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    Clinical Trial Results:
    A phase Ib, open-label, multicenter, dose escalation and expansion study, to evaluate the safety, pharmacokinetics and activity of INC280 in combination with cetuximab in c-MET positive CRC and HNSCC patients who have progressed after anti-EGFR monoclonal antibody therapy

    Summary
    EudraCT number
    		 2014-000579-20
    Trial protocol
    		 ES   IT   DE   BE  
    Global end of trial date
    20 Jan 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Jan 2018
    First version publication date
    27 Jan 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CINC280X2104
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02205398
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    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
    20 Jan 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Jan 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Jan 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To estimate the maximum tolerated dose (MTD) and/or recommended dose of INC280 in combination with cetuximab in c-MET positive mCRC and HNSCC patients.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Jul 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 1
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    Germany: 1
    Worldwide total number of subjects
    13
    EEA total number of subjects
    8
    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)
    9
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Overall, 13 patients were enrolled in the study between first patient first visit (FPFV, 28-Jul-2014) and last patient last visit (LPLV, 20-Jan-2017). All 13 patients discontinued treatment, among these, 12 patients discontinued due to progressive disease and one patient had AEs leading to study treatment discontinuation.

    Pre-assignment
    Screening details
    		 The patient population of the study consists of adult patients with K/NRAS WT and c-MET positive mCRC and c-MET positive recurrent/metastatic HNSCC who have received at least one previous line of treatment for the metastatic disease. The last treatment should include an anti-EGFR antibody (cetuximab/panitumumab or only cetuximab for HNSCC).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 INC280 150 mg BID + Cetuximab
    Arm description
    		 The starting dose for INC280 was 150 mg bid, administered continuously in combination with a fixed dose of cetuximab of 400 mg/m2 as the initial dose (C1D1) and 250 mg/m2 as subsequent weekly doses in 28-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    INC280 and cetuximab
    Investigational medicinal product code
    Other name
    BID
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The starting dose for INC280 was 150 mg bid, administered continuously twice a day (bid) dosing regimen and in combination with a fixed dose of intravenous infusion of cetuximab (400 mg/m2 initial infusion and 250 mg/m2 on subsequent infusions) every week (qwk) in 28-day cycles.

    Arm title
    		 INC280 300 mg BID + Cetuximab
    Arm description
    		 The starting dose for INC280 was 150 mg bid, administered continuously in combination with a fixed dose of cetuximab of 400 mg/m2 as the initial dose (C1D1) and 250 mg/m2 as subsequent weekly doses in 28-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    INC280 and cetuximab
    Investigational medicinal product code
    Other name
    BID
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The starting dose for INC280 was 300 mg bid, administered continuously twice a day (bid) dosing regimen and in combination with a fixed dose of intravenous infusion of cetuximab (400 mg/m2 initial infusion and 250 mg/m2 on subsequent infusions) every week (qwk) in 28-day cycles.

    Arm title
    		 INC280 400 mg BID + Cetuximab
    Arm description
    		 The starting dose for INC280 was 150 mg bid, administered continuously in combination with a fixed dose of cetuximab of 400 mg/m2 as the initial dose (C1D1) and 250 mg/m2 as subsequent weekly doses in 28-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    INC280 and cetuximab
    Investigational medicinal product code
    Other name
    BID
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The starting dose for INC280 was 400 mg bid, administered continuously twice a day (bid) dosing regimen and in combination with a fixed dose of intravenous infusion of cetuximab (400 mg/m2 initial infusion and 250 mg/m2 on subsequent infusions) every week (qwk) in 28-day cycles.

    Number of subjects in period 1
    		INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab
    Started
    4
    3
    6
    Completed
    0
    0
    0
    Not completed
    4
    3
    6
         INC280 150 mg BID + Cetuximab
    4
    3
    -
         Adverse event, non-fatal
    -
    -
    1
         Progressive disease
    -
    -
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 -

    Reporting group values
    		 Overall Study Total
    Number of subjects
    		 13 13
    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)
    		 9 9
        From 65-84 years
    		 4 4
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.9 ( 12.97 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2 2
        Male
    		 11 11
    Subject analysis sets

    Subject analysis set title
    INC280 150 mg BID + Cetuximab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set (FAS) comprised of all patients who received at least one full or partial dose of INC280 or cetuximab. The FAS was used for all listings of raw data. Unless otherwise specified the FAS was the default analysis set used for all analyses.

    Subject analysis set title
    INC280 300 mg BID + Cetuximab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set (FAS) comprised of all patients who received at least one full or partial dose of INC280 or cetuximab. The FAS was used for all listings of raw data. Unless otherwise specified the FAS was the default analysis set used for all analyses.

    Subject analysis set title
    INC280 400 mg BID + Cetuximab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set (FAS) comprised of all patients who received at least one full or partial dose of INC280 or cetuximab. The FAS was used for all listings of raw data. Unless otherwise specified the FAS was the default analysis set used for all analyses.

    Subject analysis sets values
    		 INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab
    Number of subjects
    4
    3
    6
    Age categorical
    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)
    3
    2
    4
        From 65-84 years
    1
    1
    2
        85 years and over
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    54.3 ( 18.32 )
    64.0 ( 40.74 )
    61.8 ( 7.25 )
    Gender categorical
    Units: Subjects
        Female
    1
    1
    0
        Male
    3
    2
    6

    End points

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    End points reporting groups
    Reporting group title
    INC280 150 mg BID + Cetuximab
    Reporting group description
    		 The starting dose for INC280 was 150 mg bid, administered continuously in combination with a fixed dose of cetuximab of 400 mg/m2 as the initial dose (C1D1) and 250 mg/m2 as subsequent weekly doses in 28-day cycles.

    Reporting group title
    INC280 300 mg BID + Cetuximab
    Reporting group description
    		 The starting dose for INC280 was 150 mg bid, administered continuously in combination with a fixed dose of cetuximab of 400 mg/m2 as the initial dose (C1D1) and 250 mg/m2 as subsequent weekly doses in 28-day cycles.

    Reporting group title
    INC280 400 mg BID + Cetuximab
    Reporting group description
    		 The starting dose for INC280 was 150 mg bid, administered continuously in combination with a fixed dose of cetuximab of 400 mg/m2 as the initial dose (C1D1) and 250 mg/m2 as subsequent weekly doses in 28-day cycles.

    Subject analysis set title
    INC280 150 mg BID + Cetuximab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set (FAS) comprised of all patients who received at least one full or partial dose of INC280 or cetuximab. The FAS was used for all listings of raw data. Unless otherwise specified the FAS was the default analysis set used for all analyses.

    Subject analysis set title
    INC280 300 mg BID + Cetuximab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set (FAS) comprised of all patients who received at least one full or partial dose of INC280 or cetuximab. The FAS was used for all listings of raw data. Unless otherwise specified the FAS was the default analysis set used for all analyses.

    Subject analysis set title
    INC280 400 mg BID + Cetuximab
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The full analysis set (FAS) comprised of all patients who received at least one full or partial dose of INC280 or cetuximab. The FAS was used for all listings of raw data. Unless otherwise specified the FAS was the default analysis set used for all analyses.

    Primary: Maximum tolerated dose (MTD) and/or recommended dose of INC280 in combination with cetuximab in c-MET positive mCRC and HNSCC patients

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    End point title
    		 Maximum tolerated dose (MTD) and/or recommended dose of INC280 in combination with cetuximab in c-MET positive mCRC and HNSCC patients [1]
    End point description
    MTD and/or RP2D of INC280 in combination with cetuximab, by evaluating number of patients who experienced toxicity that fulfills the criteria for a DLT). This analysis was done in the Dose Determining set (DDS). DDS consisted of all patients in the dose escalation part from the Safety Set who meet the minimum exposure to study treatment criterion and had sufficient safety evaluations during Cycle 1, or discontinued earlier due to DLT during Cycle 1.
    End point type
    Primary
    End point timeframe
    28 days
    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: No comparative statistical analysis was conducted for this endpoint. The relationship between dose and the probability of DLT was modelled using adaptive Bayesian logistic regression model with overdose control principle.
    End point values
    		 INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab
    Number of subjects analysed
    4
    3
    6
    Units: Number of participants
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Preliminary anti-tumor activity of the INC280 and cetuximab combination

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    End point title
    		 Preliminary anti-tumor activity of the INC280 and cetuximab combination
    End point description
    ORR is the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). This analysis was done in the full analysis set (FAS). FAS comprised of all patients who received at least one full or partial dose of INC280 or cetuximab. The FAS was used for all listings of raw data. Unless otherwise specified the FAS was the default analysis set used for all analyses.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab
    Number of subjects analysed
    4
    3
    6
    Units: Number of participants
        Complete response
    0
    0
    0
        Partial response
    0
    0
    0
        Stable disease
    1
    1
    4
        Progressive disease
    2
    1
    2
        Unknown
    1
    1
    0
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    To assess additional clinical activity of the INC280 and cetuximab combination as measured by Overall Survival for patients in the expansion part of the study. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab. The trial was terminated due to difficulties in identifying patients who met the eligibility criteria. As such the expansion arm was not opened and overall survival was not analyzed.
    End point type
    Secondary
    End point timeframe
    Every 12 weeks until the end of the trial
    End point values
    		 INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    Units: Number of participants
    Notes
    [2] - As a result of early termination, overall survival was not analyzed.
    [3] - As a result of early termination, overall survival was not analyzed.
    [4] - As a result of early termination, overall survival was not analyzed.
    No statistical analyses for this end point

    Secondary: Time versus plasma concentration profiles and basic PK parameters of INC280

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    End point title
    		 Time versus plasma concentration profiles and basic PK parameters of INC280
    End point description
    To characterize the PK profile of INC280 with cetuximab combination as measured by time versus plasma concentration profiles and basic PK parameters of INC280. A treatment cycle was defined as 28 days with no scheduled break between cycles. The trial was terminated because of difficulties in identifying patients who met the eligibility criteria.
    End point type
    Secondary
    End point timeframe
    During the first 4 Cycles of treatment or up to 16 weeks from the time of study treatment start
    End point values
    		 INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab
    Number of subjects analysed
    0 [5]
    0 [6]
    0 [7]
    Units: Number of participants
    Notes
    [5] - As a result of early termination, basic pharmacokinetic parameters were not analyzed.
    [6] - As a result of early termination, basic pharmacokinetic parameters were not analyzed.
    [7] - As a result of early termination, basic pharmacokinetic parameters were not analyzed.
    No statistical analyses for this end point

    Secondary: Progression Free Survival of INC280 and cetuximab combination – expansion part

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    End point title
    		 Progression Free Survival of INC280 and cetuximab combination – expansion part
    End point description
    To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Progression Free Survival in patients treated with the combination of INC280 and cetuximab.The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab. The trial was terminated because of difficulties in identifying patients who met the eligibility criteria.
    End point type
    Secondary
    End point timeframe
    Every 8 weeks from C1D1 until the end of study for up to 3 years
    End point values
    		 INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab
    Number of subjects analysed
    0 [8]
    0 [9]
    0 [10]
    Units: Number of participants
    Notes
    [8] - As a result of early termination, progression free survival was not analyzed.
    [9] - As a result of early termination, progression free survival was not analyzed.
    [10] - As a result of early termination, progression free survival was not analyzed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the date of first administration of any study drug to 30 days after date of last actual administration of any study drug (including start and stop date).
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    INC280 150 mg BID + Cetuximab
    Reporting group description
    		 INC280 150 mg BID + Cetuximab

    Reporting group title
    INC280 300 mg BID + Cetuximab
    Reporting group description
    		 INC280 300 mg BID + Cetuximab

    Reporting group title
    INC280 400 mg BID + Cetuximab
    Reporting group description
    		 INC280 400 mg BID + Cetuximab

    Reporting group title
    All patients
    Reporting group description
    		 All patients

    Serious adverse events
    		 INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab All patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    5 / 13 (38.46%)
         number of deaths (all causes)
    0
    1
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Stomatitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Device related infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 INC280 150 mg BID + Cetuximab INC280 300 mg BID + Cetuximab INC280 400 mg BID + Cetuximab All patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    6 / 6 (100.00%)
    13 / 13 (100.00%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Hypotension
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    3
    0
    0
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Chills
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Face oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    4 / 6 (66.67%)
    7 / 13 (53.85%)
         occurrences all number
    2
    2
    4
    8
    Impaired healing
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    6 / 13 (46.15%)
         occurrences all number
    2
    1
    3
    6
    Pyrexia
         subjects affected / exposed
    4 / 4 (100.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    7 / 13 (53.85%)
         occurrences all number
    5
    2
    2
    9
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    0
    1
    1
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
         occurrences all number
    1
    1
    1
    3
    Dyspnoea
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Dyspnoea exertional
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Nasal congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Productive cough
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Pulmonary embolism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Respiratory failure
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Depression
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 4 (100.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    5 / 13 (38.46%)
         occurrences all number
    5
    0
    3
    8
    Amylase increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    3 / 13 (23.08%)
         occurrences all number
    1
    0
    4
    5
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 4 (75.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    4 / 13 (30.77%)
         occurrences all number
    4
    0
    2
    6
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    2 / 13 (15.38%)
         occurrences all number
    0
    0
    2
    2
    Blood bilirubin increased
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
         occurrences all number
    2
    1
    1
    4
    C-reactive protein increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Lipase increased
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    4 / 13 (30.77%)
         occurrences all number
    2
    0
    2
    4
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    4
    4
    Platelet count decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    2
    2
    Weight decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Weight increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Injury, poisoning and procedural complications
    Corneal abrasion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Gastrointestinal stoma complication
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Incisional hernia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Infusion related reaction
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Nervous system disorders
    Depressed level of consciousness
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
         occurrences all number
    3
    0
    1
    4
    Leukocytosis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    2
    2
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    3 / 13 (23.08%)
         occurrences all number
    0
    1
    4
    5
    Abdominal pain upper
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Constipation
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
         occurrences all number
    1
    2
    0
    3
    Diarrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    3 / 13 (23.08%)
         occurrences all number
    0
    0
    7
    7
    Dry mouth
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    0
    1
    1
    2
    Nausea
         subjects affected / exposed
    2 / 4 (50.00%)
    3 / 3 (100.00%)
    2 / 6 (33.33%)
    7 / 13 (53.85%)
         occurrences all number
    4
    3
    2
    9
    Rectal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Stomatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Vomiting
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
         occurrences all number
    4
    1
    1
    6
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
         occurrences all number
    1
    1
    1
    3
    Dermatitis acneiform
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    4 / 13 (30.77%)
         occurrences all number
    2
    2
    0
    4
    Dry skin
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    2
    2
    Erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Hyperkeratosis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Photosensitivity reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Pruritus
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    1
    0
    2
    3
    Rash
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    4 / 6 (66.67%)
    4 / 13 (30.77%)
         occurrences all number
    0
    0
    4
    4
    Rash maculo-papular
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Skin fissures
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Skin toxicity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Skin ulcer
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Pollakiuria
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Spinal pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    1
    0
    1
    2
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Folliculitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    2 / 13 (15.38%)
         occurrences all number
    0
    0
    2
    2
    Herpes zoster
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Mucosal infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Paronychia
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    1
    1
    0
    2
    Skin infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Wound infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    5 / 13 (38.46%)
         occurrences all number
    4
    1
    2
    7
    Dehydration
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    3
    0
    0
    3
    Hypermagnesaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    3 / 6 (50.00%)
    7 / 13 (53.85%)
         occurrences all number
    3
    2
    3
    8
    Hypocalcaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
         occurrences all number
    1
    0
    2
    3
    Hypokalaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Hypomagnesaemia
         subjects affected / exposed
    2 / 4 (50.00%)
    3 / 3 (100.00%)
    2 / 6 (33.33%)
    7 / 13 (53.85%)
         occurrences all number
    3
    3
    4
    10
    Hypophosphataemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jun 2014
    The main reason for the this amendment was to comply with Health Authority request to revise the eligibility criteria in the protocol and extend the duration of use of highly effective methods of contraception during dosing and for at least 4 weeks after permanently discontinuing study treatment (by females and males).
    22 Sep 2014
    The main purpose of this amendment was to update the definition of c-MET positivity based on the recent preliminary data from the ongoing clinical studies with INC280.
    16 Jul 2015
    The main purpose of this amendment was to update the eligibility criteria to align with the current treatment paradigm for metastatic CRC and HNSCC by including patients who have received more than one prior regimen containing an anti-EGFR antibody.
    29 Mar 2016
    The major reason for this amendment was to optimize the management of liver toxicities and be consistent across the different INC280 studies.

    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.
    Recruitment in the CINC280X2104 study was halted due to difficulties in identifying patients who met the eligibility criteria.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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