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    Clinical Trial Results:
    An Open-Label, Multi-Center, Randomized Phase 1B/2 Study of PF-05212384 Plus 5-Fluorouracil-Leucovorin- Irinotecan (FOLFIRI) Versus Bevacizumab Plus FOLFIRI in Metastatic Colorectal Cancer

    Summary
    EudraCT number
    		 2013-002096-18
    Trial protocol
    		 BE   IT   ES  
    Global end of trial date
    05 Aug 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Jul 2016
    First version publication date
    30 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B2151007
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClincialTrials.gov Call Center, Pfizer Inc., 1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClincialTrials.gov Call Center, Pfizer Inc., 1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 Feb 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Aug 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Aug 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objectives were to assess safety and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of the combination of PF-05212384 plus Folfiri (Phase 1B) and to demonstrate that the combination of PF-05212384 plus FOLFIRI is superior to the combination of bevacizumab plus FOLFIRI in prolonging progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) who have progressed on prior oxaliplatin-containing regimen (Phase 2).
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Feb 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    United States: 13
    Country: Number of subjects enrolled
    Canada: 3
    Worldwide total number of subjects
    18
    EEA total number of subjects
    2
    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)
    12
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Approximately 190 patients were planned to be enrolled to the study.

    Pre-assignment
    Screening details
    		 Patients >=18 years were required to have histologically proven diagnosis of colorectal cancer and evidence of metastatic disease not amenable to potentially curative treatment.

    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
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
    Arm description
    		 Subjects received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-05212384 90 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous (IV) infusion of PF-05212384 90 mg weekly

    Arm title
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
    Arm description
    		 Subjects received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-05212384 90 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous (IV) infusion of PF-05212384 90 mg weekly

    Arm title
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
    Arm description
    		 Subjects received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-05212384 110 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous (IV) infusion of PF-05212384 110 mg weekly

    Arm title
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
    Arm description
    		 Subjects received intravenous (IV) infusion of PF-05212384 130 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-05212384 130 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous (IV) infusion of PF-05212384 130 mg weekly

    Arm title
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Arm description
    		 Subjects received intravenous (IV) infusion of PF-05212384 150 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-05212384 150 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous (IV) infusion of PF-05212384 150 mg weekly

    Number of subjects in period 1
    		PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Started
    3
    4
    3
    5
    3
    Completed
    3
    3
    3
    1
    1
    Not completed
    0
    1
    0
    4
    2
         Adverse event, serious fatal
    -
    -
    -
    1
    -
         Consent withdrawn by subject
    -
    1
    -
    -
    2
         Unspecified
    -
    -
    -
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 130 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 150 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4 Total
    Number of subjects
    		 3 4 3 5 3 18
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0
        Adults (18-64 years)
    		 3 3 1 2 3 12
        From 65-84 years
    		 0 1 2 3 0 6
        85 years and over
    		 0 0 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 41.7 ± 11.7 54.3 ± 10.1 63.3 ± 11.6 65.8 ± 9 54.3 ± 5.5 -
    Gender, Male/Female
    Units: Participants
        FEMALE
    		 1 3 0 0 3 7
        MALE
    		 2 1 3 5 0 11

    End points

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    End points reporting groups
    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 130 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Reporting group description
    		 Subjects received intravenous (IV) infusion of PF-05212384 150 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Primary: Percentage of Subjects with Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy

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    End point title
    		 Percentage of Subjects with Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy [1]
    End point description
    DLTs were classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and defined as any of the following events judged to be attributed to the combination of PF-05212384 plus FOLFIRI: hematologic (febrile neutropenia or a sustained temperature >=38 degrees Celcius for >1 hour, grade >=3 neutropenic infection, grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia); non-hematologic (grade >=2 pneumonitis, grade >=3 toxicities, toxicities which resulted in failure to deliver at least 75% of the planned total dose of PF-05212384 and/or 50% of the planned total dose of FOLFIRI during the first cycle, toxicities which resulted in delay of start of Cycle 2 by >2 weeks of scheduled day (Day 43 of study), Grade 3 QTc prolongation).
    End point type
    Primary
    End point timeframe
    Day 1 up to Day 28
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were planned for this primary endpoint. For the Phase 1b, the number of subjects with a DLT was summarized by dose level.
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: percentage of subjects
        number (not applicable)
    0
    0
    0
    20
    66.7
    No statistical analyses for this end point

    Primary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS) [2]
    End point description
    Progression-free survival was the time from randomization date to the date of first documentation of progression or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) up to disease progression or death whichever occurred first (up to 18 months)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: PFS was only to be assessed in the Phase 2 portion of the study. As this study was terminated prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2.
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    0 [3]
    0 [4]
    0 [5]
    0 [6]
    0 [7]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [3] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [4] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [5] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [6] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [7] - Study was terminated prior to the Phase 2 portion and no data were collected.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Best Overall Response (Phase 1B)

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    End point title
    		 Number of Subjects With Best Overall Response (Phase 1B)
    End point description
    Best overall response is defined as the best response recorded from randomization (or first dose for patients in the Phase 1B) until disease progression, death, start of new anti-cancer treatment or end of study. The categories for best overall response include: complete response (CR) (complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 millimeters (mm)); partial response (PR) (at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); stable disease (SD) (not qualify for CR, PR or Progression); progressive disease (PD) (20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm); indeterminate (IND) (progression has not been documented).
    End point type
    Secondary
    End point timeframe
    Every 8 weeks from Cycle 1 Day 1 until 28 days of last dose
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    2
    4
    3
    5
    3
    Units: subjects
        PD
    2
    2
    0
    1
    1
        SD
    0
    2
    2
    3
    0
        PR
    0
    0
    1
    0
    0
        Indeterminant
    0
    0
    0
    1
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects with All Causalities Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness

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    End point title
    		 Number of Subjects with All Causalities Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
    End point description
    An AE was any untoward medical occurrence without regard to causality in a subject who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An AE was considered treatment emergent if the event occurred for the first time after the start of study treatment and within 28 days after final dose of study treatment and was not seen prior to the start of treatment; or the event was seen prior to the start of treatment but increased in CTCAE version 4.0 grade after the start of study treatment and within 28 days after final dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline up to final study evaluation (within 28 days of last dose)
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: subjects
        Number (#) of Subjects with AEs
    3
    4
    3
    5
    3
        # of Subjects with SAEs
    0
    0
    2
    2
    3
        # of Subjects with Grade 3 or 4 AEs
    0
    3
    3
    3
    3
        # of Subjects with Grade 5 AEs
    0
    0
    0
    0
    0
        # of Subjects D/C'd Study Due to AEs
    0
    0
    0
    0
    0
        # of Subjects D/C'd PF-05212384 Due to AEs
    0
    0
    0
    0
    1
        Number of Subjects D/C'd FOLFIRI Due to AEs
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with All Causalities AEs by System Organ Class (SOC)

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    End point title
    		 Number of Subjects with All Causalities AEs by System Organ Class (SOC)
    End point description
    An AE was any untoward medical occurrence without regard to causality in a subject who received study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to final study evaluation (within 28 days of last dose)
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: subjects
        Blood and lymphatic system disorders
    0
    2
    0
    1
    0
        Eye disorders
    0
    1
    0
    0
    1
        Gastrointestinal disorders
    3
    4
    3
    5
    3
        General disorders & administration site conditions
    2
    2
    2
    4
    2
        Hepatobiliary disorders
    0
    0
    0
    1
    0
        Immune system disorders
    0
    0
    1
    0
    0
        Infections and infestations
    1
    3
    1
    1
    1
        Injury, poisoning and procedural complications
    0
    3
    0
    0
    0
        Investigations
    1
    4
    1
    2
    2
        Metabolism and nutrition disorders
    2
    3
    1
    3
    2
        Musculoskeletal and connective tissue disorders
    1
    4
    1
    1
    1
        Nervous system disorders
    0
    2
    3
    2
    1
        Psychiatric disorders
    3
    2
    0
    0
    2
        Renal and urinary disorders
    0
    2
    0
    1
    0
        Respiratory, thoracic and mediastinal disorders
    1
    1
    3
    3
    1
        Skin and subcutaneous tissue disorders
    1
    3
    2
    2
    3
        Vascular disorders
    0
    1
    1
    1
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with Treatment-Emergent AEs by Worst On-Study Grade

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    End point title
    		 Number of Subjects with Treatment-Emergent AEs by Worst On-Study Grade
    End point description
    An AE was any untoward medical occurrence without regard to causality in a subject who received study drug. AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria.
    End point type
    Secondary
    End point timeframe
    Baseline up to final study evaluation (within 28 days of last dose)
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: subjects
        Any AEs, Grade 1
    0
    0
    0
    1
    0
        Any AEs, Grade 2
    3
    1
    0
    1
    0
        Any AEs, Grade 3
    0
    3
    3
    2
    3
        Any AEs, Grade 4
    0
    0
    0
    1
    0
        Any AEs, Grade 5
    0
    0
    0
    0
    0
        Any AEs, total
    3
    4
    3
    5
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects with Hematological Test Abnormalities

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    End point title
    		 Number of Subjects with Hematological Test Abnormalities
    End point description
    Number of subjects with NCI CTCAE version 4.0 grade 1 to 4 hematological test abnormalities.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 15 of each cycle
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    2
    Units: subjects
        Anemia
    3
    4
    3
    5
    2
        Hemoglobin increased
    0
    0
    0
    0
    0
        Lymphocyte count increased
    0
    1
    0
    0
    0
        Lymphopenia
    2
    2
    2
    3
    0
        Neutrophils (Absolute)
    0
    4
    2
    2
    2
        Platelets
    0
    2
    0
    2
    0
        White blood cells
    1
    3
    3
    3
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects with Coagulation Test Abnormalities

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    End point title
    		 Number of Subjects with Coagulation Test Abnormalities
    End point description
    Number of subjects with NCI CTCAE version 4.0 grade 1 to 4 Coagulation test abnormalities.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: subjects
        Partial thromboplastin time (N=3, 2, 3, 5, 2)
    1
    0
    1
    2
    2
        Prothrombin time (PT) (N=3, 1,2, 5, 1)
    1
    0
    2
    1
    1
        PT INR (N=3, 2, 3, 5, 2)
    1
    0
    2
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with Chemistry Test Abnormalities

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    End point title
    		 Number of Subjects with Chemistry Test Abnormalities
    End point description
    Number of subjects with NCI CTCAE version 4.0 grade 1 to 4 Chemistry test abnormalities.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 15 of each cycle
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    2
    3
    5
    2
    Units: subjects
        Alanine aminotransferase
    0
    1
    1
    3
    1
        Alkaline phosphatase
    3
    2
    0
    3
    1
        Aspartate aminotransferase
    2
    2
    2
    4
    1
        Bilirubin (total)
    0
    2
    0
    1
    0
        Creatinine
    1
    2
    3
    4
    2
        Hyperglycemia
    2
    3
    1
    5
    2
        Hypermagnesemia
    0
    0
    1
    0
    0
        Hypoalbuminemia
    2
    2
    0
    3
    1
        Hypocalcemia
    0
    0
    0
    2
    0
        Hypoglycemia
    1
    0
    0
    0
    0
        Hypokalemia
    2
    2
    1
    0
    1
        Hypomagnesemia
    0
    1
    1
    1
    0
        Hyponatremia
    3
    2
    1
    4
    0
        Hypohphosphatemia
    1
    0
    0
    1
    0
        Hyperkalemia
    0
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Urinalysis Test Abnormalities

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    End point title
    		 Number of Subjects with Urinalysis Test Abnormalities
    End point description
    Number of subjects with NCI CTCAE version 4.0 grade 1 to 4 Urinalysis test abnormalities.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    2
    Units: subjects
    2
    1
    1
    2
    2
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil
    End point description
    Maximum Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil
    End point type
    Secondary
    End point timeframe
    PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: nanogram (ng)/milliliter (mL)
    geometric mean (geometric coefficient of variation)
        PF-05212384 (n=3,4,2,5,3)
    8245 ± 25
    6554 ± 66
    33470 ± 99999
    8222 ± 35
    10250 ± 11
        Irinotecan (n=3,4,1,5,3)
    1782 ± 4
    1323 ± 43
    1550 ± 99999
    1585 ± 17
    1755 ± 6
        Fluorouracil (n=3,4,1,4,3)
    18390 ± 85
    18950 ± 41
    44000 ± 99999
    26790 ± 18
    26920 ± 3
    No statistical analyses for this end point

    Secondary: Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil

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    End point title
    		 Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil
    End point description
    Time to Reach Maximum Observed Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil
    End point type
    Secondary
    End point timeframe
    PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: hour (hr)
    median (full range (min-max))
        PF-05212384 (n=3,4,2,5,3)
    0.5 (0.45 to 0.5)
    0.55 (0.45 to 0.617)
    0.5 (0.5 to 0.5)
    0.5 (0.383 to 0.5)
    0.5 (0.483 to 1.03)
        Irinotecan (n=3,4,1,5,3)
    2.02 (1.98 to 2.02)
    2.04 (2 to 2.15)
    1.95 (1.95 to 1.95)
    2.25 (1.98 to 2.5)
    2 (1.98 to 2.02)
        Fluorouracil (n=3,4,1,4,3)
    0.083 (0.033 to 0.15)
    0.167 (0.167 to 0.233)
    0.083 (0.083 to 0.083)
    0.125 (0.067 to 0.25)
    0.15 (0.15 to 46.2)
    No statistical analyses for this end point

    Secondary: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384, and Irinotecan

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    End point title
    		 Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384, and Irinotecan
    End point description
    Area Under the Curve From Time Zero to Last Quantifiable Concentration of PF-05212384 and Irinotecan
    End point type
    Secondary
    End point timeframe
    PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: ng*hr/mL
    geometric mean (geometric coefficient of variation)
        PF-05212384 (n=3,4,1,5,3)
    11460 ± 22
    9129 ± 33
    30700 ± 99999
    13570 ± 40
    14760 ± 34
        Irinotecan (n=3,4,1,4,3)
    12510 ± 8
    9164 ± 53
    8050 ± 99999
    10340 ± 15
    11030 ± 28
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan

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    End point title
    		 Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan
    End point description
    Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time of PF-05212384 and Irinotecan
    End point type
    Secondary
    End point timeframe
    PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    1
    5
    3
    Units: ng*hr/mL
    geometric mean (geometric coefficient of variation)
        PF-05212384
    11820 ± 22
    9289 ± 32
    30900 ± 99999
    13830 ± 40
    15270 ± 34
        Irinotecan
    13120 ± 10
    9709 ± 54
    8350 ± 99999
    10900 ± 16
    11560 ± 29
    No statistical analyses for this end point

    Secondary: Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan

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    End point title
    		 Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan
    End point description
    Terminal Elimination Half-Life of PF-05212384 and Irinotecan
    End point type
    Secondary
    End point timeframe
    PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    1
    5
    3
    Units: hour
    arithmetic mean (standard deviation)
        PF-05212384
    33.63 ± 1.3503
    27.9 ± 3.3695
    29.2 ± 99999
    29.18 ± 6.9909
    36.97 ± 1.9035
        Irinotecan
    5.127 ± 0.70692
    5.533 ± 1.1621
    4.97 ± 99999
    5.36 ± 0.40817
    5.107 ± 0.40427
    No statistical analyses for this end point

    Secondary: Number of Subjects Meeting Maximum Post-Baseline QTc Interval Values

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    End point title
    		 Number of Subjects Meeting Maximum Post-Baseline QTc Interval Values
    End point description
    Criteria for corrected QT interval using Fridericia's formula (QTcF) meeting potential clinical concern included: an absolute value >=450 - <480 msec, >=480-<500 msec, >500 msec; an absolute change 30 - <60, >=60 msec.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 1 Day 1, and Cycle 2 Day 2
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    3
    4
    3
    5
    3
    Units: subjects
        QTcF Interval <450 msec
    3
    4
    3
    3
    3
        QTcF Interval 450-480 msec
    0
    0
    0
    2
    0
        QTcF Interval >480-500 msec
    0
    0
    0
    0
    0
        QTcF Interval >500 msec
    0
    0
    0
    0
    0
        QTcF Interval increase =< 30 msec
    2
    3
    3
    4
    3
        QTcF Interval increase >30 to =<60 msec
    1
    1
    0
    1
    0
        QTcF Interval increase >60
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Expression of Gene Sequences or Gene Amplications in Biopsied Tumor Tissue

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    End point title
    		 Number of Subjects with Expression of Gene Sequences or Gene Amplications in Biopsied Tumor Tissue
    End point description
    Biomarker evaluation were to be performed on fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity.
    End point type
    Secondary
    End point timeframe
    Baseline and Cycle 2 Day 17
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    0 [8]
    0 [9]
    0 [10]
    0 [11]
    0 [12]
    Units: subjects
    Notes
    [8] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    [9] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    [10] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    [11] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    [12] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    No statistical analyses for this end point

    Secondary: Number of Subjects with Gene and/or Protein Expression Biomarkers Relating to the PI3K and/or mTOR Pathway Activation in Biopsied Tumor Tissue

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    End point title
    		 Number of Subjects with Gene and/or Protein Expression Biomarkers Relating to the PI3K and/or mTOR Pathway Activation in Biopsied Tumor Tissue
    End point description
    Biomarker evaluation were to be performed on fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity.
    End point type
    Secondary
    End point timeframe
    Baseline and Cycle 2 Day 17
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    0 [13]
    0 [14]
    0 [15]
    0 [16]
    0 [17]
    Units: subjects
    Notes
    [13] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    [14] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    [15] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    [16] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    [17] - Not summarized. Paired fresh tumor biopsies were only done in 1 subject.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Best Overall Response (Phase 2)

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    End point title
    		 Number of Subjects With Best Overall Response (Phase 2)
    End point description
    Best overall response is defined as the best response recorded from randomization (or first dose for patients in the Phase 1B) until disease progression, death, start of new anti-cancer treatment or end of study. The categories for best overall response include: complete response (CR) (complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 millimeters (mm)); partial response (PR) (at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); stable disease (SD) (not qualify for CR, PR or Progression); progressive disease (PD) (20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm); indeterminate (IND) (progression has not been documented).
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 28
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    0 [18]
    0 [19]
    0 [20]
    0 [21]
    0 [22]
    Units: subjects
    Notes
    [18] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [19] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [20] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [21] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [22] - Study was terminated prior to the Phase 2 portion and no data were collected.
    No statistical analyses for this end point

    Secondary: Duration of Response (Phase 2)

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    End point title
    		 Duration of Response (Phase 2)
    End point description
    Duration of response is the time from first documentation of CR or PR to date of first documentation of objective progression or death.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 28
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    0 [23]
    0 [24]
    0 [25]
    0 [26]
    0 [27]
    Units: weeks
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [23] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [24] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [25] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [26] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [27] - Study was terminated prior to the Phase 2 portion and no data were collected.
    No statistical analyses for this end point

    Secondary: Overall Survival (Phase 2)

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    End point title
    		 Overall Survival (Phase 2)
    End point description
    Overall survival is the time from randomization date to date of death due to any cause.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 28
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    0 [28]
    0 [29]
    0 [30]
    0 [31]
    0 [32]
    Units: Weeks
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [28] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [29] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [30] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [31] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [32] - Study was terminated prior to the Phase 2 portion and no data were collected.
    No statistical analyses for this end point

    Secondary: Number of Subjects with Evidence of Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue (Phase 2)

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    End point title
    		 Number of Subjects with Evidence of Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue (Phase 2)
    End point description
    Biomarker evaluation were to be performed on these fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity.
    End point type
    Secondary
    End point timeframe
    Baseline and Cycle 2 Day 17
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    0 [33]
    0 [34]
    0 [35]
    0 [36]
    0 [37]
    Units: subjects
    Notes
    [33] - Phase 2 only and no data were collected for Phase 2.
    [34] - Phase 2 only and no data were collected for Phase 2.
    [35] - Phase 2 only and no data were collected for Phase 2.
    [36] - Phase 2 only and no data were collected for Phase 2.
    [37] - Phase 2 only and no data were collected for Phase 2.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C) (Phase 2)

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    End point title
    		 Change from Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C) (Phase 2)
    End point description
    The FACT-C was to assess health-related quality of life and colorectal cancer (CRC)-related symptoms. It includes a total of 36 items, which are summarized into 6 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), CRC subscale (9 items) which addresses a subset of CRC concerns such as diarrhea.
    End point type
    Secondary
    End point timeframe
    Day 1 of each cycle
    End point values
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Number of subjects analysed
    0 [38]
    0 [39]
    0 [40]
    0 [41]
    0 [42]
    Units: units on a scale
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    ±
    ±
    Notes
    [38] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [39] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [40] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [41] - Study was terminated prior to the Phase 2 portion and no data were collected.
    [42] - Study was terminated prior to the Phase 2 portion and no data were collected.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline to end of treatment
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
    Reporting group description
    		 Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
    Reporting group description
    		 Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
    Reporting group description
    		 Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
    Reporting group description
    		 Participants received intravenous (IV) infusion of PF-05212384 130 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Reporting group title
    PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Reporting group description
    		 Participants received intravenous (IV) infusion of PF-05212384 150 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

    Serious adverse events
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    2 / 3 (66.67%)
    2 / 5 (40.00%)
    3 / 3 (100.00%)
         number of deaths (all causes)
    0
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Anal fistula
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Periorbital infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3 PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    5 / 5 (100.00%)
    3 / 3 (100.00%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Flushing
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    5
    0
    Chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Early satiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Fatigue
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    2 / 5 (40.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    8
    11
    5
    3
    Mucosal inflammation
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    2
    1
    3
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    2
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    2
    0
    0
    Hiccups
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    4
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Sinus disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Throat irritation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Derailment
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    2
    Insomnia
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    2
    0
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    2
    0
    0
    1
    Blood albumin decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 4 (100.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    0
    8
    3
    0
    3
    Platelet count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    1 / 3 (33.33%)
         occurrences all number
    111
    0
    0
    2
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Wound dehiscence
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Disturbance in attention
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    Head discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    5
    1
    3
    1
    Lethargy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Eye disorders
    Eye disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    Vision blurred
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    1
    3
    Cheilitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    1 / 5 (20.00%)
    2 / 3 (66.67%)
         occurrences all number
    0
    1
    2
    1
    2
    Diarrhoea
         subjects affected / exposed
    1 / 3 (33.33%)
    3 / 4 (75.00%)
    3 / 3 (100.00%)
    3 / 5 (60.00%)
    3 / 3 (100.00%)
         occurrences all number
    1
    4
    10
    3
    5
    Dry mouth
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Lip disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Lip swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    3 / 5 (60.00%)
    3 / 3 (100.00%)
         occurrences all number
    2
    4
    4
    3
    5
    Oral dysaesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Oral pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Paraesthesia oral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Proctalgia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    3 / 5 (60.00%)
    2 / 3 (66.67%)
         occurrences all number
    1
    3
    3
    10
    2
    Tongue coated
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    2 / 3 (66.67%)
         occurrences all number
    2
    2
    0
    2
    4
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    2 / 3 (66.67%)
         occurrences all number
    1
    2
    1
    1
    2
    Dry skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    2
    Rash
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    1
    1
    0
    Rash generalised
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Rash papular
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Renal failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Bone pain
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 4 (75.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Musculoskeletal disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Infections and infestations
    Candida infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Herpes zoster
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Periorbital infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    3 / 5 (60.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    0
    4
    2
    Dehydration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    0
    2
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2013
    To incorporate starting dose infromation for the Phase 1b and LIC 5-FU colus infusion and adjust the top dose for the 5-FU continuous infusion in the FOLFIRI regimen.
    20 Feb 2014
    This amendment incorporates all revisions to date, including amendments made at the request of country health authorities, instituional review boards/external review boards.

    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.
    As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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