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    Clinical Trial Results:
    A Phase II, Open-label, Multicenter, Randomized Study to Assess the Efficacy and Safety of GSK1120212 Compared with Docetaxel in 2nd Line Subjects with Targeted Mutations (KRAS, NRAS, BRAF, MEK1) in Locally Advanced or Metastatic Nonsmall Cell Lung Cancer (NSCLC Stage IIIBwet-IV).

    Summary
    EudraCT number
    		 2011-000634-11
    Trial protocol
    		 GR   ES   NL   IT   HU  
    Global end of trial date
    24 Sep 2013

    Results information
    Results version number
    		 v2(current)
    This version publication date
    23 Mar 2016
    First version publication date
    10 Jul 2015
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Minor correction required.

    Trial information

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    Trial identification
    Sponsor protocol code
    MEK114653
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    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
    24 Sep 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Sep 2013
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To compare Progression-Free Survival (PFS) in KRAS mutated NSCLC subjects who are receiving GSK1120212 with those receiving docetaxel.
    Protection of trial subjects
    Per protocol, trial subjects received full supportive care during the study including transfusions of blood and blood products, and treatment with antibiotics, anti-emetics, anti-diarrheals, and analgesics, and other care as deemed appropriate, and in accordance with their institutional guidelines.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Sep 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 21
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    France: 28
    Country: Number of subjects enrolled
    Greece: 3
    Country: Number of subjects enrolled
    Hungary: 8
    Country: Number of subjects enrolled
    Italy: 10
    Country: Number of subjects enrolled
    Korea, Republic of: 21
    Country: Number of subjects enrolled
    United States: 37
    Worldwide total number of subjects
    134
    EEA total number of subjects
    76
    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)
    81
    From 65 to 84 years
    53
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants (par.) who met eligibility criteria at Screening were then randomized to the treatment period. A total of 134 participants were randomized, and 130 participants entered the treatment period.

    Pre-assignment
    Screening details
    		 In the Randomized Phase (RP), participants were treated until disease progression (PD), death, or unacceptable adverse events were experienced. After PD in the RP, participants were given the option of crossing over to the alternative treatment arm in a Cross-over Phase (CP). Milestone of Completed = Par. with PD including death due to PD.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK1120212 2 mg in RP
    Arm description
    		 Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).
    Arm type
    		 Experimental

    Investigational medicinal product name
    trametinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2 mg once daily dosing

    Arm title
    		 Docetaxel 75 mg/m^2 in RP
    Arm description
    		 Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75 mg/m2 once every three weeks

    Number of subjects in period 1
    		GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Started
    89
    45
    Crossover Started
    23
    2
    Crossover Completed
    0
    0
    Completed
    0
    0
    Not completed
    89
    45
         Consent withdrawn by subject
    2
    1
         Physician decision
    1
    9
         Did not take study drug
    2
    2
         Adverse event, non-fatal
    20
    4
         PD including Death due to PD
    56
    28
         Study Closed/Terminated
    8
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK1120212 2 mg in RP
    Reporting group description
    		 Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).

    Reporting group title
    Docetaxel 75 mg/m^2 in RP
    Reporting group description
    		 Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.

    Reporting group values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP Total
    Number of subjects
    		 89 45 134
    Age categorical
    Units: Subjects
    Age continuous
    test
    Units: years
        arithmetic mean (standard deviation)
    		 61.4 ± 8.97 60.9 ± 10.06 -
    Gender categorical
    Units: Subjects
        Female
    		 43 22 65
        Male
    		 46 23 69
    Race
    Units: Subjects
        White - White/Caucasian/European Heritage
    		 73 32 105
        Asian - East Asian Heritage
    		 11 9 20
        White - Arabic/North African Heritage
    		 1 3 4
        African American/African Heritage
    		 3 0 3
        Asian - South East Asian Heritage
    		 0 1 1
        Missing
    		 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    GSK1120212 2 mg in RP
    Reporting group description
    		 Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).

    Reporting group title
    Docetaxel 75 mg/m^2 in RP
    Reporting group description
    		 Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.

    Subject analysis set title
    GSK1120212 2 mg in CP
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).

    Subject analysis set title
    Docetaxel 75 mg/m^2 in CP
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.

    Primary: Progression-Free Survival (PFS) as assessed by the investigator (INV)

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    End point title
    		 Progression-Free Survival (PFS) as assessed by the investigator (INV)
    End point description
    PFS is defined as the time from RAN until the earliest date of documented radiological PD or DT due to any cause. PD was assessed by the INV according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. For participants who did not have a documented date of PD or DT, PFS was censored at the date of the last adequate assessment. For participants who received subsequent anti-cancer therapy prior to the date of documented PD or DT, PFS was censored at the date of the last adequate assessment prior to the initiation of therapy.
    End point type
    Primary
    End point timeframe
    From randomization (RAN) until the earliest date of documented radiological disease progression (PD) or death (DT) due to any cause (maximum of 10.2 months)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    86 [1]
    43 [2]
    Units: Weeks
        median (confidence interval 95%)
    11.7 (7 to 12.4)
    11.4 (6.1 to 18.3)
    Notes
    [1] - Modified Intent-to-Treat (MITT) Population: all randomized participants with KRAS mutation-positive.
    [2] - Modified Intent-to-Treat (MITT) Population: all randomized participants with KRAS mutation-positive.
    Statistical analysis title
    		 Analysis 1
    Comparison groups
    Docetaxel 75 mg/m^2 in RP v GSK1120212 2 mg in RP
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.5197 [4]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.75
    Notes
    [3] - HRs were estimated using a Pike estimator. The HR from the stratified log-rank test was adjusted for gender (male versus female).
    [4] - P-value from the stratified log-rank was adjusted for gender (male versus female).

    Secondary: Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated clinical chemistry parameters: Randomized Phase

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    End point title
    		 Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated clinical chemistry parameters: Randomized Phase
    End point description
    Parameters summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G, G3, or G4 occurred. Parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy (OT)change from BL were summarized. Worst-case OT was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Only par. with data available at specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (BL); Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    87 [5]
    43 [6]
    Units: Participants
        Albumin, Increase to any G (IAG), n=86, 43
    57
    21
        Albumin, Increase to G3, n=86, 43
    4
    1
        Albumin, Increase to G4, n=86, 43
    0
    0
        ALKP, IAG, n=85, 43
    26
    3
        ALKP, Increase to G3, n =85, 43
    2
    1
        ALKP, Increase to G4, n=85, 43
    0
    0
        ALT, IAG, n=87, 43
    32
    7
        ALT, Increase to G3, n=87, 43
    3
    1
        ALT, Increase to G4, n=87, 43
    0
    0
        AST, IAG, n=86, 43
    55
    11
        AST, Increase to G3, n=86, 43
    1
    0
        AST, Increase to G4, n=86, 43
    0
    0
        Total bilirubin, IAG, n=85, 42
    3
    3
        Total bilirubin, Increase to G3, n=85, 42
    0
    0
        Total bilirubin, Increase to G4, n=85, 42
    0
    0
        Calcium (hypercalcemia), IAG, n =87, 43
    9
    3
        Calcium (hypercalcemia), Increase to G3, n=87, 43
    0
    0
        Calcium (hypercalcemia), Increase to G4, n=87, 43
    0
    0
        Calcium (hypocalcemia), IAG, n=87, 43
    4
    1
        Calcium (hypocalcemia), Increase to G3, n=87, 43
    0
    1
        Calcium (hypocalcemia), Increase to G4, n=87, 43
    1
    0
        Creatine kinase, IAG, n=1, 0
    0
    0
        Creatine kinase, Increase to G3, n=1, 0
    0
    0
        Creatine kinase, Increase to G4, n=1, 0
    0
    0
        Creatinine, IAG, n=87, 43
    12
    6
        Creatinine, Increase to G3, n=87, 43
    3
    1
        Creatinine, Increase to G4, n=87, 43
    0
    0
        Glucose (hyperglycemia), IAG, n=87, 43
    47
    24
        Glucose (hyperglycemia), Increase to G3, n=87, 43
    5
    2
        Glucose (hyperglycemia), Increase to G4, n=87, 43
    0
    0
        Glucose (hypoglycemia), IAG, n=87, 43
    4
    4
        Glucose (hypoglycemia), Increase to G3, n=87, 43
    0
    0
        Glucose (hypoglycemia), Increase to G4, n=87, 43
    0
    0
        Potassium (hyperkalemia), IAG, n=86, 43
    9
    4
        Potassium (hyperkalemia), Increase to G3, n=86, 43
    1
    1
        Potassium (hyperkalemia), Increase to G4n=86, 43
    0
    0
        Potassium (hypokalemia), IAG, n=86, 43
    8
    2
        Potassium (hypokalemia), Increase to G3, n=86, 43
    0
    0
        Potassium (hypokalemia), Increase to G4, n=86, 43
    0
    0
        Sodium (hypernatremia), IAG, n=87, 43
    12
    2
        Sodium (hypernatremia), Increase to G3, n=87, 43
    0
    0
        Sodium (hypernatremia), Increase to G4, n=87, 43
    0
    0
        Sodium (hyponatremia), IAG, n=87, 43
    16
    5
        Sodium (hyponatremia), Increase to G3, n=87, 43
    2
    1
        Sodium (hyponatremia), Increase to G4, n=87, 43
    0
    0
    Notes
    [5] - Safety Population: all participants that received at least one dose of study treatment.
    [6] - Safety Population: all participants that received at least one dose of study treatment.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated clinical chemistry parameters: Crossover Phase

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    End point title
    		 Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated clinical chemistry parameters: Crossover Phase
    End point description
    Clinical chemistry parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any grade, Grade 3, or Grade 4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Only participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
    End point values
    		 GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Number of subjects analysed
    23 [7]
    1 [8]
    Units: Participants
        Albumin, Increase to any G (IAG), n=23, 1
    15
    1
        Albumin, Increase to G3, n=23, 1
    4
    0
        Albumin, Increase to G4, n=23, 1
    0
    0
        ALKP, IAG, n=23, 1
    10
    0
        ALKP, Increase to G3, n =23, 1
    1
    0
        ALKP, Increase to G4, n=23, 1
    0
    0
        ALT, IAG, n=23, 1
    7
    0
        ALT, Increase to G3, n=23, 1
    1
    0
        ALT, Increase to G4, n=23, 1
    0
    0
        AST, IAG, n=23, 1
    9
    0
        AST, Increase to G3, n=23, 1
    1
    0
        AST, Increase to G4, n=23, 1
    0
    0
        Total bilirubin, IAG, n=22, 1
    1
    0
        Total bilirubin, Increase to G3, n=22, 1
    0
    0
        Total bilirubin, Increase to G4, n=22, 1
    0
    0
        Calcium (hypercalcemia), IAG, n =23, 1
    1
    0
        Calcium (hypercalcemia), Increase to G3, n=23, 1
    0
    0
        Calcium (hypercalcemia), Increase to G4, n=23, 1
    0
    0
        Calcium (hypocalcemia), IAG, n=23, 1
    0
    0
        Calcium (hypocalcemia), Increase to G3, n=23, 1
    0
    0
        Calcium (hypocalcemia), Increase to G4, n=23, 1
    0
    0
        Creatine kinase, IAG, n=1, 0
    1
    0
        Creatine kinase, Increase to G3, n=1, 0
    0
    0
        Creatine kinase, Increase to G4, n=1, 0
    0
    0
        Creatinine, IAG, n=23, 1
    3
    0
        Creatinine, Increase to G3, n=23, 1
    0
    0
        Creatinine, Increase to G4, n=23, 1
    0
    0
        Glucose (hyperglycemia), IAG, n=23, 1
    10
    0
        Glucose (hyperglycemia), Increase to G3, n=23, 1
    0
    0
        Glucose (hyperglycemia), Increase to G4, n=23, 1
    0
    0
        Glucose (hypoglycemia), IAG, n=23, 1
    1
    0
        Glucose (hypoglycemia), Increase to G3, n=23, 1
    0
    0
        Glucose (hypoglycemia), Increase to G4, n=23, 1
    0
    0
        Potassium (hyperkalemia), IAG, n=23, 1
    3
    0
        Potassium (hyperkalemia), Increase to G3, n=23, 1
    1
    0
        Potassium (hyperkalemia), Increase to G4, n=23, 1
    0
    0
        Potassium (hypokalemia), IAG, n=23, 1
    1
    0
        Potassium (hypokalemia), Increase to G3, n=23, 1
    0
    0
        Potassium (hypokalemia), Increase to G4, n=23, 1
    0
    0
        Sodium (hypernatremia), IAG, n=23, 1
    1
    0
        Sodium (hypernatremia), Increase to G3, n=23, 1
    0
    0
        Sodium (hypernatremia), Increase to G4, n=23, 1
    0
    0
        Sodium (hyponatremia), IAG, n=23, 1
    3
    0
        Sodium (hyponatremia), Increase to G3, n=23, 1
    2
    0
        Sodium (hyponatremia), Increase to G4, n=23, 1
    0
    0
    Notes
    [7] - Crossover Population: par. who, at the point of PD during RP, elected to enter the CP of the study.
    [8] - Crossover Population: par. who, at the point of PD during RP, elected to enter the CP of the study.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated hematology parameters: Randomized Phase

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    End point title
    		 Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated hematology parameters: Randomized Phase
    End point description
    Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased [inc]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased [dec]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    87 [9]
    43 [10]
    Units: Participants
        Haemoglobin (inc), IAG, n=87, 43
    0
    0
        Haemoglobin (inc), Increase to G3, n=87, 43
    0
    0
        Haemoglobin (inc), Increase to G4, n=87, 43
    0
    0
        Haemoglobin (anemia), IAG, n=86, 43
    34
    27
        Haemoglobin (anemia), Increase to G3, n=86, 43
    8
    3
        Haemoglobin (anemia), Increase to G4, n=86, 43
    0
    0
        Lymphocyte ct (inc), IAG, n=86, 43
    9
    2
        Lymphocyte ct (inc), Increase to G3, n=86, 43
    1
    0
        Lymphocyte ct (inc), Increase to G4, n=86, 43
    0
    0
        Lymphocyte ct (dec), IAG, n=85, 43
    18
    19
        Lymphocyte ct (dec), Increase to G3, n=85, 43
    4
    2
        Lymphocyte ct (dec), Increase to G4, n=85, 43
    0
    0
        ANC, IAG, n=86, 43
    5
    34
        ANC, Increase to G3, n=86, 43
    0
    13
        ANC, Increase to G4, n=86, 43
    0
    13
        Platelet ct, IAG, n=87, 43
    15
    3
        Platelet ct, Increase to G3, n=87, 43
    0
    0
        Platelet ct, Increase to G4, n=87, 43
    0
    0
        WBC, IAG, n=87, 43
    5
    33
        WBC, Increase to G3, n=87, 43
    0
    17
        WBC, Increase to G4, n=87, 43
    1
    0
    Notes
    [9] - Safety Population. Only participants with data available at the specified time points were analyzed.
    [10] - Safety Population. Only participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated hematology parameters: Crossover Phase

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    End point title
    		 Number of participants with the indicated worst-case on-therapy change from Baseline in the indicated hematology parameters: Crossover Phase
    End point description
    Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased [inc]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased [dec]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
    End point values
    		 GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Number of subjects analysed
    23 [11]
    1 [12]
    Units: Participants
        Haemoglobin (inc), IAG, n=23, 1
    0
    0
        Haemoglobin (inc), Increase to G3, n=23, 1
    0
    0
        Haemoglobin (inc), Increase to G4, n=23, 1
    0
    0
        Haemoglobin (anemia), IAG, n=23, 1
    12
    0
        Haemoglobin (anemia), Increase to G3, n=23, 1
    2
    0
        Haemoglobin (anemia), Increase to G4, n=23, 1
    0
    0
        Lymphocyte ct (inc), IAG, n=23, 1
    1
    0
        Lymphocyte ct (inc), Increase to G3, n=23, 1
    0
    0
        Lymphocyte ct (inc), Increase to G4, n=23, 1
    0
    0
        Lymphocyte ct (dec), IAG, n=23, 1
    3
    0
        Lymphocyte ct (dec), Increase to G3, n=23, 1
    0
    0
        Lymphocyte ct (dec), Increase to G4, n=23, 1
    0
    0
        ANC, IAG, n=19, 0
    0
    0
        ANC, Increase to G3, n=19, 0
    0
    0
        ANC, Increase to G4, n=19, 0
    0
    0
        Platelet ct, IAG, n=23, 1
    4
    0
        Platelet ct, Increase to G3, n=23, 1
    0
    0
        Platelet ct, Increase to G4, n=23, 1
    0
    0
        WBC, IAG, n=23, 1
    0
    0
        WBC, Increase to G3, n=23, 1
    0
    0
        WBC, Increase to G4, n=23, 1
    0
    0
    Notes
    [11] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    [12] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated clinical chemistry parameters: Randomized Phase

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    End point title
    		 Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated clinical chemistry parameters: Randomized Phase
    End point description
    Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    87 [13]
    43 [14]
    Units: Participants
        Lactate dehydrogenase, Decrease to low, n=87, 43
    1
    0
        Lactate dehydrogenase, CTN or no change, n=87, 43
    40
    23
        Lactate dehydrogenase, Increase to high, n=87, 43
    46
    20
        Total Protein, Decrease to low, n=86, 43
    31
    12
        Total Protein, CTN or no change, n=86, 43
    55
    31
        Total Protein, Increase to high, n=86, 43
    1
    0
        Urea/BUN, Decrease to low, n=87, 43
    0
    0
        Urea/BUN, CTN or no change, n=87, 43
    62
    34
        Urea/BUN, Increase to high, n=87,43
    25
    9
    Notes
    [13] - Safety Population. Only participants with data available at the specified time points were analyzed.
    [14] - Safety Population. Only participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated clinical chemistry parameters: Crossover Phase

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    End point title
    		 Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated clinical chemistry parameters: Crossover Phase
    End point description
    Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
    End point values
    		 GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Number of subjects analysed
    23 [15]
    1 [16]
    Units: Participants
        Lactate dehydrogenase, Decrease to low
    0
    0
        Lactate dehydrogenase, CTN or no change
    15
    1
        Lactate dehydrogenase, Increase to high
    8
    0
        Total Protein, Decrease to low
    15
    0
        Total Protein, CTN or no change
    8
    1
        Total Protein, Increase to high
    0
    0
        Urea/BUN, Decrease to low
    0
    0
        Urea/BUN, CTN or no change
    18
    1
        Urea/BUN, Increase to high
    5
    0
    Notes
    [15] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    [16] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated hematology parameters: Randomized Phase

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    End point title
    		 Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated hematology parameters: Randomized Phase
    End point description
    Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage [%]), basophils, eosinophils, metamyelocytes, monocytes, myelocytes, neutrophil bands (%). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    86 [17]
    43 [18]
    Units: Participants
        Atypical lymphs, Decrease to low, n=0, 3
    0
    0
        Atypical lymphs, CTN or no change, n=0, 3
    0
    0
        Atypical lymphs, Increase to high, n=0, 3
    0
    3
        Atypical lymphs (%), Decrease to low, n =0, 3
    0
    0
        Atypical lymphs (%), CTN or no change, n=0, 3
    0
    0
        Atypical lymphs (%), Increase to high, n=0, 3
    0
    3
        Basophils, Decrease to low, n=86, 43
    0
    0
        Basophils, CTN or no change, n=86, 43
    82
    41
        Basophils, Increase to high, n=86,43
    4
    2
        Eosinophils, Decrease to low, n=86, 43
    1
    1
        Eosinophils, CTN or no change, n=86, 43
    77
    42
        Eosinophils, Increase to high, n=86, 43
    9
    0
        Metamyelocytes, Decrease to low, n=1, 7
    0
    0
        Metamyelocytes, CTN or no change, n=1, 7
    0
    0
        Metamyelocytes, Increase to high, n=1, 7
    1
    7
        Monocytes, Decrease to low, n=86, 43
    3
    20
        Monocytes, CTN or no change, n=86, 43
    78
    18
        Monocytes, Increase to high, n=86, 43
    5
    9
        Myelocytes, Decrease to low, n=1, 9
    0
    0
        Myelocytes, CTN or no change, n=1, 9
    0
    1
        Myelocytes, Increase to high, n=1, 9
    1
    8
        Neutrophil Bands (%), Decrease to low, n=1, 4
    0
    0
        Neutrophil Bands (%), CTN or no change, n=1, 4
    1
    3
        Neutrophil Bands (%), Increase to high, n=1, 4
    0
    1
    Notes
    [17] - Safety Population. Only participants with data available at the specified time points were analyzed.
    [18] - Safety Population. Only participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated hematology parameters: Crossover Phase

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    End point title
    		 Number of participants with the indicated worst-case on-therapy change from Baseline with respect to normal ranges in the indicated hematology parameters: Crossover Phase
    End point description
    Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage [%]), basophils, eosinophils, metamyelocytes, monocytes, and myelocytes. Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
    End point values
    		 GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Number of subjects analysed
    23 [19]
    1 [20]
    Units: Participants
        Atypical lymphs, Decrease to low, n=3, 1
    0
    0
        Atypical lymphs, CTN or no change, n=3, 1
    1
    0
        Atypical lymphs, Increase to high, n=3, 1
    2
    1
        Atypical lymphs (%), Decrease to low, n=3, 1
    0
    0
        Atypical lymphs (%), CTN or no change, n=3, 1
    1
    0
        Atypical lymphs (%), Increase to high, n=3, 1
    2
    1
        Basophils, Decrease to low, n=23, 1
    0
    0
        Basophils, CTN or no change, n=23, 1
    23
    1
        Basophils, Increase to high, n=23, 1
    0
    0
        Eosinophils, Decrease to low, n=23, 1
    0
    0
        Eosinophils, CTN or no change, n=23, 1
    23
    1
        Eosinophils, Increase to high, n=23, 1
    0
    0
        Metamyelocytes, Decrease to low, n=1, 1
    0
    0
        Metamyelocytes, CTN or no change, n=1, 1
    0
    0
        Metamyelocytes, Increase to high, n=1, 1
    1
    1
        Monocytes, Decrease to low, n=23, 1
    1
    0
        Monocytes, CTN or no change, n=23, 1
    20
    0
        Monocytes, Increase to high, n=23, 1
    2
    1
        Myelocytes, Decrease to low, n=3, 1
    0
    0
        Myelocytes, CTN or no change, n=3, 1
    0
    0
        Myelocytes, Increase to high, n=3, 1
    3
    1
    Notes
    [19] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    [20] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with any serious adverse event (SAE) or non-serious adverse event (AE): Randomized Phase

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    End point title
    		 Number of participants with any serious adverse event (SAE) or non-serious adverse event (AE): Randomized Phase
    End point description
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
    End point type
    Secondary
    End point timeframe
    From randomization until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 19 months)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    87 [21]
    43 [22]
    Units: Participants
        Any AE
    87
    43
        Any SAE
    32
    9
    Notes
    [21] - Safety Population
    [22] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with any SAE or non-serious AE: Crossover Phase

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    End point title
    		 Number of participants with any SAE or non-serious AE: Crossover Phase
    End point description
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
    End point type
    Secondary
    End point timeframe
    From the date of the first dose of study treatment in the Crossover Phase until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 12 months)
    End point values
    		 GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Number of subjects analysed
    23 [23]
    2 [24]
    Units: Participants
        Any AE
    22
    2
        Any SAE
    12
    1
    Notes
    [23] - Crossover Population
    [24] - Crossover Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase

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    End point title
    		 Change from Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase
    End point description
    Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle thereafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    87 [25]
    43 [26]
    Units: millimeters of mercury (mmHg)
    arithmetic mean (standard deviation)
        SBP, Worst-case on-therapy
    13.5 ± 16.63
    3.1 ± 13.71
        DBP, Worst-case on-therapy
    10.7 ± 9.95
    2.5 ± 7.34
    Notes
    [25] - Safety Population. Only participants with data available at the specified time points were analyzed.
    [26] - Safety Population. Only participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in SBP and DBP: Crossover Phase

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    End point title
    		 Change from Baseline in SBP and DBP: Crossover Phase
    End point description
    Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline. The standard deviation could not be calculated since only one participant was analyzed in this treatment arm at this time point; therefore, 99999 was entered which represents NA.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
    End point values
    		 GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Number of subjects analysed
    23 [27]
    1 [28]
    Units: mmHg
    arithmetic mean (standard deviation)
        SBP, Worst-case on-therapy
    8.7 ± 15.95
    -15 ± 99999
        DBP, Worst-case on-therapy
    8.3 ± 12.28
    -12 ± 99999
    Notes
    [27] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    [28] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in heart rate: Randomized Phase

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    End point title
    		 Change from Baseline in heart rate: Randomized Phase
    End point description
    Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    87 [29]
    43 [30]
    Units: Beats per minute
        arithmetic mean (standard deviation)
    10.4 ± 14.23
    13.2 ± 9.31
    Notes
    [29] - Safety Population. Only participants with data available at the specified time points were analyzed.
    [30] - Safety Population. Only participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in heart rate: Crossover Phase

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    End point title
    		 Change from Baseline in heart rate: Crossover Phase
    End point description
    Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline. The standard deviation could not be calculated since only one participant was analyzed in this treatment arm at this time point; therefore, 99999 was entered which represents NA.
    End point type
    Secondary
    End point timeframe
    Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
    End point values
    		 GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Number of subjects analysed
    23 [31]
    1 [32]
    Units: Beats per minute
        arithmetic mean (standard deviation)
    8.5 ± 11.46
    5 ± 99999
    Notes
    [31] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    [32] - Crossover Population. Only par. with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with a best response of either a complete response (CR) or partial response (PR) as assessed by the investigator: Randomized Phase

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    End point title
    		 Number of participants with a best response of either a complete response (CR) or partial response (PR) as assessed by the investigator: Randomized Phase
    End point description
    Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 millimeters [mm] in the short axis; without the appearance of new lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). Participants with unknown or missing response were treated as non-responders.
    End point type
    Secondary
    End point timeframe
    From randomization until the first documented evidence of a CR or PR (maximum of 10.2 months)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    86 [33]
    43 [34]
    Units: Participants
        CR
    0
    0
        PR
    10
    5
    Notes
    [33] - MITT Population
    [34] - MITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with a best response of either a CR or PR as assessed by the investigator: Crossover Phase

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    End point title
    		 Number of participants with a best response of either a CR or PR as assessed by the investigator: Crossover Phase
    End point description
    Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 millimeters [mm] in the short axis; without the appearance of new lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). Participants with unknown or missing response were treated as non-responders.
    End point type
    Secondary
    End point timeframe
    From the date of the first dose of study treatment in the Crossover Phase until the first documented evidence of a CR or PR (maximum of 4 months)
    End point values
    		 GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Number of subjects analysed
    23 [35]
    2 [36]
    Units: Participants
        CR
    0
    0
        PR
    1
    0
    Notes
    [35] - Crossover Population
    [36] - Crossover Population
    No statistical analyses for this end point

    Secondary: Duration of response (DOR) as assessed by the investigator: Randomized Phase

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    End point title
    		 Duration of response (DOR) as assessed by the investigator: Randomized Phase
    End point description
    DOR was assessed by the investigator for par. with CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 mm in the short axis; without the appearance of new lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). DOR is defined as the time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. There were a limited number of par. with a CR or PR who progressed or died; therefore, the upper limit (UL) of the CI could not be estimated (99999=NA).
    End point type
    Secondary
    End point timeframe
    Time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause (maximum of 10.2 months)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    10 [37]
    5 [38]
    Units: Weeks
        arithmetic mean (confidence interval 95%)
    6.7 (2.7 to 99999)
    12.4 (7.1 to 17.3)
    Notes
    [37] - MITT Population. Only participants who achieved a CR or PR were analyzed for duration of response.
    [38] - MITT Population. Only participants who achieved a CR or PR were analyzed for duration of response.
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, OS was censored at the date of last contact. Statistics for the median is missing because an insufficient number of participants reached the milestone, making calculation of this statistic inappropriate or impossible (99999=NA).
    End point type
    Secondary
    End point timeframe
    Time interval between the date of randomization and the date of death due to any cause (maximum of 22 months)
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    86 [39]
    43 [40]
    Units: Months
        median (confidence interval 95%)
    8.1 (6.8 to 10)
    9.9 (5 to 99999)
    Notes
    [39] - MITT Population
    [40] - MITT Population
    No statistical analyses for this end point

    Secondary: GSK1120212 plasma pharmacokinetic (PK) concentration

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    End point title
    		 GSK1120212 plasma pharmacokinetic (PK) concentration
    End point description
    Blood samples for PK analysis of GSK1120212 were collected at the following time points: Cycle 1 (Study Day 15), Cycle 2 (Study Day 22), Cycle 3 (Study Day 43), and Cycle 4 (Study Day 64). Post-dose PK samples collected on Day 15 of Cycle 1 occurred at least 1 hour apart. Participants were instructed to withhold the dose of GSK1120212 until after blood for PK samples had been drawn. Pre-dose samples were taken 15 minutes or less prior to taking the next dose (i.e., trough).
    End point type
    Secondary
    End point timeframe
    Day 15 of Cycle 1: pre-dose; 0.5-2 hours, 2-4 hours, and 4-8 hours post-dose; Day 1 of Cycle 2, Cycle 3 and Cycle 4: pre-dose
    End point values
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP
    Number of subjects analysed
    80 [41]
    0 [42]
    Units: Nanograms (ng)/milliliter (mL)
    arithmetic mean (standard deviation)
        Cycle 1, Day 15, pre-dose, n=80
    16.1 ± 5.31
    ±
        Cycle 1, Day 15, 0.5-2 hours post-dose, n=78
    21.5 ± 8.59
    ±
        Cycle 1, Day 15, 2-4 hours post-dose, n=77
    29.7 ± 22.9
    ±
        Cycle 1, Day 15, 4-8 hours post-dose, n=78
    24.8 ± 7.8
    ±
        Cycle 2, Day 1, pre-dose, n=75
    16.7 ± 6.95
    ±
        Cycle 3, Day 1, pre-dose, n=60
    12.9 ± 7.19
    ±
        Cycle 4, Day 1, pre-dose, n=38
    13.9 ± 6.49
    ±
    Notes
    [41] - PK Population. Only participants with data available at the specified time points were analyzed.
    [42] - PK Population. Only participants with data available at the specified time points were analyzed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious Adverse Events (SAEs) and non-serious AEs were collected from the first dose of study treatment until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy (maximum of 19 months).
    Adverse event reporting additional description
    SAEs and non-serious AEs were collected in members of the Safety Population (all participants who received at least one dose of study treatment) and the Crossover Population (participants who, at the point of disease progression during the Randomized Phase, elected to enter the crossover portion of the study).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    GSK1120212 2 mg in RP
    Reporting group description
    		 Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared [mg/m^2]), and continuing in the Cross-over Phase (CP).

    Reporting group title
    Docetaxel 75 mg/m^2 in RP
    Reporting group description
    		 Participants received docetaxel 75 mg per meters squared (m^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.

    Reporting group title
    GSK1120212 2 mg in CP
    Reporting group description
    		 Participants who experienced disease progression in the RP were given the option of crossing over to GSK1120212 2 mg and continuing in the Cross-over Phase (CP).

    Reporting group title
    Docetaxel 75 mg/m^2 in CP
    Reporting group description
    		 Participants who experienced disease progression in the RP were given the option of crossing over to docetaxel 75 mg/m^2 and continuing in the CP.

