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    Clinical Trial Results:
    NICO - CA209-891: Neoadjuvant and adjuvant nivolumab as Immune Checkpoint inhibition in Oral cavity cancer

    Summary
    EudraCT number
    		 2017-005015-13
    Trial protocol
    		 GB  
    Global end of trial date
    01 Nov 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Mar 2025
    First version publication date
    13 Mar 2025
    Other versions
    Summary report(s)
    		 NICO Final SAR V1.0.pdf

    Trial information

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    Trial identification
    Sponsor protocol code
    C0947
    Additional study identifiers
    ISRCTN number
    		 ISRCTN17428671
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    The Clatterbridge Cancer Centre NHS Foundation Trust
    Sponsor organisation address
    Clatterbridge Road, Bebington, Wirral, United Kingdom, CH63 4JY
    Public contact
    Dr Maria Maguire, Head of Research Governance and Sponsorship, The Clatterbridge Cancer Centre , +44 7824609720, maria.maguire2@nhs.net
    Scientific contact
    Dr Maria Maguire, Head of Research Governance and Sponsorship, The Clatterbridge Cancer Centre NHS Foundation Trust, +44 7824609720, maria.maguire2@nhs.net
    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
    01 Jul 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Nov 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Nov 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess whether Nivolumab in addition to standard therapy (Surgery followed by radiotherapy or radiotherapy with chemotherapy) leads to a reduction of disease recurrence. Feasibility of recruitment into both cohorts.
    Protection of trial subjects
    Central and site monitoring is conducted to ensure protection of patients participating in the trial, and that trial procedures, trial intervention administration, and laboratory and data collection processes are of high quality and meet sponsor and, when appropriate, regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 May 2019
    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: 23
    Worldwide total number of subjects
    23
    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)
    15
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial opened to recruitment on 08/05/2019. Four centres were opened (one was not a recruiting centre), three in England and one in Scotland.

    Pre-assignment
    Screening details
    		 Potentially eligible patients were assessed at the earliest opportunity following referral of patients with locally advanced oral cavity cancer to trial clinicians.

    Period 1
    Period 1 title
    Main Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Nivolumab
    Arm description
    		 Single dose of nivolumab (240mg flat dose) will be delivered pre-surgery and then between surgery and chemoradiotherapy/radiotherapy. The latter will be followed by six months of adjuvant nivolumab (480mg flat dose every 4 weeks, total of 6 doses). Resection of the tumour, and radiotherapy or chemoradiotherapy will follow standard practice, with patients with high risk features on pathological section (presence of extracapsular spread, involved or positive margins) being assigned to chemoradiation.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single dose of nivolumab (240mg flat dose) will be delivered pre-surgery and then between surgery and chemoradiotherapy/radiotherapy. The latter will be followed by six months of adjuvant nivolumab (480mg flat dose every 4 weeks, total of 6 doses).

    Number of subjects in period 1
    		Nivolumab
    Started
    23
    Completed
    7
    Not completed
    16
         Intolerable Toxicity - colitis
    1
         G1 pneumonitis on imaging, pat didn't wish to cont
    1
         Decision not to have adjuvant treatment
    1
         Immunotherapy related colitis
    1
         Disease status downstaged post operatively
    1
         Moved to different location
    1
         Patient non-compliance
    1
         Fatigue/frustrated with treatment, pat declined
    1
         Perform stat drop, prolonged recovery, pat decline
    1
         Died
    4
         Missing
    2
         Unacceptable blood results prior to first niv
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Main Trial (overall period)
    Reporting group description
    		 -

    Reporting group values
    		 Main Trial (overall period) Total
    Number of subjects
    		 23 23
    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)
    		 15 15
        From 65-84 years
    		 8 8
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 9 9
        Male
    		 14 14
    Smoking status
    Units: Subjects
        Non-smoker
    		 10 10
        Current smoker
    		 7 7
        Ex-smoker
    		 6 6
    Alcohol (units per week)
    Units: Subjects
        0-14 units
    		 15 15
        15-35 units
    		 4 4
        >35 units
    		 4 4
    ECOG
    Units: Subjects
        Zero
    		 19 19
        One
    		 4 4
    Tumour
    Units: Subjects
        T2
    		 2 2
        T3
    		 5 5
        T4
    		 3 3
        T4a
    		 12 12
        T4b
    		 1 1
    Nodes
    Units: Subjects
        N0
    		 5 5
        N1
    		 8 8
        N2b
    		 6 6
        N2c
    		 3 3
        N3b
    		 1 1
    Metastases
    Units: Subjects
        M0
    		 23 23
    Radiological evidence of extra capsular spread
    Units: Subjects
        No
    		 19 19
        Yes
    		 4 4
    Tumour size
    Units: mm^2
        median (inter-quartile range (Q1-Q3))
    		 705.0 (391.0 to 1352.0) -
    Haemoglobin
    Units: g/L
        median (inter-quartile range (Q1-Q3))
    		 136.0 (128.0 to 152.0) -
    WBC
    Units: 10^9/L
        median (inter-quartile range (Q1-Q3))
    		 8.6 (6.6 to 10.4) -
    Neutrophils
    Units: 10^9/L
        median (inter-quartile range (Q1-Q3))
    		 5.7 (4.3 to 7.7) -
    Lymphocytes
    Units: 10^9/L
        median (inter-quartile range (Q1-Q3))
    		 1.8 (1.3 to 2.2) -
    Platelets
    Units: 10^9/L
        median (inter-quartile range (Q1-Q3))
    		 295.0 (259.0 to 365.0) -
    TSH
    Units: mU/L
        median (inter-quartile range (Q1-Q3))
    		 2.2 (1.6 to 3.5) -
    Lipase
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 29.5 (25.0 to 34.0) -
    Amylase
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 58.0 (42.0 to 75.0) -
    Blood glucose
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    		 5.6 (5.1 to 5.9) -
    Sodium
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    		 140.0 (136.0 to 140.0) -
    Potassium
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    		 4.4 (4.2 to 4.9) -
    Calcium (unadjusted)
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    		 2.4 (2.3 to 2.5) -
    Calcium (adjusted)
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    		 2.3 (2.2 to 2.4) -
    Magnesium
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    		 0.8 (0.8 to 0.9) -
    Urea
    Units: mmol/L
        median (inter-quartile range (Q1-Q3))
    		 4.9 (3.7 to 5.6) -
    Creatinine
    Units: μmol/L
        median (inter-quartile range (Q1-Q3))
    		 80.0 (70.0 to 85.0) -
    Creatinine clearance
    Units: ml/min
        median (inter-quartile range (Q1-Q3))
    		 97.3 (74.3 to 119.0) -
    Total bilirubin
    Units: μmol/L
        median (inter-quartile range (Q1-Q3))
    		 8.0 (5.0 to 11.0) -
    Albumin
    Units: g/L
        median (inter-quartile range (Q1-Q3))
    		 44.0 (42.0 to 45.0) -
    ALP
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 73.0 (69.0 to 103.0) -
    AST
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 18.0 (16.0 to 44.0) -
    ALT
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 18.0 (13.0 to 38.0) -
    YGT
    Units: U/L
        median (inter-quartile range (Q1-Q3))
    		 44.5 (19.0 to 138.5) -
    Age continuous
    Units: Years
        median (inter-quartile range (Q1-Q3))
    		 62.0 (47.0 to 66.0) -

    End points

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    End points reporting groups
    Reporting group title
    Nivolumab
    Reporting group description
    		 Single dose of nivolumab (240mg flat dose) will be delivered pre-surgery and then between surgery and chemoradiotherapy/radiotherapy. The latter will be followed by six months of adjuvant nivolumab (480mg flat dose every 4 weeks, total of 6 doses). Resection of the tumour, and radiotherapy or chemoradiotherapy will follow standard practice, with patients with high risk features on pathological section (presence of extracapsular spread, involved or positive margins) being assigned to chemoradiation.

    Primary: One year disease-free survival rate

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    End point title
    		 One year disease-free survival rate [1]
    End point description
    End point type
    Primary
    End point timeframe
    Probability of disease-free survival at 12 months following surgery
    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: Due to the trial being stopped early, there was no statistical analyses conducted.
    End point values
    		 Nivolumab
    Number of subjects analysed
    20 [2]
    Units: Probability
        number (confidence interval 95%)
    0.84 (0.59 to 0.95)
    Notes
    [2] - All participants who had surgery
    No statistical analyses for this end point

    Secondary: Surgical complications - surgical site infection

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    End point title
    		 Surgical complications - surgical site infection
    End point description
    End point type
    Secondary
    End point timeframe
    Surgical site infection following trial surgery
    End point values
    		 Nivolumab
    Number of subjects analysed
    20 [3]
    Units: Surgical site infection rate
        number (confidence interval 95%)
    0.26 (0.09 to 0.51)
    Notes
    [3] - All participants who had surgery
    No statistical analyses for this end point

    Secondary: Surgical complications - other infection

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    End point title
    		 Surgical complications - other infection
    End point description
    End point type
    Secondary
    End point timeframe
    Other infection post trial surgery
    End point values
    		 Nivolumab
    Number of subjects analysed
    20 [4]
    Units: Other infection rate
        number (confidence interval 95%)
    0.32 (0.13 to 0.57)
    Notes
    [4] - All participants who had surgery
    No statistical analyses for this end point

    Secondary: Surgical complications - length of hospital admission

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    End point title
    		 Surgical complications - length of hospital admission
    End point description
    End point type
    Secondary
    End point timeframe
    Length of hospital admission post trial surgery
    End point values
    		 Nivolumab
    Number of subjects analysed
    19 [5]
    Units: Days
        arithmetic mean (confidence interval 95%)
    13.21 (10.05 to 16.37)
    Notes
    [5] - All participants who had surgery and are not missing discharge dates
    No statistical analyses for this end point

    Secondary: Surgical complications - free flap failure &/or compromise

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    End point title
    		 Surgical complications - free flap failure &/or compromise
    End point description
    End point type
    Secondary
    End point timeframe
    Free flap failure &/or compromise post trial surgery
    End point values
    		 Nivolumab
    Number of subjects analysed
    20 [6]
    Units: Free flap failure &/or compromise rate
        number (confidence interval 95%)
    0.11 (0.01 to 0.33)
    Notes
    [6] - All participants who had surgery
    No statistical analyses for this end point

    Secondary: Surgical complications - perioperative (30-day) mortality

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    End point title
    		 Surgical complications - perioperative (30-day) mortality
    End point description
    End point type
    Secondary
    End point timeframe
    Perioperative (30-day) mortality post surgery
    End point values
    		 Nivolumab
    Number of subjects analysed
    20 [7]
    Units: Perioperative (30-day) mortality rate
        number (confidence interval 95%)
    0.05 (0.00 to 0.25)
    Notes
    [7] - All participants who had surgery
    No statistical analyses for this end point

    Secondary: Quality of life - EORTC QLQ-C30

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    End point title
    		 Quality of life - EORTC QLQ-C30
    End point description
    End point type
    Secondary
    End point timeframe
    Change from baseline to end of treatment
    End point values
    		 Nivolumab
    Number of subjects analysed
    11 [8]
    Units: Change from baseline in score
    arithmetic mean (confidence interval 95%)
        Global health status/QoL
    -0.76 (-18.72 to 17.20)
        Physical Functioning
    -13.33 (-27.78 to 1.11)
        Role Functioning
    -12.12 (-35.12 to 10.88)
        Emotional Functioning
    11.36 (-0.45 to 23.18)
        Cognitive Functioning
    -6.06 (-15.12 to 3.00)
        Social Functioning
    -12.12 (-27.22 to 2.98)
        Fatigue
    12.12 (-11.12 to 35.36)
        Nausea and Vomiting
    -1.52 (-13.21 to 10.18)
        Pain
    -12.12 (-34.00 to 9.76)
        Dyspnoea
    9.09 (-8.52 to 26.70)
        Insomnia
    6.06 (-21.94 to 34.06)
        Appetite Loss
    6.06 (-26.88 to 39.00)
        Constipation
    9.09 (-15.63 to 33.81)
        Diarrhoea
    3.03 (-9.05 to 15.11)
        Financial Difficulties
    3.03 (-15.58 to 21.64)
    Notes
    [8] - All participants with both baseline and end of treatment questionnaires
    No statistical analyses for this end point

    Secondary: Quality of life - EORTC QLQ-H&N35

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    End point title
    		 Quality of life - EORTC QLQ-H&N35
    End point description
    End point type
    Secondary
    End point timeframe
    Change in quality of life from baseline to end of treatment
    End point values
    		 Nivolumab
    Number of subjects analysed
    10 [9]
    Units: Change from baseline score
    arithmetic mean (confidence interval 95%)
        Pain
    -13.33 (-29.53 to 2.86)
        Swallowing
    -0.83 (-25.56 to 23.90)
        Senses problems
    10.00 (-7.95 to 27.95)
        Speech problems
    8.89 (-4.52 to 22.29)
        Trouble with social eating
    18.33 (-6.13 to 42.80)
        Trouble with social contact
    22.67 (7.39 to 37.95)
        Less sexuality
    10.00 (-21.39 to 41.39)
        Teeth
    10.00 (-12.62 to 32.62)
        Opening mouth
    -3.33 (-31.88 to 25.21)
        Dry mouth
    13.33 (-6.77 to 33.44)
        Sticky saliva
    0.00 (-19.47 to 19.47)
        Coughing
    16.67 (-6.51 to 39.84)
        Felt ill
    6.67 (-22.65 to 35.98)
    Notes
    [9] - All participants with baseline and end of treatment questionnaires
    No statistical analyses for this end point

    Secondary: Quality of life - EORTC QLQ-H&N35 binary items

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    End point title
    		 Quality of life - EORTC QLQ-H&N35 binary items
    End point description
    End point type
    Secondary
    End point timeframe
    Change in quality of life from baseline to end of treatment
    End point values
    		 Nivolumab
    Number of subjects analysed
    10 [10]
    Units: Participants
        Painkillers Yes-Yes
    5
        Painkillers Yes-No
    5
        Nutritional supplements (exc vitamins) Yes-Yes
    3
        Nutritional supplements (exc vitamins) No-Yes
    3
        Nutritional supplements (exc vitamins) No-No
    4
        Feeding tube No-Yes
    1
        Feeding tube No-No
    9
        Lost weight Yes-Yes
    1
        Lost weight Yes-No
    2
        Lost weight No-Yes
    2
        Lost weight No-No
    5
        Gained weight Yes-Yes
    2
        Gained weight Yes-No
    1
        Gained weight No-Yes
    4
        Gained weight No-No
    3
    Notes
    [10] - All participants with baseline and end of treatment questionnaires
    No statistical analyses for this end point

    Secondary: Disease-free survival

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    End point title
    		 Disease-free survival
    End point description
    End point type
    Secondary
    End point timeframe
    Measured as time from surgery until disease recurrence or death. The survival probability never goes below 0.5 so no median is able to be presented.
    End point values
    		 Nivolumab
    Number of subjects analysed
    20 [11]
    Units: Participants
        Experienced disease recurrence or death
    4
        Did not experience disease recurrence or death
    16
    Notes
    [11] - All participants who had surgery
    No statistical analyses for this end point

    Secondary: Overall survival

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    End point title
    		 Overall survival
    End point description
    End point type
    Secondary
    End point timeframe
    Measured as time from recruitment until death. The survival probability never goes below 0.5 so a median is not presented.
    End point values
    		 Nivolumab
    Number of subjects analysed
    23 [12]
    Units: Participants
        Experienced death
    4
        Did not experience death
    19
    Notes
    [12] - All participants
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    New AEs that occurred following consent and up to 100 days post last dose of trial treatment needed to be recorded. In other situations, medical and scientific judgement were exercised to decide if expedited reporting was appropriate.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24
    Reporting groups
    Reporting group title
    Safety
    Reporting group description
    		 Participants had to have had at least once dose of Nivolumab.

