monitoring period was defined as date of consent to 90 days after the last exposure to radiotherapy. Following this, any SAR or SUSAR were also recorded to the end of trial participation at 24 months post radiotherapy.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.02
    Reporting groups
    Reporting group title
    All subjects
    Reporting group description
    		 All 12 subjects included in the analysis.

    Serious adverse events
    		 All subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 12 (25.00%)
         number of deaths (all causes)
    8
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 All subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 12 (83.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Headache
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Investigations
    Hypomagnesium
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Low potassium
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Mild hypokalaemia
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Mild hypophosphataemia
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Normocytic anaemia
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Mild hyponatraemia
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Suspected fall
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Temperature spike
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Vascular disorders
    Varicose veins
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    5 / 12 (41.67%)
         occurrences all number
    5
    Oral thrush
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Weight loss
         subjects affected / exposed
    2 / 12 (16.67%)
         occurrences all number
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    2 / 12 (16.67%)
         occurrences all number
    2
    Vomiting
         subjects affected / exposed
    2 / 12 (16.67%)
         occurrences all number
    2
    Respiratory, thoracic and mediastinal disorders
    Dry cough
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Pleural effusion
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Arm lymphoedema
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Chronic kidney disease - fluid overload
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    UTI
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Pain
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Infections and infestations
    Sepsis
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1
    Shivery
         subjects affected / exposed
    1 / 12 (8.33%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Nov 2016
    AM1611/21 Addition of exclusion criteria. Addition of tumour tissue collection. Amendment to footnote on contraception.
    02 Mar 2017
    AM1702/57 Error. The protocol was always intended for men as well as women and the title and inclusion criteria have now been corrected accordingly.
    12 Apr 2017
    AM1704/08 Clarification of number of KORTUC injections (6 Fr). Change to stopping rules and withdrawal criteria. Change to inclusion criterion (minimum tumour size).
    12 Apr 2017
    AM1707/42 Change to stopping rules.
    26 Oct 2017
    AM1710/48 Change to eligibility criteria (allowing concomitant Herceptin and Pentuzumab).
    28 Dec 2017
    AM1711/83 Change to eligibility criteria (allowing concomitant Denosumab). Clarification of number of KORTUC injections (18 Fr) List of AEs not to be reported to Sponsor.
    25 Jan 2019
    AM1901/71 Change of Sponsor from The Royal Marsden NHS Foundation Trust to The Institute of Cancer Research.
    25 Feb 2019
    AM1902/43 Addition of 3 time points for the secondary endpoint of tumour control in phase I.

    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.
    None

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/32585332
    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 Apr 19 13:25:32 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA