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   43845   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:
    XERXES: Examining the role of early neoadjuvant and synchronous Erbitux in pre-operative chemo-radiotherapy using Xeloda followed by excisional surgery. A phase I/II dose escalation study of intravenous erbitux (cetuximab) in combination with 5 day weekly oral Xeloda (capecitabine) and preoperative radiotherapy in rectal cancer.

    Summary
    EudraCT number
    		 2004-001926-26
    Trial protocol
    		 GB  
    Global end of trial date
    30 Nov 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Dec 2016
    First version publication date
    11 Dec 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    XERXES
    Additional study identifiers
    ISRCTN number
    		 ISRCTN11319909
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 MHRA CTA No.: 20363/0205/001
    Sponsors
    Sponsor organisation name
    University College London
    Sponsor organisation address
    Joint Research Office, Gower Street, London, United Kingdom, WC1E 6BT
    Public contact
    ctc.sponsor@ucl.ac.uk, CR UK & UCL Cancer Trials Centre, ctc.sponsor@ucl.ac.uk
    Scientific contact
    ctc.sponsor@ucl.ac.uk, CR UK & UCL Cancer Trials Centre, ctc.sponsor@ucl.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
    30 Nov 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Nov 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Nov 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the safety and toxicity of the combination of erbitux, capecitabine and radiotherapy. This will be determined through an assessment of the patient’s toxicity
    Protection of trial subjects
    UCL CTC provided safety information to the TMG on a periodic basis for review. Trial safety data was monitored to identify: • New adverse reactions to the trial treatment regimen or individual trial treatments; • A higher incidence in rare adverse events than is stated in the IB/SPC for a trial treatment; • Trial related events that are not considered related to the trial treatment regimen. Should UCL CTC have identified or suspected any issues concerning patient safety at any point throughout the trial, the CI or TMG would have been consulted for their opinion.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jul 2005
    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
    United Kingdom: 22
    Worldwide total number of subjects
    22
    EEA total number of subjects
    22
    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)
    13
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 12 patients were entered into phase 1 of the trial receiving Cetuximab prior to chemoradiation (Cisplatin). 10 patient's were entered into phase 2, with 5 patient's randomised to Arm A (Capecitabine and radiotherapy) and 5 randomised to Arm B (Cetuximab, capecitabine and radiotherapy). Recruitment spanned 01/07/05 - 01/10/12 at UK sites.

    Pre-assignment
    Screening details
    		 Screening details: All eligibility criteria were based on routine tests and investigations.

    Period 1
    Period 1 title
    Phase 1
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Phase 1
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400mg/m2 in a short iv infusion as a starting dose then a weekly dose of 250mg/m2 for 4 weeks prior to Chemoradiation (days 3, 10, 17, 24).

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral capecitabine 825 mg/m2 twice daily for 5 days in weeks 5-9

    Number of subjects in period 1
    		Phase 1
    Started
    12
    Completed
    12
    Period 2
    Period 2 title
    Phase 2
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A
    Arm description
    		 Capecitabine and radiotherapy
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    825 mg/m2 twice daily for 5 days in weeks 1-5

    Arm title
    		 Arm B
    Arm description
    		 Cetuximab, capecitabine and radiotherapy
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400mg/m2 in a short iv infusion as a starting dose prior to chemoradiation in weeks 1-4, and then a weekly dose of 250mg/m2 for 4 weeks after chemoradiation in weeks 10-14.

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral capecitabine 825 mg/m2 twice daily weeks 5-9

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: There are 2 Baseline periods (Phase 1 and Phase 2) as two separate subsets of patients were recruited into both.
    Number of subjects in period 2 [2] [3]
    		Arm A Arm B
    Started
    5
    5
    Completed
    5
    4
    Not completed
    0
    1
         Consent withdrawn by subject
    -
    1
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: There are 2 Baseline periods (Phase 1 and Phase 2) as two separate subsets of patients were recruited into both.
    [3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The Phase 1 and Phase 2 periods are not separate treatment periods but different periods in the trial. There is a separate group of patients recruited into each Phase. (i.e 12 patients in Phase 1, 10 patients in Phase 2)

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Capecitabine and radiotherapy

    Reporting group title
    Arm B
    Reporting group description
    		 Cetuximab, capecitabine and radiotherapy

    Reporting group values
    		 Arm A Arm B Total
    Number of subjects
    		 5 5 10
    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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 61.69 (57.34 to 78.22) 63.04 (53.97 to 69.33) -
    Gender categorical
    Units: Subjects
        Female
    		 2 2 4
        Male
    		 3 3 6
    Nodal status
    Units: Subjects
        N0
    		 0 1 1
        N1
    		 4 2 6
        N2
    		 1 2 3
        NX
    		 0 0 0
    WHO performance status
    Units: Subjects
        WHO 0
    		 3 4 7
        WHO 1
    		 2 0 2
        Not Reported
    		 0 1 1
    Site of tumour
    Units: Subjects
        Anterior
    		 1 1 2
        Posterior
    		 0 2 2
        Not known
    		 4 2 6
    Site
    Units: Subjects
        Lower (0 - 4.9cm)
    		 2 2 4
        Middle (5 - 9.9cm)
    		 3 2 5
        Upper (10 - 15cm)
    		 0 1 1
    Tumour stage
    Units: Subjects
        Tumour beyond mesorectal fascia
    		 1 0 1
        Tumour ≤ 2mm from mesorectal fascia
    		 1 1 2
        T3/T4 tumour ≤ 5cm from the anal verge
    		 3 4 7
    Glomerular filtration rate (GFR) (EDTA)
    Units: ml/min
        median (full range (min-max))
    		 75 (54 to 143) 84 (67 to 90) -
    Absolute Neutrophil Count (ANC)
    Units: x109/L
        median (full range (min-max))
    		 6.4 (3.5 to 11.3) 5.7 (2.3 to 8.2) -
    Platelets
    Units: x109/L
        median (full range (min-max))
    		 286 (247 to 535) 277 (253 to 383) -
    Bilirubin
    Units: μmol/L
        median (full range (min-max))
    		 10 (6 to 17) 6 (4 to 9) -
    Alk. Phosphatase
    Units: IU/L
        median (full range (min-max))
    		 77 (44 to 108) 72 (66 to 94) -
    Alanine Transaminase (ALT)
    Units: IU/L
        median (full range (min-max))
    		 22 (20 to 29) 19 (8 to 22) -
    CEA
    Units: μg/l
        median (full range (min-max))
    		 -
    White Blood Cells
    Units: x109/l
        median (full range (min-max))
    		 -
    Haemoglobin
    Units: g/dl
        median (full range (min-max))
    		 -
    Magnesium
    Units: mmol/l
        median (full range (min-max))
    		 -
    Subject analysis sets

    Subject analysis set title
    Phase 1
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Analysis for Phase 1 section of the trial carried out separately to Phase 2.

    Subject analysis sets values
    		 Phase 1
    Number of subjects
    12
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        median (full range (min-max))
    65 (29 to 76)
    Gender categorical
    Units: Subjects
        Female
    1
        Male
    11
    Nodal status
    Units: Subjects
        N0
    2
        N1
    4
        N2
    4
        NX
    2
    WHO performance status
    Units: Subjects
        WHO 0
    7
        WHO 1
    5
        Not Reported
    0
    Site of tumour
    Units: Subjects
        Anterior
        Posterior
        Not known
    Site
    Units: Subjects
        Lower (0 - 4.9cm)
    4
        Middle (5 - 9.9cm)
    7
        Upper (10 - 15cm)
    1
    Tumour stage
    Units: Subjects
        Tumour beyond mesorectal fascia
    3
        Tumour ≤ 2mm from mesorectal fascia
    5
        T3/T4 tumour ≤ 5cm from the anal verge
    7
    Glomerular filtration rate (GFR) (EDTA)
    Units: ml/min
        median (full range (min-max))
    89.3 (51.08 to 132)
    Absolute Neutrophil Count (ANC)
    Units: x109/L
        median (full range (min-max))
    4.96 (3.29 to 6.21)
    Platelets
    Units: x109/L
        median (full range (min-max))
    306 (221 to 420)
    Bilirubin
    Units: μmol/L
        median (full range (min-max))
    Alk. Phosphatase
    Units: IU/L
        median (full range (min-max))
    Alanine Transaminase (ALT)
    Units: IU/L
        median (full range (min-max))
    CEA
    Units: μg/l
        median (full range (min-max))
    3 (1 to 45)
    White Blood Cells
    Units: x109/l
        median (full range (min-max))
    7.68 (5.88 to 9.48)
    Haemoglobin
    Units: g/dl
        median (full range (min-max))
    13.45 (9.9 to 133)
    Magnesium
    Units: mmol/l
        median (full range (min-max))
    0.88 (0.82 to 0.92)

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Phase 1
    Reporting group description
    		 -
    Reporting group title
    Arm A
    Reporting group description
    		 Capecitabine and radiotherapy

    Reporting group title
    Arm B
    Reporting group description
    		 Cetuximab, capecitabine and radiotherapy

    Subject analysis set title
    Phase 1
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Analysis for Phase 1 section of the trial carried out separately to Phase 2.