    Serious adverse events
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Total subjects affected by serious adverse events
         subjects affected / exposed
    32 / 87 (36.78%)
    9 / 43 (20.93%)
    12 / 23 (52.17%)
    1 / 2 (50.00%)
         number of deaths (all causes)
    4
    0
    1
    0
         number of deaths resulting from adverse events
    1
    0
    1
    0
    Vascular disorders
    Thrombosis
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    3 / 87 (3.45%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    2 / 23 (8.70%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 43 (2.33%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Radiation pneumonitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    1 / 2 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 43 (2.33%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 43 (2.33%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sigmoiditis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis exfoliative
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash generalised
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angioedema
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    2 / 87 (2.30%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    6 / 87 (6.90%)
    1 / 43 (2.33%)
    2 / 23 (8.70%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    4 / 87 (4.60%)
    1 / 43 (2.33%)
    2 / 23 (8.70%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jiroveci infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash pustular
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         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
    		 GSK1120212 2 mg in RP Docetaxel 75 mg/m^2 in RP GSK1120212 2 mg in CP Docetaxel 75 mg/m^2 in CP
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    87 / 87 (100.00%)
    43 / 43 (100.00%)
    20 / 23 (86.96%)
    1 / 2 (50.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    30 / 87 (34.48%)
    8 / 43 (18.60%)
    2 / 23 (8.70%)
    0 / 2 (0.00%)
         occurrences all number
    36
    9
    2
    0
    Hypotension
         subjects affected / exposed
    9 / 87 (10.34%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    9
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    24 / 87 (27.59%)
    12 / 43 (27.91%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    27
    16
    0
    0
    Asthenia
         subjects affected / exposed
    20 / 87 (22.99%)
    11 / 43 (25.58%)
    4 / 23 (17.39%)
    1 / 2 (50.00%)
         occurrences all number
    23
    15
    4
    1
    Oedema peripheral
         subjects affected / exposed
    19 / 87 (21.84%)
    5 / 43 (11.63%)
    7 / 23 (30.43%)
    0 / 2 (0.00%)
         occurrences all number
    24
    5
    9
    0
    Pyrexia
         subjects affected / exposed
    15 / 87 (17.24%)
    4 / 43 (9.30%)
    3 / 23 (13.04%)
    0 / 2 (0.00%)
         occurrences all number
    20
    5
    6
    0
    Mucosal inflammation
         subjects affected / exposed
    6 / 87 (6.90%)
    6 / 43 (13.95%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    10
    7
    0
    0
    Face oedema
         subjects affected / exposed
    6 / 87 (6.90%)
    2 / 43 (4.65%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    2
    0
    0
    Oedema
         subjects affected / exposed
    6 / 87 (6.90%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    1
    0
    0
    Chills
         subjects affected / exposed
    6 / 87 (6.90%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    28 / 87 (32.18%)
    8 / 43 (18.60%)
    4 / 23 (17.39%)
    1 / 2 (50.00%)
         occurrences all number
    28
    9
    4
    1
    Cough
         subjects affected / exposed
    24 / 87 (27.59%)
    8 / 43 (18.60%)
    6 / 23 (26.09%)
    0 / 2 (0.00%)
         occurrences all number
    26
    8
    8
    0
    Haemoptysis
         subjects affected / exposed
    7 / 87 (8.05%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    8
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    3 / 87 (3.45%)
    5 / 43 (11.63%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    5
    0
    0
    Productive cough
         subjects affected / exposed
    2 / 87 (2.30%)
    5 / 43 (11.63%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    5
    0
    0
    Epistaxis
         subjects affected / exposed
    6 / 87 (6.90%)
    0 / 43 (0.00%)
    2 / 23 (8.70%)
    0 / 2 (0.00%)
         occurrences all number
    6
    0
    2
    0
    Pleural effusion
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    2 / 23 (8.70%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 87 (0.00%)
    3 / 43 (6.98%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 87 (6.90%)
    9 / 43 (20.93%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    9
    0
    0
    Confusional state
         subjects affected / exposed
    5 / 87 (5.75%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    5
    0
    0
    0
    Anxiety
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 43 (6.98%)
    1 / 23 (4.35%)
    1 / 2 (50.00%)
         occurrences all number
    3
    3
    1
    1
    Investigations
    Weight decreased
         subjects affected / exposed
    9 / 87 (10.34%)
    2 / 43 (4.65%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    9
    2
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 87 (6.90%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    7
    1
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    7 / 43 (16.28%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    8
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 43 (6.98%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Ejection fraction decreased
         subjects affected / exposed
    5 / 87 (5.75%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    0
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    3 / 43 (6.98%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    6 / 87 (6.90%)
    5 / 43 (11.63%)
    2 / 23 (8.70%)
    0 / 2 (0.00%)
         occurrences all number
    6
    7
    2
    0
    Neuropathy peripheral
         subjects affected / exposed
    2 / 87 (2.30%)
    9 / 43 (20.93%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    10
    0
    0
    Dysgeusia
         subjects affected / exposed
    3 / 87 (3.45%)
    5 / 43 (11.63%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    5