    Serious adverse events
    		 Safety
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 22 (36.36%)
         number of deaths (all causes)
    4
         number of deaths resulting from adverse events
    1
    Cardiac disorders
    Heart failure
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Oral haemorrhage
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic epidermal necrolysis
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Confusion
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Head soft tissue necrosis
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Bronchial infection
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulitis intestinal perforated
         subjects affected / exposed
    1 / 22 (4.55%)
         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
    		 Safety
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 22 (86.36%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Fatigue
         subjects affected / exposed
    5 / 22 (22.73%)
         occurrences all number
    5
    Fever
         subjects affected / exposed
    4 / 22 (18.18%)
         occurrences all number
    2
    Mucositis
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Oedema
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Pain
         subjects affected / exposed
    13 / 22 (59.09%)
         occurrences all number
    11
    Respiratory, thoracic and mediastinal disorders
    Sore throat
         subjects affected / exposed
    6 / 22 (27.27%)
         occurrences all number
    6
    Pneumonia
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Pneumonitis
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    3 / 22 (13.64%)
         occurrences all number
    3
    Investigations
    Creatinine increased
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Thyroid stim. hormone increased
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    WBC decreased
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Weight loss
         subjects affected / exposed
    12 / 22 (54.55%)
         occurrences all number
    11
    Injury, poisoning and procedural complications
    Dermatitis radiation
         subjects affected / exposed
    11 / 22 (50.00%)
         occurrences all number
    10
    Incisional hernia
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Cardiac disorders
    Left bundle branch block
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Right bundle branch block
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Sinus tachycardia
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    6 / 22 (27.27%)
         occurrences all number
    6
    Lethargy
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Colitis
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Constipation
         subjects affected / exposed
    6 / 22 (27.27%)
         occurrences all number
    6
    Diarrhoea
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Dry mouth
         subjects affected / exposed
    6 / 22 (27.27%)
         occurrences all number
    6
    Dysphagia
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Mucositis oral
         subjects affected / exposed
    17 / 22 (77.27%)
         occurrences all number
    13
    Nausea
         subjects affected / exposed
    8 / 22 (36.36%)
         occurrences all number
    8
    Oral pain
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Proctitis
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Vomiting
         subjects affected / exposed
    7 / 22 (31.82%)
         occurrences all number
    5
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Erythema
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Maculopapular rash
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Skin disorder
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Chronic kidney disease
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Hyperthyroidism
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    1
    Hypothyroidism
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Lung infection
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Throat infection
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Upper respiratory infection
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Urinary tract infection
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Wound infection
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    3 / 22 (13.64%)
         occurrences all number
    3
    Dehydration
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Hyperkalemia
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Hypocalcaemia
         subjects affected / exposed
    3 / 22 (13.64%)
         occurrences all number
    3
    Hypoglycaemia
         subjects affected / exposed
    1 / 22 (4.55%)
         occurrences all number
    1
    Hypomagnesemia
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    1
    Hyponatraemia
         subjects affected / exposed
    2 / 22 (9.09%)
         occurrences all number
    2
    Hypophosphatemia
         subjects affected / exposed
    3 / 22 (13.64%)
         occurrences all number
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jul 2019
    Update of PIs at sites. Addition of new sites. Update of RSI and IB
    08 Aug 2019
    Addition of 4 new sites
    29 Jul 2020
    Dear Patient and Dear Investigator Letters prepared in response to NICO re-opening and lifting the pause in recruitment due to COVID-19 NIHR issued guidance for consideration towards restarting projects (see Annex A https://www.nihr.ac.uk/documents/restart-framework/24886) NICO re-start followed this framework.
    13 Aug 2020
    Substantial amendment to the Protocol, PIS and ICF to include: 1. Update to Reference Safety Information following Investigator Brochure update. 2. Trial Treatment: Time to adjuvant Nivolumab extended from 6 weeks to 10 weeks 3. Change to follow up scan times from 4 months to 6, 9, 12 to ensure scans are outside of treatment window 4. Chemo/Radiotherapy updated to clarify any patient experiencing an 8 week or greater interval between surgery and commencement of radiotherapy/chemoradiotherapy will be withdrawn from the trial. 5. Translational Research Sub-studies: a) faecal and oral microbiome samples and b) imaging 6. Translational samples: increase amount of blood sample as original bloods insufficient for testing / maximise opportunities 7. Ethical Considerations: Update to include GDPR requirements Luton & Dunstable Site added
    06 Nov 2020
    Addition 3 New sites: The Walton Centre (MRI sub-study site) East Lancashire Hospital Trust (ELHT) (Royal Blackburn Teaching Hospital) Cambridge University Hospital Trust (Addenbrooke's Hospital)
    11 Feb 2021
    Early Termination by funder (MS) Protocol update & Dear Patient Letter/reconsent

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    26 Oct 2020
    On 26/10/2020, the study funder wrote to the Chief Investigator and Study Sponsor to terminate the Investigator-Sponsor Research Agreement. The termination allowed the continued registration of new patients up to 30 days from the date of the letter of termination. All study recruitment was ceased by 25/11/2020.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    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.

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