    Primary: Acute Toxicity (Grade 3 or above in defined DLT)

    		 Close Top of page
    End point title
    		 Acute Toxicity (Grade 3 or above in defined DLT) [1]
    End point description
    End point type
    Primary
    End point timeframe
    Phase 1 and Phase 2
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The statistics provided are descriptive only. No mathematical statistical analysis was carried out.
    End point values
    		 Arm A Arm B Phase 1
    Number of subjects analysed
    5
    5
    12
    Units: Worst adverse event experienced
        Pain Grade 3
    0
    0
    1
        Pulmonary embolism Grade 3
    0
    0
    1
        Rash acneiform Grade 3
    0
    0
    2
        Diarrhea Grade 3
    1
    0
    0
    No statistical analyses for this end point

    Primary: Compliance with the planned dose of radiotherapy

    		 Close Top of page
    End point title
    		 Compliance with the planned dose of radiotherapy [2]
    End point description
    End point type
    Primary
    End point timeframe
    Phase 1 and Phase 2 Treatment
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The statistics provided are descriptive only. No mathematical statistical analysis was carried out.
    End point values
    		 Arm A Arm B Phase 1
    Number of subjects analysed
    5
    4
    12
    Units: Patients
        Irradiation temporarily interrupted (Yes)
    3
    1
    1
        Irradiation temporarily interrupted (No)
    2
    3
    11
        Reasons for interruption - (Bank Holiday)
    1
    1
    1
        Reasons for interruption - (Intercurrent Illness)
    1
    0
    0
        Reasons for interruption - (Toxicity)
    1
    0
    0
        Irradiation stopped early (No)
    5
    4
    12
        Irradiation stopped early (Yes)
    0
    0
    0
        Total dose given at ICRU reference (45)
    5
    4
    12
        Number of Fractions (25)
    5
    4
    12
    No statistical analyses for this end point

    Primary: Compliance with the planned dose of chemotherapy - Capecitabine compliance

    		 Close Top of page
    End point title
    		 Compliance with the planned dose of chemotherapy - Capecitabine compliance [3]
    End point description
    End point type
    Primary
    End point timeframe
    Phase 1 and Phase 2 treatment
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The statistics provided are descriptive only. No mathematical statistical analysis was carried out.
    End point values
    		 Arm A Arm B Phase 1
    Number of subjects analysed
    5
    4
    12
    Units: Patients
        Reductions of capecitabine
    1
    0
    0
        Capecitabine Adminitration Delays
    3
    0
    1
        Any missed tablets
    6
    1
    2
        Capecitabine stopped permanently
    0
    0
    1
    No statistical analyses for this end point

    Primary: Histopathological complete response rate

    		 Close Top of page
    End point title
    		 Histopathological complete response rate [4]
    End point description
    End point type
    Primary
    End point timeframe
    Phase 1 and Phase 2
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The statistics provided are descriptive only. No mathematical statistical analysis was carried out.
    End point values
    		 Arm A Arm B Phase 1
    Number of subjects analysed
    5
    5
    12
    Units: Patients
        Complete response
    1
    1
    0
        Partial response
    3
    2
    10
        Stable disease
    1
    1
    2
        Not done
    0
    1
    0
    No statistical analyses for this end point

    Primary: Compliance with the planned dose of chemotherapy - Cetuximab Compliance

    		 Close Top of page
    End point title
    		 Compliance with the planned dose of chemotherapy - Cetuximab Compliance [5] [6]
    End point description
    End point type
    Primary
    End point timeframe
    Phase 1 and Phase 2 treatment
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The statistics provided are descriptive only. No mathematical statistical analysis was carried out.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Compliance to cetuximab is only applicable to one arm as the other arm were not given cetuximab.
    End point values
    		 Arm B Phase 1
    Number of subjects analysed
    4
    12
    Units: Patients
        Reductions
    0
    0
        Delays
    1
    2
        Stopping permanently
    0
    1
    No statistical analyses for this end point

    Secondary: Histopathological downstaging (yPT0,T1,T2 N0) - Phase 2

    		 Close Top of page
    End point title
    		 Histopathological downstaging (yPT0,T1,T2 N0) - Phase 2
    End point description
    End point type
    Secondary
    End point timeframe
    Phase 2 Surgery
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    4
    3
    Units: Patients
        T restaging - T2 -> T0
    1
    0
        T restaging - T3 -> T0
    0
    1
        T restaging - T2 -> T1
    0
    1
        T restaging - T3 -> T2
    1
    0
        T restaging - T3 -> T3
    2
    1
        Regression - No tumour present
    1
    2
        Regression - Few tumour cells
    1
    1
        Regression - Moderate
    1
    0
        Regression - Mild
    1
    0
        N restaging - N0 -> N2
    0
    1
        N restaging - N1 -> N0
    3
    2
        N restaging - N1 -> N2
    1
    0
    No statistical analyses for this end point

