Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Efficacy and Safety of Farletuzumab (MORAb-003) in Combination with Carboplatin plus Paclitaxel or Carboplatin plus Pegylated Liposomal Doxorubicin (PLD) in Subjects with Low CA125 Platinum-Sensitive Ovarian Cancer

    Summary
    EudraCT number
    		 2014-003812-36
    Trial protocol
    		 BE   DE   GB   ES   IT  
    Global end of trial date
    13 Aug 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Aug 2021
    First version publication date
    25 Aug 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MORAb-003-011
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02289950
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Eisai Ltd.
    Sponsor organisation address
    European Knowledge Centre, Mosquito Way, Hatfield, United Kingdom, AL10 9SN
    Public contact
    Eisai Medical Information, Eisai Inc., 1 888-274-2378, esi_oncmedinfo@eisai.com
    Scientific contact
    Eisai Medical Information, Eisai Inc., 1 888-274-2378, esi_oncmedinfo@eisai.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
    13 Aug 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Aug 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to demonstrate that farletuzumab has superior efficacy compared with placebo in improving Progression-free survival (PFS), as determined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, when added to the standard chemotherapy regimens of carboplatin plus paclitaxel or carboplatin plus PLD, in subjects with platinum-sensitive ovarian cancer in first relapse who have a cancer antigen 125 (CA125) greater than or equal to (>=) 3 x upper limit of normal (ULN) (105 units per milliliter [U/mL]) at study entry.
    Protection of trial subjects
    This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2013) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Mar 2015
    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
    Belgium: 21
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Italy: 35
    Country: Number of subjects enrolled
    Japan: 22
    Country: Number of subjects enrolled
    Spain: 33
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 92
    Worldwide total number of subjects
    214
    EEA total number of subjects
    96
    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)
    117
    From 65 to 84 years
    95
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects took part in the study at 60 investigative sites in the United states, Belgium, Germany, Italy, Spain, United Kingdom and Japan from 19 March 2015 to 13 August 2020.

    Pre-assignment
    Screening details
    		 A total of 332 subjects were screened, of which 118 were screen failures and 214 were randomized out of which 211 were treated.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD
    Arm description
    		 Subjects received either carboplatin (area under the concentration-time curve [AUC] 5) plus paclitaxel 175 milligrams per square meter (mg/m^2) intravenously (IV) every 3 weeks or carboplatin (AUC 5) plus PLD 30 mg/m^2 IV every 4 weeks in combination with farletuzumab loading dose of 10 milligram per kilogram (mg/kg) for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 8 cycles at the investigator’s discretion. Subjects who completed combination treatment phase and subjects who experienced intolerable toxicity to chemotherapy in combination treatment phase continued to receive maintenance treatment with farletuzumab 5 mg/kg every week alone up to maximum of 64 cycles or until disease progression was confirmed by radiographic assessment, or subject discontinued treatment for any other reason.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Farletuzumab
    Investigational medicinal product code
    Other name
    MORAb-003
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Farletuzumab loading dose of 10 mg/kg for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 64 cycles or disease progression.

    Arm title
    		 Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Arm description
    		 Subjects received either carboplatin (AUC 5) plus paclitaxel 175 mg/m^2 IV every 3 weeks or carboplatin (AUC 5) plus PLD 30 mg/m^2 IV every 4 weeks in combination with placebo loading dose of 10 mg/kg for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 8 cycles at the investigator’s discretion. Subjects who completed combination treatment phase and subjects who experienced intolerable toxicity to chemotherapy in combination treatment phase continued to receive maintenance treatment with placebo 5 mg/kg every week alone up to maximum of 64 cycles or until disease progression was confirmed by radiographic assessment, or subject discontinued treatment for any other reason.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo loading dose of 10 mg/kg for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 64 cycles or disease progression.

    Number of subjects in period 1
    		Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Started
    142
    72
    Completed
    0
    0
    Not completed
    142
    72
         Test article held for greater than 28 days
    -
    1
         Physician decision
    9
    3
         Consent withdrawn by subject
    1
    3
         Subject discontinued therapy
    9
    2
         Adverse event, non-fatal
    11
    3
         Other
    5
    2
         Not Treated
    2
    1
         Death
    1
    1
         Progressive disease by RECIST 1.1
    99
    52
         Lost to follow-up
    1
    -
         Progressive disease by Clinical Assessment
    4
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD
    Reporting group description
    		 Subjects received either carboplatin (area under the concentration-time curve [AUC] 5) plus paclitaxel 175 milligrams per square meter (mg/m^2) intravenously (IV) every 3 weeks or carboplatin (AUC 5) plus PLD 30 mg/m^2 IV every 4 weeks in combination with farletuzumab loading dose of 10 milligram per kilogram (mg/kg) for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 8 cycles at the investigator’s discretion. Subjects who completed combination treatment phase and subjects who experienced intolerable toxicity to chemotherapy in combination treatment phase continued to receive maintenance treatment with farletuzumab 5 mg/kg every week alone up to maximum of 64 cycles or until disease progression was confirmed by radiographic assessment, or subject discontinued treatment for any other reason.

    Reporting group title
    Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Reporting group description
    		 Subjects received either carboplatin (AUC 5) plus paclitaxel 175 mg/m^2 IV every 3 weeks or carboplatin (AUC 5) plus PLD 30 mg/m^2 IV every 4 weeks in combination with placebo loading dose of 10 mg/kg for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 8 cycles at the investigator’s discretion. Subjects who completed combination treatment phase and subjects who experienced intolerable toxicity to chemotherapy in combination treatment phase continued to receive maintenance treatment with placebo 5 mg/kg every week alone up to maximum of 64 cycles or until disease progression was confirmed by radiographic assessment, or subject discontinued treatment for any other reason.

    Reporting group values
    		 Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD Total
    Number of subjects
    		 142 72 214
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.0 ( 10.74 ) 62.9 ( 10.50 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 141 72 213
        Unknown
    		 1 0 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 12 3 15
        Not Hispanic or Latino
    		 126 68 194
        Unknown or Not Reported
    		 4 1 5
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 14 8 22
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 8 2 10
        White
    		 117 62 179
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 3 0 3

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD
    Reporting group description
    		 Subjects received either carboplatin (area under the concentration-time curve [AUC] 5) plus paclitaxel 175 milligrams per square meter (mg/m^2) intravenously (IV) every 3 weeks or carboplatin (AUC 5) plus PLD 30 mg/m^2 IV every 4 weeks in combination with farletuzumab loading dose of 10 milligram per kilogram (mg/kg) for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 8 cycles at the investigator’s discretion. Subjects who completed combination treatment phase and subjects who experienced intolerable toxicity to chemotherapy in combination treatment phase continued to receive maintenance treatment with farletuzumab 5 mg/kg every week alone up to maximum of 64 cycles or until disease progression was confirmed by radiographic assessment, or subject discontinued treatment for any other reason.

    Reporting group title
    Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Reporting group description
    		 Subjects received either carboplatin (AUC 5) plus paclitaxel 175 mg/m^2 IV every 3 weeks or carboplatin (AUC 5) plus PLD 30 mg/m^2 IV every 4 weeks in combination with placebo loading dose of 10 mg/kg for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 8 cycles at the investigator’s discretion. Subjects who completed combination treatment phase and subjects who experienced intolerable toxicity to chemotherapy in combination treatment phase continued to receive maintenance treatment with placebo 5 mg/kg every week alone up to maximum of 64 cycles or until disease progression was confirmed by radiographic assessment, or subject discontinued treatment for any other reason.

    Primary: Progression Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS) [1]
    End point description
    PFS was defined as the time (in months) from the date of randomization of a subject to the date of first observation of progression or date of death, whatever the cause. PFS was assessed based on the investigators’ assessments utilizing Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Disease progression (PD) was defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method. The intent to treat (ITT) Population (Full Analysis Set) included all randomized subjects according to the assigned treatment by interactive response technology (IRT) system.
    End point type
    Primary
    End point timeframe
    From the date of randomization to the date of first documentation of PD, or date of death, whichever occurs first up to approximately 5 years 5 months
    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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Number of subjects analysed
    142
    72
    Units: Months
        median (confidence interval 95%)
    11.73 (10.22 to 13.60)
    10.78 (9.49 to 13.17)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from the date of randomization until the date of death. Subjects were censored at the date of last known to be alive. OS was analyzed using Kaplan-Meier method. The ITT Population (Full Analysis Set) included all randomized subjects according to the assigned treatment by IRT system. Here '99999' means that the upper limit of 95% confidence interval (CI) was not estimable due to insufficient number of events.
    End point type
    Secondary
    End point timeframe
    From the date of randomization until the date of death (up to approximately 5 years 5 months)
    End point values
    		 Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Number of subjects analysed
    142
    72
    Units: Months
        median (confidence interval 95%)
    43.07 (37.13 to 99999)
    42.45 (37.85 to 99999)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Best Overall Response (BOR)

    		 Close Top of page
    End point title
    		 Number of Subjects With Best Overall Response (BOR)
    End point description
    BOR was defined as the best response of complete response (CR) or partial response (PR) or stable disease (SD) for >=6 months recorded from the start of the treatment until PD or death, whichever occurred first based on investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Tumor Response Evaluable Analysis Set was used.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug (Baseline) up to approximately 5 years 5 months
    End point values
    		 Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Number of subjects analysed
    138
    68
    Units: Subjects
        Complete Response
    24
    15
        Partial Response
    72
    35
        Stable Disease
    36
    17
    No statistical analyses for this end point

    Secondary: Time to Tumor Response (TTR)

    		 Close Top of page
    End point title
    		 Time to Tumor Response (TTR)
    End point description
    TTR was defined as the time (in months) from the date of randomization to the date of first observation of response (PR or CR) (whichever status was recorded first). TTR was assessed based on investigator assessment utilizing RECIST 1.1. CR: disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. Tumor Response Evaluable Analysis Set included all randomized subjects who received at least 1 dose of study drug and who had a baseline and at least 1 on treatment tumor assessment performed. Here "number of subjects analyzed" signifies subjects who had CR or PR.
    End point type
    Secondary
    End point timeframe
    From the date of randomization until date of first observation of response (CR or PR) up to approximately 5 years 5 months
    End point values
    		 Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Number of subjects analysed
    96
    50
    Units: months
        median (confidence interval 95%)
    2.69 (1.74 to 2.83)
    2.53 (1.48 to 2.69)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

    		 Close Top of page
    End point title
    		 Duration of Response (DOR)
    End point description
    DOR was defined as the time (in months) from the date of first observation of response (PR or CR) to the date of the first observation of progression based on the investigator’s assessment utilizing RECIST 1.1, or date of death, whatever the cause. CR: disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Tumor Response Evaluable Analysis Set was used. Here "number of subjects analyzed" signifies subjects who had CR or PR.
    End point type
    Secondary
    End point timeframe
    From date of the first observation of CR or PR until the date of first observation of progression or date of death up to approximately 5 years 5 months
    End point values
    		 Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Number of subjects analysed
    96
    50
    Units: months
        median (confidence interval 95%)
    10.12 (8.54 to 11.47)
    8.51 (6.31 to 10.97)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving Each Second Platinum-Free Interval Stratified by First Platinum-Free Interval

    		 Close Top of page
    End point title
    		 Percentage of Subjects Achieving Each Second Platinum-Free Interval Stratified by First Platinum-Free Interval
    End point description
    Percentage of Subjects achieving each second platinum-free interval (SPFI) (<6 months, 6-12 months, greater than [>] 12-36 months, and >36 months) stratified by first platinum-free interval (FPFI) (6 to 12 months and >12 to 36 months) was reported. First platinum-free interval was defined as the date of completion of previous platinum-based chemotherapy until the date of first relapse (that is, first observation of progression). The date of first relapse was the progression date. Second platinum-free interval was defined as the date of completion of platinum-based chemotherapy (last dosing date) during the study until the date of progression or death (or censoring, if applicable).The ITT Population (Full Analysis Set) included all randomized subjects according to the assigned treatment by IRT system.
    End point type
    Secondary
    End point timeframe
    From the date of randomization to the date of first relapse (or first observation of progression/death) up to approximately 5 year 5 months
    End point values
    		 Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Number of subjects analysed
    142
    72
    Units: Percentage of subjects
    number (confidence interval 95%)
        SPFI(<6 months): FPFI(6 to 12 months)
    71.2 (57.92 to 82.42)
    63.3 (43.86 to 80.07)
        SPFI (6-12 months): FPFI (6 to 12 months)
    6.8 (1.88 to 16.46)
    23.3 (9.93 to 42.28)
        SPFI(>12-36 months): FPFI(6 to 12 months)
    16.9 (8.44 to 28.97)
    10.0 (2.11 to 26.53)
        SPFI(>36 months): FPFI (6 to 12 months)
    0.0 (0.00 to 6.60)
    0.0 (0.00 to 11.57)
        SPFI(<6 months): FPFI(>12 to 36 months)
    42.2 (31.40 to 53.51)
    52.4 (36.42 to 68.00)
        SPFI(6-12 months): FPFI (>12 to 36 months)
    33.7 (23.72 to 44.95)
    28.6 (15.72 to 44.58)
        SPFI(>12-36 months): FPFI (>12 to 36 months)
    20.5 (12.41 to 30.76)
    16.7 (6.97 to 31.36)
        SPFI(>36 months): FPFI(>12 to 36 months)
    0.0 (0.00 to 4.35)
    0.0 (0.00 to 8.41)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From date of first dose up to 30 days after the last dose of study treatment (up to approximately 5 years 5 months)
    Adverse event reporting additional description
    Deaths that happened anytime during the study (including those during the treatment and after treatment discontinuation) are reported in this section.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD
    Reporting group description
    		 Subjects received either carboplatin (AUC 5) plus paclitaxel 175 mg/m^2 IV every 3 weeks or carboplatin (AUC 5) plus PLD 30 mg/m^2 IV every 4 weeks in combination with placebo loading dose of 10 mg/kg for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 8 cycles at the investigator’s discretion. Subjects who completed combination treatment phase and subjects who experienced intolerable toxicity to chemotherapy in combination treatment phase continued to receive maintenance treatment with placebo 5 mg/kg every week alone up to maximum of 64 cycles or until disease progression was confirmed by radiographic assessment, or subject discontinued treatment for any other reason.

    Reporting group title
    Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD
    Reporting group description
    		 Subjects received either carboplatin (area under the concentration-time curve [AUC] 5) plus paclitaxel 175 milligrams per square meter (mg/m^2) intravenously (IV) every 3 weeks or carboplatin (AUC 5) plus PLD 30 mg/m^2 IV every 4 weeks in combination with farletuzumab loading dose of 10 milligram per kilogram (mg/kg) for the first 2 weeks, followed by 5 mg/kg every week thereafter administered up to maximum of 8 cycles at the investigator’s discretion. Subjects who completed combination treatment phase and Subjects who experienced intolerable toxicity to chemotherapy in combination treatment phase continued to receive maintenance treatment with farletuzumab 5 mg/kg every week alone up to maximum of 64 cycles or until disease progression was confirmed by radiographic assessment, or subject discontinued treatment for any other reason.

    Serious adverse events
    		 Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD
    Total subjects affected by serious adverse events
         subjects affected / exposed
    18 / 70 (25.71%)
    42 / 141 (29.79%)
         number of deaths (all causes)
    2
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to meninges
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    2 / 70 (2.86%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 141 (1.42%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Restrictive pulmonary disease
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Carbon monoxide diffusing capacity decreased
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 141 (1.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Heat illness
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 141 (1.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Depressed level of consciousness
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 70 (1.43%)
    2 / 141 (1.42%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 70 (1.43%)
    6 / 141 (4.26%)
         occurrences causally related to treatment / all
    0 / 1
    5 / 9
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Neutropenia
         subjects affected / exposed
    2 / 70 (2.86%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 141 (1.42%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 70 (2.86%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 70 (2.86%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 70 (0.00%)
    3 / 141 (2.13%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 70 (1.43%)
    5 / 141 (3.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 70 (1.43%)
    3 / 141 (2.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 70 (1.43%)
    7 / 141 (4.96%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Strangulated umbilical hernia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 70 (2.86%)
    2 / 141 (1.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Petechiae
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 141 (1.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 141 (1.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Tracheitis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 141 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 141 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo + Carboplatin/Paclitaxel or Carboplatin/PLD Farletuzumab 5 mg/kg+Carboplatin/Paclitaxel or Carboplatin/PLD
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    70 / 70 (100.00%)
    140 / 141 (99.29%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    9 / 70 (12.86%)
    4 / 141 (2.84%)
         occurrences all number
    17
    4
    Hypertension
         subjects affected / exposed
    5 / 70 (7.14%)
    7 / 141 (4.96%)
         occurrences all number
    14
    10
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    14 / 70 (20.00%)
    33 / 141 (23.40%)
         occurrences all number
    42
    90
    Chills
         subjects affected / exposed
    5 / 70 (7.14%)
    6 / 141 (4.26%)
         occurrences all number
    5
    9
    Influenza like illness
         subjects affected / exposed
    4 / 70 (5.71%)
    8 / 141 (5.67%)
         occurrences all number
    5
    10
    Fatigue
         subjects affected / exposed
    35 / 70 (50.00%)
    69 / 141 (48.94%)
         occurrences all number
    55
    112
    Malaise
         subjects affected / exposed
    9 / 70 (12.86%)
    9 / 141 (6.38%)
         occurrences all number
    11
    14
    Oedema peripheral
         subjects affected / exposed
    12 / 70 (17.14%)
    16 / 141 (11.35%)
         occurrences all number
    19
    21
    Peripheral swelling
         subjects affected / exposed
    4 / 70 (5.71%)
    4 / 141 (2.84%)
         occurrences all number
    4
    4
    Pyrexia
         subjects affected / exposed
    11 / 70 (15.71%)
    23 / 141 (16.31%)
         occurrences all number
    16
    37
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    5 / 70 (7.14%)
    4 / 141 (2.84%)
         occurrences all number
    6
    4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    16 / 70 (22.86%)
    43 / 141 (30.50%)
         occurrences all number
    25
    65
    Dyspnoea
         subjects affected / exposed
    9 / 70 (12.86%)
    31 / 141 (21.99%)
         occurrences all number
    13
    47
    Epistaxis
         subjects affected / exposed
    5 / 70 (7.14%)
    7 / 141 (4.96%)
         occurrences all number
    7
    10
    Nasal congestion
         subjects affected / exposed
    2 / 70 (2.86%)
    10 / 141 (7.09%)
         occurrences all number
    3
    11
    Oropharyngeal pain
         subjects affected / exposed
    7 / 70 (10.00%)
    16 / 141 (11.35%)
         occurrences all number
    10
    18
    Psychiatric disorders
    Depression
         subjects affected / exposed
    6 / 70 (8.57%)
    6 / 141 (4.26%)
         occurrences all number
    16
    6
    Anxiety
         subjects affected / exposed
    5 / 70 (7.14%)
    15 / 141 (10.64%)
         occurrences all number
    5
    18
    Insomnia
         subjects affected / exposed
    8 / 70 (11.43%)
    15 / 141 (10.64%)
         occurrences all number
    11
    17
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 70 (5.71%)
    7 / 141 (4.96%)
         occurrences all number
    4
    10
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 70 (5.71%)
    10 / 141 (7.09%)
         occurrences all number
    4
    16
    Neutrophil count decreased
         subjects affected / exposed
    18 / 70 (25.71%)
    44 / 141 (31.21%)
         occurrences all number
    90
    165
    Platelet count decreased
         subjects affected / exposed
    11 / 70 (15.71%)
    27 / 141 (19.15%)
         occurrences all number
    46
    83
    White blood cell count decreased
         subjects affected / exposed
    14 / 70 (20.00%)
    34 / 141 (24.11%)
         occurrences all number
    68
    127
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    13 / 70 (18.57%)
    22 / 141 (15.60%)
         occurrences all number
    19
    40
    Dysgeusia
         subjects affected / exposed
    12 / 70 (17.14%)
    15 / 141 (10.64%)
         occurrences all number
    17
    22
    Headache
         subjects affected / exposed
    27 / 70 (38.57%)
    49 / 141 (34.75%)
         occurrences all number
    61
    77
    Paraesthesia
         subjects affected / exposed
    8 / 70 (11.43%)
    11 / 141 (7.80%)
         occurrences all number
    13
    14
    Peripheral sensory neuropathy
         subjects affected / exposed
    14 / 70 (20.00%)
    23 / 141 (16.31%)
         occurrences all number
    21
    31
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    36 / 70 (51.43%)
    76 / 141 (53.90%)
         occurrences all number
    121
    208
    Leukopenia
         subjects affected / exposed
    7 / 70 (10.00%)
    21 / 141 (14.89%)
         occurrences all number
    20
    74
    Neutropenia
         subjects affected / exposed
    24 / 70 (34.29%)
    55 / 141 (39.01%)
         occurrences all number
    82
    225
    Thrombocytopenia
         subjects affected / exposed
    19 / 70 (27.14%)
    42 / 141 (29.79%)
         occurrences all number
    86
    109
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    5 / 70 (7.14%)
    3 / 141 (2.13%)
         occurrences all number
    5
    3
    Vertigo
         subjects affected / exposed
    6 / 70 (8.57%)
    8 / 141 (5.67%)
         occurrences all number
    9
    8
    Eye disorders
    Vision blurred
         subjects affected / exposed
    5 / 70 (7.14%)
    7 / 141 (4.96%)
         occurrences all number
    5
    7
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    9 / 70 (12.86%)
    9 / 141 (6.38%)
         occurrences all number
    11
    14
    Abdominal distension
         subjects affected / exposed
    4 / 70 (5.71%)
    9 / 141 (6.38%)
         occurrences all number
    5
    12
    Abdominal pain upper
         subjects affected / exposed
    12 / 70 (17.14%)
    17 / 141 (12.06%)
         occurrences all number
    17
    19
    Abdominal pain
         subjects affected / exposed
    22 / 70 (31.43%)
    39 / 141 (27.66%)
         occurrences all number
    34
    65
    Constipation
         subjects affected / exposed
    31 / 70 (44.29%)
    58 / 141 (41.13%)
         occurrences all number
    53
    93
    Diarrhoea
         subjects affected / exposed
    27 / 70 (38.57%)
    48 / 141 (34.04%)
         occurrences all number
    63
    83
    Dry mouth
         subjects affected / exposed
    6 / 70 (8.57%)
    9 / 141 (6.38%)
         occurrences all number
    8
    9
    Dyspepsia
         subjects affected / exposed
    10 / 70 (14.29%)
    12 / 141 (8.51%)
         occurrences all number
    14
    15
    Nausea
         subjects affected / exposed
    45 / 70 (64.29%)
    95 / 141 (67.38%)
         occurrences all number
    110
    187
    Gastrooesophageal reflux disease
         subjects affected / exposed
    5 / 70 (7.14%)
    12 / 141 (8.51%)
         occurrences all number
    6
    18
    Stomatitis
         subjects affected / exposed
    24 / 70 (34.29%)
    44 / 141 (31.21%)
         occurrences all number
    51
    66
    Vomiting
         subjects affected / exposed
    27 / 70 (38.57%)
    43 / 141 (30.50%)
         occurrences all number
    56
    74
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    15 / 70 (21.43%)
    26 / 141 (18.44%)
         occurrences all number
    19
    29
    Blister
         subjects affected / exposed
    4 / 70 (5.71%)
    0 / 141 (0.00%)
         occurrences all number
    5
    0
    Erythema
         subjects affected / exposed
    4 / 70 (5.71%)
    9 / 141 (6.38%)
         occurrences all number
    4
    9
    Dry skin
         subjects affected / exposed
    9 / 70 (12.86%)
    4 / 141 (2.84%)
         occurrences all number
    10
    5
    Nail discolouration
         subjects affected / exposed
    4 / 70 (5.71%)
    4 / 141 (2.84%)
         occurrences all number
    4
    4
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    9 / 70 (12.86%)
    11 / 141 (7.80%)
         occurrences all number
    13
    13
    Pruritus
         subjects affected / exposed
    9 / 70 (12.86%)
    15 / 141 (10.64%)
         occurrences all number
    14
    17
    Rash
         subjects affected / exposed
    13 / 70 (18.57%)
    24 / 141 (17.02%)
         occurrences all number
    15
    38
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    4 / 70 (5.71%)
    11 / 141 (7.80%)
         occurrences all number
    5
    16
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    15 / 70 (21.43%)
    36 / 141 (25.53%)
         occurrences all number
    27
    52
    Arthritis
         subjects affected / exposed
    5 / 70 (7.14%)
    1 / 141 (0.71%)
         occurrences all number
    6
    1
    Back pain
         subjects affected / exposed
    18 / 70 (25.71%)
    18 / 141 (12.77%)
         occurrences all number
    24
    24
    Bone pain
         subjects affected / exposed
    4 / 70 (5.71%)
    6 / 141 (4.26%)
         occurrences all number
    7
    10
    Flank pain
         subjects affected / exposed
    4 / 70 (5.71%)
    3 / 141 (2.13%)
         occurrences all number
    4
    3
    Muscle spasms
         subjects affected / exposed
    11 / 70 (15.71%)
    8 / 141 (5.67%)
         occurrences all number
    17
    9
    Muscular weakness
         subjects affected / exposed
    4 / 70 (5.71%)
    3 / 141 (2.13%)
         occurrences all number
    4
    5
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 70 (1.43%)
    9 / 141 (6.38%)
         occurrences all number
    1
    11
    Musculoskeletal pain
         subjects affected / exposed
    6 / 70 (8.57%)
    13 / 141 (9.22%)
         occurrences all number
    6
    15
    Myalgia
         subjects affected / exposed
    7 / 70 (10.00%)
    15 / 141 (10.64%)
         occurrences all number
    13
    19
    Neck pain
         subjects affected / exposed
    4 / 70 (5.71%)
    6 / 141 (4.26%)
         occurrences all number
    6
    7
    Pain in extremity
         subjects affected / exposed
    12 / 70 (17.14%)
    17 / 141 (12.06%)
         occurrences all number
    18
    22
    Infections and infestations
    Cystitis
         subjects affected / exposed
    4 / 70 (5.71%)
    6 / 141 (4.26%)
         occurrences all number
    5
    9
    Influenza
         subjects affected / exposed
    7 / 70 (10.00%)
    9 / 141 (6.38%)
         occurrences all number
    9
    12
    Nasopharyngitis
         subjects affected / exposed
    14 / 70 (20.00%)
    22 / 141 (15.60%)
         occurrences all number
    26
    34
    Sinusitis
         subjects affected / exposed
    8 / 70 (11.43%)
    10 / 141 (7.09%)
         occurrences all number
    11
    11
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 70 (8.57%)
    23 / 141 (16.31%)
         occurrences all number
    8
    29
    Urinary tract infection
         subjects affected / exposed
    16 / 70 (22.86%)
    18 / 141 (12.77%)
         occurrences all number
    32
    24
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    18 / 70 (25.71%)
    28 / 141 (19.86%)
         occurrences all number
    32
    43
    Dehydration
         subjects affected / exposed
    7 / 70 (10.00%)
    13 / 141 (9.22%)
         occurrences all number
    8
    21
    Hyperglycaemia
         subjects affected / exposed
    6 / 70 (8.57%)
    7 / 141 (4.96%)
         occurrences all number
    6
    18
    Hypertriglyceridaemia
         subjects affected / exposed
    4 / 70 (5.71%)
    7 / 141 (4.96%)
         occurrences all number
    4
    12
    Hypokalaemia
         subjects affected / exposed
    4 / 70 (5.71%)
    23 / 141 (16.31%)
         occurrences all number
    9
    49
    Hypomagnesaemia
         subjects affected / exposed
    7 / 70 (10.00%)
    21 / 141 (14.89%)
         occurrences all number
    11
    33

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Feb 2015
    The protocol was amended to add method of randomization, updated Inclusion Criteria and exclusion criteria, clarified stopping rules for the study, added urine pregnancy testing (to be conducted locally), specified that the censoring and handling rules on missing values will be detailed in the statistical analysis plan, as well as potential sensitivity analyses with regard to missing values and updated quantities of blood to be drawn for bioanalytical sampling to more closely align with central laboratory blood sample handling practices, statement instructing sites to send images to central imaging laboratory for rapid reads in the case of suspected disease progression was removed and removal of reference to subject initials on the Investigational Product accountability log as only subject number will be captured.
    18 Dec 2017
    The protocol was amended to remove the 1:1 target stratification ratio and the associated minimum enrollment of 105 subjects per stratum and the description of the required number PFS events, sample size considerations were no longer based on the effect of farletuzumab on PFS in each of the 2 chemotherapy regimens, changed assumption for median PFS to 11 months in the control arm, changed assumption for median OS to 32 months, removed the description of the secondary efficacy analyses to be conducted in both strata, added that the primary and secondary analyses (PFS, OS, ORR, DR) in each strata were to be considered as exploratory analyses, revised inclusion and exclusion criteria and added that the alpha allocation between the interim and final OS analyses will be determined based on the Lan-DeMets spending function with O’Brien-Fleming boundary.
    06 Nov 2018
    The protocol was amended to replace “Morphotek” with “Eisai” to update study ownership.

    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
    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.

    European Medicines Agency © 1995-Fri May 03 14:52:36 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA