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    Clinical Trial Results:
    A Randomized Phase II Trial for Patients with p16 Positive, Non-Smoking Associated, Locoregionally Advanced Oropharyngeal Cancer

    Summary
    EudraCT number
    		 2016-002244-16
    Trial protocol
    		 IE  
    Global end of trial date

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Jan 2025
    First version publication date
    26 Jan 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    NRG-HN002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02254278
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Cancer Trials Ireland
    Sponsor organisation address
    RCSI House, Dublin, Ireland, D02 H903
    Public contact
    Clinical Program Leader , Irish Clinical Oncology Research Group CLG, trading as Cancer Trials Ireland, +353 16677211, info@cancertrials.ie
    Scientific contact
    Clinical Program Leader , Irish Clinical Oncology Research Group CLG, trading as Cancer Trials Ireland, 0876654933 16677211, info@cancertrials.ie
    Sponsor organisation name
    NRG Oncology
    Sponsor organisation address
    1818 Market Street, Suite 1720, Philadelphia, United States, PA 19103
    Public contact
    Clinical Project Manager, NRG Oncology, +1 267-519-6630, info@nrgoncology.org
    Scientific contact
    Clinical Project Manager, NRG Oncology, +1 267-519-6630, info@nrgoncology.org
    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
    Interim
    Date of interim/final analysis
    25 Jun 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Jun 2019
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To select the arm(s) achieving a 2-year progression-free survival rate of >= 85% without unacceptable swallowing toxicity at 1 year.
    Protection of trial subjects
    The Trial was conducted in accordance with International Conference on Harmonization Good Clinical Practice Guidelines and principles of the Declaration of Helsinki of 1964. An independent, unblinded data and safety monitoring committee reviewed safety and efficacy data at predefined data points. Patients provided written informed consent before undergoing any trial-related procedures.
    Background therapy
    		 None
    Evidence for comparator
    		 This randomized phase II trial studies the side effects and how well modestly reduced-dose intensity-modulated radiation therapy (IMRT) with or without cisplatin works in treating patients with oropharyngeal cancer that has spread to other places in the body (advanced). Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether IMRT is more effective with or without cisplatin in treating patients with oropharyngeal cancer.
    Actual start date of recruitment
    01 Oct 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 7 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 61
    Country: Number of subjects enrolled
    United States: 243
    Country: Number of subjects enrolled
    Saudi Arabia: 1
    Country: Number of subjects enrolled
    Ireland: 1
    Worldwide total number of subjects
    306
    EEA total number of subjects
    1
    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)
    215
    From 65 to 84 years
    91
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 From October 27th 2014 to February 7th 2017, a total of 316 patients were enrolled and 308 were randomized, of whom 2 were subsequently determined to ineligible

    Pre-assignment
    Screening details
    		 After first step registration and prior to randomization, patients were tested for p16. Only patients with p16-positive tumors continued on to randomization. In total, 316 patients were enrolled and 308 were randomized.

    Pre-assignment period milestones
    Number of subjects started
    		 308 [1]
    Number of subjects completed
    		 306

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Protocol deviation: 2
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 308 subjects were randomized but only 306 subjects were randomized and eligible.
    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IMRT 6 Weeks + Cisplatin
    Arm description
    		 Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    40 mg/m2 IV (intravenously) weekly for 6 weeks Radiation: IMRT 6 weeks, 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

    Arm title
    		 IMRT 5 weeks
    Arm description
    		 Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy
    Arm type
    		 Intenisty-modulated Radiotherapy

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Started
    157
    149
    Completed
    157
    149

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    IMRT 6 Weeks + Cisplatin
    Reporting group description
    		 Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

    Reporting group title
    IMRT 5 weeks
    Reporting group description
    		 Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy

    Reporting group values
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks Total
    Number of subjects
    		 157 149 306
    Age categorical
    Randomized and eligible patients
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 108 107 215
        From 65-84 years
    		 49 42 91
    Gender categorical
    Units: Subjects
        Female
    		 24 25 49
        Male
    		 133 124 257
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 3 7 10
        Not Hispanic or Latino
    		 143 130 273
        Unknown or Not Reported
    		 11 12 23
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 1 2
        Asian
    		 0 4 4
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 1 2 3
        White
    		 151 130 281
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 4 12 16
    Zubrod performance status
    Units: Subjects
        0: Asymptomatic
    		 132 113 245
        1: Symptomatic but completely ambulatory
    		 25 36 61
    Smoking history (pack years)
    Smoking history as measured in pack-years, calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked.
    Units: Subjects
        =0
    		 112 101 213
        >0-<5
    		 26 32 58
        5-10
    		 19 16 35
    T Stage
    Tumor stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.
    Units: Subjects
        T1
    		 64 51 115
        T2
    		 67 80 147
        T3
    		 26 18 44
    N Stage
    Regional lymph nodes staging per American Joint Committee on Cancer (AJCC) 7th ed. refers to the number and/or extent of spread of lymph nodes that contain cancer. The higher the number after the N, the greater the involvement of regional lymph nodes.
    Units: Subjects
        N0
    		 6 7 13
        N1
    		 28 34 62
        N2a
    		 24 19 43
        N2b
    		 99 89 188
    Primary tumor site
    Units: Subjects
        Oropharynx NOS
    		 4 13 17
        Tonsillar fossa
    		 83 78 161
        Base of tongue
    		 68 58 126
        Pharyngeal oropharynx
    		 1 0 1
        Posterior pharyngeal wll
    		 1 0 1
    Radiation Therapy (RT) planning (as stratified)
    Radiation therapy plan included unilateral or bilateral radiation to the neck, as provided by the treating site at stratification.
    Units: Subjects
        Unilateral
    		 52 47 99
        Bilateral
    		 105 102 207
    RT planning (per central review)
    Radiation therapy plan included unilateral or bilateral radiation to the neck, as provided by central review by the study radiation oncologist.
    Units: Subjects
        Unilateral
    		 16 21 37
        Bilateral
    		 136 125 261
        Unknown
    		 5 3 8

    End points

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    End points reporting groups
    Reporting group title
    IMRT 6 Weeks + Cisplatin
    Reporting group description
    		 Cisplatin: 40 mg/m2 IV (intravenously) weekly for 6 weeks IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

    Reporting group title
    IMRT 5 weeks
    Reporting group description
    		 Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy

    Subject analysis set title
    Both Arms Combined
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    IMRT 6 Weeks + Cisplatin (Arm 1)and IMRT 5 weeks (Arm 2) combined

    Subject analysis set title
    Both Arms Combined
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    IMRT 6 Weeks + Cisplatin (Arm 1)and IMRT 5 weeks (Arm 2) combined This subject set is created as a workaround for reporting statistical analysis.

    Subject analysis set title
    IMRT 6 Weeks + Cisplatin (Arm 1)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    This subject analysis set is being set up for a workaround for reporting statistical analysis

    Subject analysis set title
    IMRT 5 Weeks (Arm 2)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    This subject analysis set is set up as a workaround to report statistical analysis

    Subject analysis set title
    IMRT 6 Weeks + Cisplatin (Arm 1) 1 month post-RT
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subject analysis set Arm 1 - 1 month post RT

    Subject analysis set title
    IMRT 5 Weeks (Arm 2) 1 month post RT
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subject analysis set - Arm 2 1 month Post RT

    Subject analysis set title
    IMRT 6 Weeks + Cisplatin (Arm 1) 6 months post-RT
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    6 months after end of radiation therapy (RT)

    Subject analysis set title
    IMRT 5 weeks (Arm 2) 6 months post RT
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    6 months after end of radiation therapy (RT)

    Subject analysis set title
    IMRT 6 Weeks + Cisplatin (Arm 1) 1 year post-RT
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    1 year after end of Radiation therapy (RT)

    Subject analysis set title
    IMRT 5 weeks (Arm 2) 1 year post RT
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    1 year after end of radiation therapy (RT)

    Subject analysis set title
    IMRT 6 Weeks + Cisplatin (Arm 1) 2 years post-RT
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    2 years after end of radiation therapy (RT)

    Subject analysis set title
    IMRT 5 weeks (Arm 2) 2 years post RT
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    2 years after end of radiation therapy (RT)

    Primary: Percentage of Participants Alive Without Progression at Two Years (Progression-free Survival)

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    End point title
    		 Percentage of Participants Alive Without Progression at Two Years (Progression-free Survival)
    End point description
    Progression is defined as local, regional, or distant disease progression or death due to any cause. Percentage is estimated using the binomial distribution. Two-year data was available for 147/157 (Arm 1) and 145/149 (Arm 2) randomized and eligible participants. One-side confidence interval
    End point type
    Primary
    End point timeframe
    From randomization to 2 years
    End point values
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Number of subjects analysed
    147
    145
    Units: Percentage of Participants
        number (not applicable)
    90.5
    87.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Assuming a binomial distribution, 140 eligible patients per arm were required for 80% power and 1-sided type I error rate of 10% to test the null hypothesis of 2-year progression-free survival (PFS) rate ≤ 85% against the alternative hypothesis of > 85% with a binomial test. The arms are not compared to each other; they are each tested separately against the null hypothesis.
    Comparison groups
    IMRT 6 Weeks + Cisplatin v IMRT 5 weeks
    Number of subjects included in analysis
    292
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.04 [1]
    Method
    		 Binomial
    Confidence interval
    Notes
    [1] - One-sided significance level=0.10
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Assuming a binomial distribution, 140 eligible patients per arm were required for 80% power and 1-sided type I error rate of 10% to test the null hypothesis of 2-year PFS rate ≤ 85% against the alternative hypothesis of > 85% with a binomial test. The arms are not compared to each other; they are each tested separately against the null hypothesis.
    Comparison groups
    IMRT 5 weeks v IMRT 6 Weeks + Cisplatin
    Number of subjects included in analysis
    292
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.23
    Method
    		 Binomial
    Confidence interval
         level
    		 10%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -

    Secondary: Percentage of Participants With Local-regional Failure

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    End point title
    		 Percentage of Participants With Local-regional Failure
    End point description
    Local-regional failure is defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression. Distant metastasis and death due to other causes are considered competing risks. Local-regional failure time is defined as time from randomization to the date of first progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.
    End point type
    Secondary
    End point timeframe
    From randomization to 2 years
    End point values
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Number of subjects analysed
    157
    149
    Units: percentage of participants
    number (confidence interval 95%)
        Six months
    0.7 (0.1 to 3.3)
    2.0 (0.6 to 5.4)
        Two Years
    3.3 (1.2 to 7.1)
    9.5 (5.5 to 15.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    IMRT 5 weeks v IMRT 6 Weeks + Cisplatin
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.02 [2]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.17
         upper limit
    		 0.9
    Notes
    [2] - Two-sided significance level = 0.05

    Secondary: Percentage of Participants With Distant Metastasis

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    End point title
    		 Percentage of Participants With Distant Metastasis
    End point description
    Distant metastasis is defined as distant progression. Local-regional failure and death due to any cause are considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.
    End point type
    Secondary
    End point timeframe
    From randomization to 2 years
    End point values
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Number of subjects analysed
    157
    149
    Units: Percentage of participants
    number (confidence interval 95%)
        Six months
    0 (0 to 0)
    0 (0 to 0)
        Two years
    4 (1.6 to 8.0)
    2.1 (0.6 to 5.5)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    IMRT 6 Weeks + Cisplatin v IMRT 5 weeks
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.58 [4]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 5.08
    Notes
    [3] - Estimation Comments Reference level = IMRT 5 weeks
    [4] - Two-sided significance level = 0.05

    Secondary: Percentage of Participants Alive

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    End point title
    		 Percentage of Participants Alive
    End point description
    Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.
    End point type
    Secondary
    End point timeframe
    From randomization to 2 years
    End point values
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Number of subjects analysed
    157
    149
    Units: Percentage of participants
    number (confidence interval 95%)
        Six months
    99.3 (98.1 to 100)
    98.0 (95.7 to 100)
        Two years
    96.7 (93.9 to 99.5)
    97.3 (94.6 to 99.9)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    IMRT 6 Weeks + Cisplatin v IMRT 5 weeks
    Number of subjects included in analysis
    306
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.93 [6]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.31
         upper limit
    		 2.95
    Notes
    [5] - Estimation Comments Reference level = IMRT 5 weeks
    [6] - Two-side significance level = 0.05