    Secondary: Histologically confirmed (R0) resection

    		 Close Top of page
    End point title
    		 Histologically confirmed (R0) resection
    End point description
    End point type
    Secondary
    End point timeframe
    Phase 1 and Phase 2 Surgery
    End point values
    		 Arm A Arm B Phase 1
    Number of subjects analysed
    4
    3
    12
    Units: Patients
        R0
    4
    1
    8
        R1
    0
    2
    1
        R2
    0
    0
    1
        Not Reported
    0
    0
    2
    No statistical analyses for this end point

    Secondary: Surgical complications at 1 month

    		 Close Top of page
    End point title
    		 Surgical complications at 1 month
    End point description
    End point type
    Secondary
    End point timeframe
    Phase 2
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    4
    3
    Units: Event
        Anal pain Grade 1
    0
    1
        Hypotension Grade 1
    0
    1
        Vomiting Grade 1
    1
    0
        Rectal Pain Grade 1
    1
    0
        Rectal pain Grade 2
    0
    1
        Constipation Grade 1
    1
    0
        Diarrhea Grade 2
    1
    0
        Fatigue Grade 1
    2
    0
    No statistical analyses for this end point

    Secondary: Histopathological downstaging (yPT0,T1,T2 N0) - Phase 1

    		 Close Top of page
    End point title
    		 Histopathological downstaging (yPT0,T1,T2 N0) - Phase 1
    End point description
    End point type
    Secondary
    End point timeframe
    Phase 1 Surgery
    End point values
    		 Phase 1
    Number of subjects analysed
    12
    Units: Patients
        Few tumour cells
    3
        Mild
    4
        Moderate
    2
        No tumour present
    1
        Unknown
    2
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Phase 1 and Phase 2
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    Phase 2 - Arm A
    Reporting group description
    		 Capecitabine and radiotherapy

    Reporting group title
    Phase 2 - Arm B
    Reporting group description
    		 Cetuximab, capecitabine and radiotherapy