    0
    0
    Paraesthesia
         subjects affected / exposed
    1 / 87 (1.15%)
    3 / 43 (6.98%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    4
    0
    0
    Headache
         subjects affected / exposed
    5 / 87 (5.75%)
    2 / 43 (4.65%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    5
    2
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    18 / 87 (20.69%)
    8 / 43 (18.60%)
    5 / 23 (21.74%)
    0 / 2 (0.00%)
         occurrences all number
    18
    11
    6
    0
    Neutropenia
         subjects affected / exposed
    1 / 87 (1.15%)
    15 / 43 (34.88%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    16
    0
    0
    Leukopenia
         subjects affected / exposed
    1 / 87 (1.15%)
    5 / 43 (11.63%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    5
    0
    0
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 43 (6.98%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    3
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    44 / 87 (50.57%)
    9 / 43 (20.93%)
    11 / 23 (47.83%)
    1 / 2 (50.00%)
         occurrences all number
    60
    12
    20
    1
    Nausea
         subjects affected / exposed
    30 / 87 (34.48%)
    12 / 43 (27.91%)
    5 / 23 (21.74%)
    0 / 2 (0.00%)
         occurrences all number
    37
    18
    8
    0
    Constipation
         subjects affected / exposed
    18 / 87 (20.69%)
    8 / 43 (18.60%)
    5 / 23 (21.74%)
    0 / 2 (0.00%)
         occurrences all number
    21
    11
    6
    0
    Vomiting
         subjects affected / exposed
    20 / 87 (22.99%)
    6 / 43 (13.95%)
    5 / 23 (21.74%)
    0 / 2 (0.00%)
         occurrences all number
    27
    7
    5
    0
    Dry mouth
         subjects affected / exposed
    13 / 87 (14.94%)
    1 / 43 (2.33%)
    3 / 23 (13.04%)
    0 / 2 (0.00%)
         occurrences all number
    14
    1
    3
    0
    Abdominal pain upper
         subjects affected / exposed
    9 / 87 (10.34%)
    2 / 43 (4.65%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    12
    2
    0
    0
    Stomatitis
         subjects affected / exposed
    8 / 87 (9.20%)
    3 / 43 (6.98%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    8
    3
    0
    0
    Abdominal pain
         subjects affected / exposed
    5 / 87 (5.75%)
    3 / 43 (6.98%)
    1 / 23 (4.35%)
    1 / 2 (50.00%)
         occurrences all number
    7
    3
    1
    1
    Gastritis
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    1
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    51 / 87 (58.62%)
    6 / 43 (13.95%)
    7 / 23 (30.43%)
    0 / 2 (0.00%)
         occurrences all number
    90
    6
    9
    0
    Alopecia
         subjects affected / exposed
    2 / 87 (2.30%)
    17 / 43 (39.53%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    17
    0
    0
    Pruritus
         subjects affected / exposed
    17 / 87 (19.54%)
    2 / 43 (4.65%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    20
    7
    0
    0
    Dry skin
         subjects affected / exposed
    15 / 87 (17.24%)
    2 / 43 (4.65%)
    3 / 23 (13.04%)
    0 / 2 (0.00%)
         occurrences all number
    15
    2
    3
    0
    Dermatitis acneiform
         subjects affected / exposed
    11 / 87 (12.64%)
    2 / 43 (4.65%)
    2 / 23 (8.70%)
    0 / 2 (0.00%)
         occurrences all number
    11
    2
    3
    0
    Skin fissures
         subjects affected / exposed
    8 / 87 (9.20%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    11
    0
    0
    0
    Nail disorder
         subjects affected / exposed
    2 / 87 (2.30%)
    3 / 43 (6.98%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    6 / 87 (6.90%)
    10 / 43 (23.26%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    19
    0
    0
    Back pain
         subjects affected / exposed
    9 / 87 (10.34%)
    6 / 43 (13.95%)
    2 / 23 (8.70%)
    1 / 2 (50.00%)
         occurrences all number
    9
    7
    2
    1
    Arthralgia
         subjects affected / exposed
    3 / 87 (3.45%)
    5 / 43 (11.63%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    4
    7
    0
    0
    Muscular weakness
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    1 / 23 (4.35%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    1
    2
    Infections and infestations
    Paronychia
         subjects affected / exposed
    7 / 87 (8.05%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    7
    1
    0
    0
    Lung infection
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 43 (0.00%)
    0 / 23 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    5 / 87 (5.75%)
    2 / 43 (4.65%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    2
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    21 / 87 (24.14%)
    7 / 43 (16.28%)
    5 / 23 (21.74%)
    0 / 2 (0.00%)
         occurrences all number
    22
    8
    5
    0
    Hypoalbuminaemia
         subjects affected / exposed
    9 / 87 (10.34%)
    1 / 43 (2.33%)
    4 / 23 (17.39%)
    0 / 2 (0.00%)
         occurrences all number
    9
    1
    5
    0
    Hyperglycaemia
         subjects affected / exposed
    5 / 87 (5.75%)
    2 / 43 (4.65%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    5
    2
    0
    0
    Dehydration
         subjects affected / exposed
    5 / 87 (5.75%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    5
    1
    0
    0
    Hypokalaemia
         subjects affected / exposed
    5 / 87 (5.75%)
    1 / 43 (2.33%)
    0 / 23 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Oct 2012
    The protocol was amended to consider the recommendation of the independent Safety Review Committee following their review of the results of the pre-specified interim analysis of efficacy and safety. Following the iSRC findings from the pre-planned interim analysis, the GSK1120212 arm was modified. All subjects currently receiving GSK1120212 were permanently discontinued from GSK1120212 (except in subjects deriving clinical benefit without severe drug-induced toxicity). The option to crossover to the alternate treatment arm at disease progression was no longer allowed. The study was considered complete when 50% of subjects with KRAS mutant positive disease have died.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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