    Secondary: Percentage of Participants With Grade 3+ Adverse Events (End of RT)

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    End point title
    		 Percentage of Participants With Grade 3+ Adverse Events (End of RT)
    End point description
    Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
    End point type
    Secondary
    End point timeframe
    End of radiation therapy (RT) (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2).
    End point values
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Number of subjects analysed
    152
    147
    Units: Percentage of Participants
        number (confidence interval 95%)
    73.7 (65.9 to 80.5)
    46.3 (38.0 to 54.7)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    End of RT
    Comparison groups
    IMRT 6 Weeks + Cisplatin v IMRT 5 weeks
    Number of subjects included in analysis
    299
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 < 0.0001 [8]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [7] - End of RT
    [8] - Two-sided significance level = 0.05

    Secondary: Mean One-year Total MD Anderson Dysphagia Inventory (MDADI) Score (Patient-reported Swallowing Outcome)

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    End point title
    		 Mean One-year Total MD Anderson Dysphagia Inventory (MDADI) Score (Patient-reported Swallowing Outcome)
    End point description
    The MDADI is a 20-item tool with each item scored as Strongly agree; Agree; No opinion; Disagree; or Strongly disagree. There is 1 global item (G1), 6 emotional subscale items (E2-E7), 5 functional subscale items (F1-F5), and 8 physical subscale items (P1-P8). For all items except E7 and F2, Strongly agree corresponds to a score of 1, Agree 2, No opinion 3, Disagree 4, and Strongly disagree 5. For E7 and F2, the scores are reversed; these 2 items are rescored to match the others before calculating summary scores. The composite (total) score is the mean of the 19 items (other than G1) X 20. Composite scores range from 20 to 100 with higher scores indicating less dysphagia.
    End point type
    Secondary
    End point timeframe
    One year post-RT. Radiation therapy (RT) ends at approximately 6 weeks for Arm 1 and 5 weeks for Arm 2
    End point values
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Number of subjects analysed
    121 [9]
    106 [10]
    Units: Score on scale
        arithmetic mean (confidence interval 95%)
    85.3 (82.5 to 88.1)
    81.8 (79.0 to 84.5)
    Notes
    [9] - 121 Arm 1 participants had one year post-RT data.
    [10] - 106 Arm 2 participants had one year post-RT data
    No statistical analyses for this end point

    Secondary: Negative Predictive Value (NPV) of Post-treatment FDG-PET/CT Scan [Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT)] for Progression-free Survival and Local-regional Control at Two Years

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    End point title
    		 Negative Predictive Value (NPV) of Post-treatment FDG-PET/CT Scan [Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT)] for Progression-free Survival and Local-regional Control at Two Years
    End point description
    NPV is the percentage of participants alive and failure-free at 2 years among those with a negative post-treatment scan, as evaluated by central review. Negative scan determined as follows: primary site, right neck, left neck evaluated using a 5-point ordinal scale: 1-Definite complete metabolic response (CMR), 2-Likely CMR, 3-Likely inflammatory, 4-Likely residual metabolic disease (RMD), and 5-Definite RMD. 'Negative'= 1 or 2, 'Indeterminate'=3, 'Positive' = 4 or 5. 'Negative' for all three evaluation sites = overall score of 'Negative.' Progression (failure) is defined as local, regional, or distant disease progression (PR) or any death. Local-regional progression (failure) is defined as local or regional PR, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks post RT, death due to study cancer or unknown causes without documented PR. The protocol specified that both arms would be combined for analysis.
    End point type
    Secondary
    End point timeframe
    3 months (scan) and two years after the end of RT (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2)
    End point values
    		 Both Arms Combined
    Number of subjects analysed
    115
    Units: Percentage of participants
    number (not applicable)
        Progression-free Survival
    92.0
        Local-regional failure
    94.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Grade 3+ Adverse Events (1 month Post RT)

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    End point title
    		 Percentage of Participants With Grade 3+ Adverse Events (1 month Post RT)
    End point description
    Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
    End point type
    Secondary
    End point timeframe
    1 month post radiation therapy (RT)
    End point values
    		 IMRT 6 Weeks + Cisplatin (Arm 1) 1 month post-RT IMRT 5 Weeks (Arm 2) 1 month post RT
    Number of subjects analysed
    144
    142
    Units: Percentage of Participants
        number (confidence interval 95%)
    36.1 (28.3 to 44.5)
    28.2 (21.0 to 36.3)
    Statistical analysis title
    		 One month after end of RT
    Comparison groups
    IMRT 6 Weeks + Cisplatin (Arm 1) 1 month post-RT v IMRT 5 Weeks (Arm 2) 1 month post RT
    Number of subjects included in analysis
    286
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.17 [11]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [11] - Two-sided significance level = 0.05

    Secondary: Percentage of Participants With Grade 3+ Adverse Events (6 months Post RT)

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    End point title
    		 Percentage of Participants With Grade 3+ Adverse Events (6 months Post RT)
    End point description
    Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
    End point type
    Secondary
    End point timeframe
    6 months post Radiation therapy (RT)
    End point values
    		 IMRT 6 Weeks + Cisplatin (Arm 1) 6 months post-RT IMRT 5 weeks (Arm 2) 6 months post RT
    Number of subjects analysed
    140
    126
    Units: Percentage of participants
        number (confidence interval 95%)
    17.9 (11.9 to 25.2)
    11.1 (6.2 to 17.9)
    Statistical analysis title
    		 6 months after end of RT
    Comparison groups
    IMRT 6 Weeks + Cisplatin (Arm 1) 6 months post-RT v IMRT 5 weeks (Arm 2) 6 months post RT
    Number of subjects included in analysis
    266
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    P-value
    		 = 0.16
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [12] - Two-side significance level = 0.05

    Secondary: Percentage of Participants With Grade 3+ Adverse Events (1 year Post RT)

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    End point title
    		 Percentage of Participants With Grade 3+ Adverse Events (1 year Post RT)
    End point description
    Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
    End point type
    Secondary
    End point timeframe
    1 year after end of radiation therapy (RT)
    End point values
    		 IMRT 6 Weeks + Cisplatin (Arm 1) 1 year post-RT IMRT 5 weeks (Arm 2) 1 year post RT
    Number of subjects analysed
    143
    134
    Units: Percentage of Participants
        number (confidence interval 95%)
    14.0 (8.8 to 20.8)
    9.0 (4.7 to 15.1)
    Statistical analysis title
    		 1 year after end of RT
    Comparison groups
    IMRT 6 Weeks + Cisplatin (Arm 1) 1 year post-RT v IMRT 5 weeks (Arm 2) 1 year post RT
    Number of subjects included in analysis
    277
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.26
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [13] - Two-sided significance level =0.05

    Secondary: Percentage of Participants With Grade 3+ Adverse Events (2 years Post RT)

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    End point title
    		 Percentage of Participants With Grade 3+ Adverse Events (2 years Post RT)
    End point description
    Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
    End point type
    Secondary
    End point timeframe
    2 years after end of radiation therapy (RT)
    End point values
    		 IMRT 6 Weeks + Cisplatin (Arm 1) 2 years post-RT IMRT 5 weeks (Arm 2) 2 years post RT
    Number of subjects analysed
    128
    122
    Units: Percentage of participants
        number (confidence interval 95%)
    8.6 (4.4 to 14.9)
    7.4 (3.4 to 13.5)
    Statistical analysis title
    		 2 years after end of RT
    Comparison groups
    IMRT 6 Weeks + Cisplatin (Arm 1) 2 years post-RT v IMRT 5 weeks (Arm 2) 2 years post RT
    Number of subjects included in analysis
    250
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [14]
    P-value
    		 = 0.82
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [14] - Two-side significance level = 0.05

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Weekly during treatment, 1 & 3 months after EOT, then every 3 months from end of treatment for 2 years, every 6 months from end of treatment for 3 years, then annually until study completion. Maximum follow-up at time of reporting was 4.1 years.
    Adverse event reporting additional description
    The Assessment type for the Adverse Events documented was both Systematic and Non-Systematic.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    IMRT 6 Weeks + Cisplatin
    Reporting group description
    		 IMRT 6 weeks: Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy

    Reporting group title
    IMRT 5 weeks
    Reporting group description
    		 Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy

    Serious adverse events
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 152 (20.39%)
    11 / 147 (7.48%)
         number of deaths (all causes)
    6
    6
         number of deaths resulting from adverse events
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thromboemboloic event
    alternative assessment type: Non-systematic
         subjects affected / exposed
    6 / 152 (3.95%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    3 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fever
    alternative assessment type: Non-systematic
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flu like symptoms
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 152 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pharyngeal mucositis
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration
    alternative assessment type: Non-systematic
         subjects affected / exposed
    3 / 152 (1.97%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngolaryngeal pain
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sore throat
    alternative assessment type: Non-systematic
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusion
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Lymphocyte count decreased
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    3 / 152 (1.97%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Creatinine increased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Heart failure
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Dysarthria
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysgeusia
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 152 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    4 / 152 (2.63%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 152 (0.66%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dry mouth
         subjects affected / exposed
    1 / 152 (0.66%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    4 / 152 (2.63%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Esophagitis
    alternative assessment type: Non-systematic
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal pain
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral pain
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Neck soft tissue necrosis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis infectious
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal infection
    alternative assessment type: Non-systematic
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    4 / 152 (2.63%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
    alternative assessment type: Non-systematic
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 IMRT 6 Weeks + Cisplatin IMRT 5 weeks
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    152 / 152 (100.00%)
    147 / 147 (100.00%)
    Vascular disorders
    Hypertension
    alternative assessment type: Non-systematic
         subjects affected / exposed
    10 / 152 (6.58%)
    11 / 147 (7.48%)
         occurrences all number
    25
    21
    Lymphoedema
    alternative assessment type: Non-systematic
         subjects affected / exposed
    11 / 152 (7.24%)
    11 / 147 (7.48%)
         occurrences all number
    13
    13
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    138 / 152 (90.79%)
    117 / 147 (79.59%)
         occurrences all number
    280
    245
    Fever
    alternative assessment type: Non-systematic
         subjects affected / exposed
    9 / 152 (5.92%)
    2 / 147 (1.36%)
         occurrences all number
    9
    2
    Neck edema
    alternative assessment type: Non-systematic
         subjects affected / exposed
    4 / 152 (2.63%)
    10 / 147 (6.80%)
         occurrences all number
    6
    12
    Pain
         subjects affected / exposed
    115 / 152 (75.66%)
    121 / 147 (82.31%)
         occurrences all number
    226
    262
    General disorders and administration site conditions - Other
         subjects affected / exposed
    6 / 152 (3.95%)
    11 / 147 (7.48%)
         occurrences all number
    13
    14
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    38 / 152 (25.00%)
    37 / 147 (25.17%)
         occurrences all number
    62
    57
    Hiccups
    alternative assessment type: Non-systematic
         subjects affected / exposed
    11 / 152 (7.24%)
    0 / 147 (0.00%)
         occurrences all number
    11
    0
    Hoarseness
    alternative assessment type: Non-systematic
         subjects affected / exposed
    18 / 152 (11.84%)
    19 / 147 (12.93%)
         occurrences all number
    25
    25
    Respiratory, thoracic and mediastinal disorders - Other
    alternative assessment type: Non-systematic
         subjects affected / exposed
    8 / 152 (5.26%)
    8 / 147 (5.44%)
         occurrences all number
    9
    9
    Sore throat
    alternative assessment type: Non-systematic
         subjects affected / exposed
    42 / 152 (27.63%)
    28 / 147 (19.05%)
         occurrences all number
    55
    39
    Voice alteration
    alternative assessment type: Non-systematic
         subjects affected / exposed
    11 / 152 (7.24%)
    13 / 147 (8.84%)
         occurrences all number
    11
    14
    Pharyngeal mucosistis
         subjects affected / exposed
    29 / 152 (19.08%)
    44 / 147 (29.93%)
         occurrences all number
    39
    61
    Psychiatric disorders
    Anxiety
    alternative assessment type: Non-systematic
         subjects affected / exposed
    11 / 152 (7.24%)
    15 / 147 (10.20%)
         occurrences all number
    12
    18
    Depression
    alternative assessment type: Non-systematic
         subjects affected / exposed
    12 / 152 (7.89%)
    7 / 147 (4.76%)
         occurrences all number
    20
    9
    Insomnia
         subjects affected / exposed
    44 / 152 (28.95%)
    34 / 147 (23.13%)
         occurrences all number
    62
    55
    Investigations
    Alanine aminotransferase increased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    14 / 152 (9.21%)
    7 / 147 (4.76%)
         occurrences all number
    15
    8
    Aspartate aminotransferase increased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    12 / 152 (7.89%)
    7 / 147 (4.76%)
         occurrences all number
    12
    9
    Blood bilirubin increased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    9 / 152 (5.92%)
    5 / 147 (3.40%)
         occurrences all number
    13
    7
    Creatinine increased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    26 / 152 (17.11%)
    3 / 147 (2.04%)
         occurrences all number
    28
    3
    Lymphocyte count decreased
         subjects affected / exposed
    118 / 152 (77.63%)
    87 / 147 (59.18%)
         occurrences all number
    248
    158
    Neutrophil count decreased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    33 / 152 (21.71%)
    3 / 147 (2.04%)
         occurrences all number
    40
    3
    Platelet count decreased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    53 / 152 (34.87%)
    8 / 147 (5.44%)
         occurrences all number
    70
    12
    Weight loss
         subjects affected / exposed
    119 / 152 (78.29%)
    101 / 147 (68.71%)
         occurrences all number
    235
    186
    White blood cell count decreased
    alternative assessment type: Non-systematic
         subjects affected / exposed
    56 / 152 (36.84%)
    13 / 147 (8.84%)
         occurrences all number
    90
    14
    Injury, poisoning and procedural complications
    Dermatitis radiation
         subjects affected / exposed
    113 / 152 (74.34%)
    109 / 147 (74.15%)
         occurrences all number
    147
    135
    Nervous system disorders
    Dizziness
    alternative assessment type: Non-systematic
         subjects affected / exposed
    15 / 152 (9.87%)
    8 / 147 (5.44%)
         occurrences all number
    17
    8
    Dysgeusia
         subjects affected / exposed
    142 / 152 (93.42%)
    132 / 147 (89.80%)
         occurrences all number
    312
    281
    Headache
    alternative assessment type: Non-systematic
         subjects affected / exposed
    12 / 152 (7.89%)
    11 / 147 (7.48%)
         occurrences all number
    13
    14
    Peripheral sensory neuropathy
         subjects affected / exposed
    29 / 152 (19.08%)
    15 / 147 (10.20%)
         occurrences all number
    51
    29
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    92 / 152 (60.53%)
    35 / 147 (23.81%)
         occurrences all number
    172
    49
    Ear and labyrinth disorders
    Ear pain
    alternative assessment type: Non-systematic
         subjects affected / exposed
    8 / 152 (5.26%)
    4 / 147 (2.72%)
         occurrences all number
    10
    4
    Hearing impaired
         subjects affected / exposed
    43 / 152 (28.29%)
    34 / 147 (23.13%)
         occurrences all number
    95
    72
    Tinnitus
         subjects affected / exposed
    65 / 152 (42.76%)
    41 / 147 (27.89%)
         occurrences all number
    119
    75
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    92 / 152 (60.53%)
    53 / 147 (36.05%)
         occurrences all number
    118
    75
    Diarrhoea
         subjects affected / exposed
    26 / 152 (17.11%)
    14 / 147 (9.52%)
         occurrences all number
    30
    17
    Dry mouth
         subjects affected / exposed
    150 / 152 (98.68%)
    142 / 147 (96.60%)
         occurrences all number
    391
    365
    Dyspepsia
         subjects affected / exposed
    42 / 152 (27.63%)
    31 / 147 (21.09%)
         occurrences all number
    57
    52
    Dysphagia
         subjects affected / exposed
    124 / 152 (81.58%)
    119 / 147 (80.95%)
         occurrences all number
    259
    282
    Gastrooesophageal reflux disease
    alternative assessment type: Non-systematic
         subjects affected / exposed
    8 / 152 (5.26%)
    3 / 147 (2.04%)
         occurrences all number
    9
    6
    Gastrointestinal disorder
    alternative assessment type: Non-systematic
         subjects affected / exposed
    16 / 152 (10.53%)
    13 / 147 (8.84%)
         occurrences all number
    29
    19
    Mucositis oral
         subjects affected / exposed
    131 / 152 (86.18%)
    121 / 147 (82.31%)
         occurrences all number
    193
    172
    Nausea
         subjects affected / exposed
    109 / 152 (71.71%)
    62 / 147 (42.18%)
         occurrences all number
    145
    84
    Oral pain
    alternative assessment type: Non-systematic
         subjects affected / exposed
    9 / 152 (5.92%)
    9 / 147 (6.12%)
         occurrences all number
    11
    13
    Vomiting
         subjects affected / exposed
    51 / 152 (33.55%)
    30 / 147 (20.41%)
         occurrences all number
    61
    37
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    28 / 152 (18.42%)
    25 / 147 (17.01%)
         occurrences all number
    34
    34
    Dry skin
         subjects affected / exposed
    36 / 152 (23.68%)
    35 / 147 (23.81%)
         occurrences all number
    54
    45
    Skin and subcutaneous tissue disorders - Other
    alternative assessment type: Non-systematic
         subjects affected / exposed
    12 / 152 (7.89%)
    10 / 147 (6.80%)
         occurrences all number
    15
    13
    Skin hyperpigmentation
    alternative assessment type: Non-systematic
         subjects affected / exposed
    3 / 152 (1.97%)
    9 / 147 (6.12%)
         occurrences all number
    3
    9
    Endocrine disorders
    Hypothyroidism
    alternative assessment type: Non-systematic
         subjects affected / exposed
    18 / 152 (11.84%)
    16 / 147 (10.88%)
         occurrences all number
    28
    23
    Musculoskeletal and connective tissue disorders
    Neck pain
    alternative assessment type: Non-systematic
         subjects affected / exposed
    7 / 152 (4.61%)
    11 / 147 (7.48%)
         occurrences all number
    7
    15
    Trismus
         subjects affected / exposed
    22 / 152 (14.47%)
    25 / 147 (17.01%)
         occurrences all number
    31
    36
    Infections and infestations
    Infections and infestations - Other
    alternative assessment type: Non-systematic
         subjects affected / exposed
    12 / 152 (7.89%)
    7 / 147 (4.76%)
         occurrences all number
    12
    9
    Mucosal infection
    alternative assessment type: Non-systematic
         subjects affected / exposed
    10 / 152 (6.58%)
    10 / 147 (6.80%)
         occurrences all number
    11
    14
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    81 / 152 (53.29%)
    69 / 147 (46.94%)
         occurrences all number
    116
    96
    Dehydration
    alternative assessment type: Non-systematic
         subjects affected / exposed
    23 / 152 (15.13%)
    11 / 147 (7.48%)
         occurrences all number
    28
    12
    Hyperglycaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    27 / 152 (17.76%)
    13 / 147 (8.84%)
         occurrences all number
    35
    16
    Hyperkalaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    9 / 152 (5.92%)
    4 / 147 (2.72%)
         occurrences all number
    11
    5
    Hypoalbuminaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    23 / 152 (15.13%)
    11 / 147 (7.48%)
         occurrences all number
    26
    11
    Hypocalcaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    14 / 152 (9.21%)
    4 / 147 (2.72%)
         occurrences all number
    14
    4
    Hypokalaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    16 / 152 (10.53%)
    4 / 147 (2.72%)
         occurrences all number
    22
    8
    Hypomagnesaemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    31 / 152 (20.39%)
    3 / 147 (2.04%)
         occurrences all number
    40
    3
    Hyponatraemia
    alternative assessment type: Non-systematic
         subjects affected / exposed
    33 / 152 (21.71%)
    9 / 147 (6.12%)
         occurrences all number
    44
    11

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Sep 2016
    SA01 Protocol Amendment 2 24-May-2016 which included the addition of an optional modified barium swallow sub study and changes to the open eligibility checklist.
    12 Feb 2018
    Protocol Amendment 3 20-Dec-2017 was submitted as a non-substantial amendment.

    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/33507809
    For support, Contact us.
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