    Reporting group title
    Phase 1
    Reporting group description
    		 -

    Serious adverse events
    		 Phase 2 - Arm A Phase 2 - Arm B Phase 1
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 5 (40.00%)
    0 / 5 (0.00%)
    4 / 12 (33.33%)
         number of deaths (all causes)
    1
    0
    4
         number of deaths resulting from adverse events
    Vascular disorders
    Thromboembolic event
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusion
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Skin infection
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Phase 2 - Arm A Phase 2 - Arm B Phase 1
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 5 (100.00%)
    5 / 5 (100.00%)
    12 / 12 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    5 / 5 (100.00%)
    4 / 5 (80.00%)
    12 / 12 (100.00%)
         occurrences all number
    5
    4
    12
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Pain
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 5 (20.00%)
    8 / 12 (66.67%)
         occurrences all number
    1
    1
    8
    Fever
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Other: Hand/foot problem (not specified)
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    8 / 12 (66.67%)
         occurrences all number
    0
    0
    8
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    3 / 12 (25.00%)
         occurrences all number
    0
    1
    3
    Respiratory, thoracic and mediastinal disorders
    Dyspnea
         subjects affected / exposed
    2 / 5 (40.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Sore throat
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Cough
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    2
    Hiccups
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Other: Pulmonary embolism
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Confusion
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 5 (40.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 5 (40.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    GGT increased
         subjects affected / exposed
    3 / 5 (60.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    3
    1
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 5 (40.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    0
    Other Investigations
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    White blood cell decreased
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 5 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    1
    Injury, poisoning and procedural complications
    Dermatitis radiation
         subjects affected / exposed
    2 / 5 (40.00%)
    2 / 5 (40.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    2
    0
    Other: Moist desquamation
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 5 (40.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    Headache
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 5 (40.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Paresthesia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 5 (40.00%)
    1 / 5 (20.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    1
    2
    Ear and labyrinth disorders
    Other Ear and labyrinth disorders
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Eye disorders
    Blurred vision
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Eye pain
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Other eye disorders
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    4 / 5 (80.00%)
    5 / 5 (100.00%)
    10 / 12 (83.33%)
         occurrences all number
    4
    5
    10
    Anal haemorrhage
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Anal pain
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 5 (40.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    0
    Constipation
         subjects affected / exposed
    2 / 5 (40.00%)
    3 / 5 (60.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    3
    2
    Mucositis oral
         subjects affected / exposed
    2 / 5 (40.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    Nausia
         subjects affected / exposed
    2 / 5 (40.00%)
    3 / 5 (60.00%)
    6 / 12 (50.00%)
         occurrences all number
    2
    3
    6
    Oral Pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Proctitis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Rectal pain
         subjects affected / exposed
    2 / 5 (40.00%)
    2 / 5 (40.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    2
    0
    Vomiting
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    1
    0
    2
    Abdominal Pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    2
    Dry mouth
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    2
    Dyspepsia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    2
    Other: Oedema
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    2
    Other: PR mucinous
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Other: Rectal discharge
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Other: stomatitis/mucositis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    6 / 12 (50.00%)
         occurrences all number
    0
    0
    6
    Rectal hemorrhage
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    2 / 5 (40.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    Pain of skin
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    1
    Palmar-plantar erythrodysesthesia syndrome
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    Rash acneiform
         subjects affected / exposed
    0 / 5 (0.00%)
    4 / 5 (80.00%)
    12 / 12 (100.00%)
         occurrences all number
    0
    4
    12
    Scalp Pain
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 5 (40.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    Other: Brittle Nails
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Erythema multiforme
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Other: Cracked thumbs
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Other: Nail changes
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Other: Pruritis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    5 / 12 (41.67%)
         occurrences all number
    0
    0
    5
    Other: Skin disorder not specified
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Renal and urinary disorders
    Cystitis noninfective
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Other Renal and urinary disorders
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 5 (40.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    2
    0
    Other: Dysuria
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 5 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    0
    Pain in extremity
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Other: Lower back weakness
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    Infections and infestations
    Nail infection
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Paronychia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    1
    Other Infection
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    2 / 5 (40.00%)
    2 / 5 (40.00%)
    1 / 12 (8.33%)
         occurrences all number
    2
    2
    1
    Hypermagnesemia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    Hypoalbuminemia
         subjects affected / exposed
    2 / 5 (40.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    0
    Hypomagnesemia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Oct 2005
    Update to protocol to v1.1. Amednemnts to sections 1.1 Flowchart, 3.3 End points, 6.2 Pre-treatment, 6.3 cetuximab, 6.6 Treatment modifications, 8.1 Assessments and procedures during treatment, 11.3 Sponsorship & indemnity, 14.3 Schedule of tissue collection, Appendix 3 preparation & handling of cetuximab, Appendix 5 Treatment modifications for toxicity, Appendix 8 summary of investigations
    02 May 2008
    Update to protocol v2.0. Updated contact details, Updated version numbers and dates, updated list of expected toxicities & updated Pharmacovigilance section
    05 Nov 2009
    Update to the protocol to v3.0 and update to Patient Information Sheet and Consent form. Updates to protocol - Minor corrections and changes to improve clarity, change in statistician, change in laboratory storing samples & NCI-CTCAE changed from v3.0 to v4.0, Tumour response assessed at 3-5 wks changed to 5-9 weeks to concur with section 8.2, Radiotherapy regimen for Arm A added as this was mistakenly omitted in previous amendment, Pharmacovigilance section amended to comply with updated regulations, Frequency of CRF completion during treatment reduced, Clarification and addition to the statistics section, Additional serum samples – weekly during chemoradiation & Use of RNAlater rather than liquid nitrogen for fresh tissue biopsies, Updated with relevant AEs from NCI-CTCAE v4.0
    04 May 2010
    Minor update to consent form to change the version and date of the patient information sheet that the patient has confirms they have read.
    07 Dec 2010
    Update to the patient diary cards to v2.0 to reflect the changes made when Protocol v3.0 was updated in Amendment 3
    07 Dec 2010
    Duplicated submission of Amendment 5 in error
    08 Apr 2011
    Change of Principle Investigator at Velindre Cancer Centre
    21 Aug 2012
    Updates to CTA: Change of Sponsor contact details (title, address, telephone and email), amending errors to cetuximab's brand/generic name, amending the Manufacturing Authorisation number, amendment to information concerning the modification of IMP at site.
    17 Dec 2012
    Update to protocol v4.0. Update of trial management staff, Additional section added to include information on Data Management Guidelines, Amended information within Pharmacovigilance section to reflect the most up to date protocol template, additional section added to include information on Incident reporting and Serious breaches, Additional section added to include information on Trial Monitoring and Oversight, Additional section added to reflect current protocol template, and to amend end of trial definition, Expected Adverse Events updated, Protocol history moved from page 1.
    02 Jul 2014
    site closure notification of Leeds, Beatson, Velindre & Aberdeen.

    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 reported
    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 03:45:24 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA