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   43865   clinical trials with a EudraCT protocol, of which   7286   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 multicenter, open label, controlled and non-comparative phase II study of anti–PDL1 ATEZOLIZUMAB (MPDL3280A) or chemotherapy as second-line therapy in patients with small cell lung cancer (SCLC)

    Summary
    EudraCT number
    		 2016-003795-49
    Trial protocol
    		 FR  
    Global end of trial date
    01 Dec 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Feb 2023
    First version publication date
    01 Feb 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IFCT-1603
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03059667
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    IFCT
    Sponsor organisation address
    10 rue de la Grange-Batelière, Paris, France, 75009
    Public contact
    Contact, IFCT, 0033 0156811046, contact@ifct.fr
    Scientific contact
    Contact, IFCT, 0033 0156811046, contact@ifct.fr
    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
    30 Jun 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Dec 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the activity of anti-PDL1 antibody ATEZOLIZUMAB (MPDL3280A) in second line after progression following platinum – etoposide regimen Phase II component of the study
    Protection of trial subjects
    Algorithms for management of adverse events were provided in the protocol.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Feb 2017
    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
    France: 73
    Worldwide total number of subjects
    73
    EEA total number of subjects
    73
    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)
    37
    From 65 to 84 years
    34
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 73 patients from 24 centres were randomised in the study from March to December 2017; 49 in the experimental anti-PD-L1 arm and 24 in the control chemotherapy arm. 48 out of the 49 patients in the anti-PD-L1 arm received the study treatment atezolizumab. 24 out of the 24 patients in the chemotherapy arm received chemotherapy.

    Pre-assignment
    Screening details
    		 Eligible patients: histologically confirmed SCLC with relapse after first-line chemotherapy (platinum compound and etoposide). Main eligibility criteria: proven progressive disease other than brain metastasis or carcinomatous meningitis, performance status 0–2, measurable disease according to RECIST v1.1 and no active brain metastases.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Anti-PD-L1 atezolizumab
    Arm description
    		 Patients in the anti-PD-L1 arm received the treatment atezolizumab 1200 mg IV, every three weeks until progression or inacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    In vitro use
    Dosage and administration details
    Anti PDL1 atezolizumab (MPDL3280A) at a fixed dose of 1200 mg IV every three weeks until progression or inacceptable toxicity.

    Arm title
    		 Conventional chemotherapy
    Arm description
    		 Patients in the control arm received up to 6 cycles of conventional chemotherapy i.e. second line oral or IV topotecan (oral 2.3 mg/m² or IV 1.5 mg/m² day 1-5 recommended), or re-induction of carboplatin-etoposide doublet (investigator choice based on center policy).
    Arm type
    		 Control

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Anti-PD-L1 atezolizumab Conventional chemotherapy
    Started
    49
    24
    Completed
    3
    11
    Not completed
    46
    13
         Consent withdrawn by subject
    -
    1
         Adverse event, non-fatal
    -
    2
         Did not start treatment
    1
    -
         Death
    6
    -
         Lost to follow-up
    -
    1
         Lack of efficacy
    39
    9

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Anti-PD-L1 atezolizumab
    Reporting group description
    		 Patients in the anti-PD-L1 arm received the treatment atezolizumab 1200 mg IV, every three weeks until progression or inacceptable toxicity.

    Reporting group title
    Conventional chemotherapy
    Reporting group description
    		 Patients in the control arm received up to 6 cycles of conventional chemotherapy i.e. second line oral or IV topotecan (oral 2.3 mg/m² or IV 1.5 mg/m² day 1-5 recommended), or re-induction of carboplatin-etoposide doublet (investigator choice based on center policy).

    Reporting group values
    		 Anti-PD-L1 atezolizumab Conventional chemotherapy Total
    Number of subjects
    		 49 24 73
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 22 15 37
        From 65-84 years
    		 25 9 34
        85 years and over
    		 2 0 2
    Gender categorical
    Units: Subjects
        Female
    		 19 11 30
        Male
    		 30 13 43
    Performance status
    Units: Subjects
        PS 2
    		 8 3 11
        PS 0-1
    		 41 21 62
    Relapse status
    Units: Subjects
        Refractory disease
    		 16 10 26
        Sensitive disease
    		 33 14 47
    Smoker (current or former)
    Units: Subjects
        Yes
    		 47 23 70
        No
    		 2 1 3
    Stage at time of randomisation
    Units: Subjects
        Extensive
    		 39 15 54
        Limited
    		 10 9 19
    Subject analysis sets

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All patients included in the trial.

    Subject analysis set title
    Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All patients who received at least one dose of treatment.

    Subject analysis set title
    Per protocol
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients in the ITT analysis set with no major deviations on inclusion and non-inclusion criteria.

    Subject analysis set title
    ITT Arm Atezolizumab
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients in the ITT analysis set who were randomised to the atezolizumab arm.

    Subject analysis set title
    ITT Arm Chemotherapy
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients in the ITT analysis set who were randomised to the chemotherapy arm.

    Subject analysis set title
    PP Arm Atezolizumab
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients in the PP analysis set who were randomised to the atezolizumab arm.

    Subject analysis set title
    PP Arm Chemotherapy
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients in the PP analysis set who were randomised to the chemotherapy arm.

    Subject analysis set title
    Mutation detected in ctDNA
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients with mutations detected in ctDNA from a blood sample taken at baseline.

    Subject analysis set title
    No mutation detected in ctDNA
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients with no mutations detected in ctDNA from a blood sample taken at baseline.

    Subject analysis sets values
    		 ITT Safety Per protocol ITT Arm Atezolizumab ITT Arm Chemotherapy PP Arm Atezolizumab PP Arm Chemotherapy Mutation detected in ctDNA No mutation detected in ctDNA
    Number of subjects
    73
    72
    63
    49
    24
    43
    20
    49
    19
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units:
        
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    19
    10
        Male
    30
    9
    Performance status
    Units: Subjects
        PS 2
    5
    4
        PS 0-1
    44
    15
    Relapse status
    Units: Subjects
        Refractory disease
    17
    7
        Sensitive disease
    32
    12
    Smoker (current or former)
    Units: Subjects
        Yes
    48
    18
        No
    1
    1
    Stage at time of randomisation
    Units: Subjects
        Extensive
    39
    13
        Limited
    10
    6

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Anti-PD-L1 atezolizumab
    Reporting group description
    		 Patients in the anti-PD-L1 arm received the treatment atezolizumab 1200 mg IV, every three weeks until progression or inacceptable toxicity.

    Reporting group title
    Conventional chemotherapy
    Reporting group description
    		 Patients in the control arm received up to 6 cycles of conventional chemotherapy i.e. second line oral or IV topotecan (oral 2.3 mg/m² or IV 1.5 mg/m² day 1-5 recommended), or re-induction of carboplatin-etoposide doublet (investigator choice based on center policy).

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All patients included in the trial.

    Subject analysis set title
    Safety
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All patients who received at least one dose of treatment.

    Subject analysis set title
    Per protocol
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients in the ITT analysis set with no major deviations on inclusion and non-inclusion criteria.

    Subject analysis set title
    ITT Arm Atezolizumab
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients in the ITT analysis set who were randomised to the atezolizumab arm.

    Subject analysis set title
    ITT Arm Chemotherapy
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Patients in the ITT analysis set who were randomised to the chemotherapy arm.

    Subject analysis set title
    PP Arm Atezolizumab
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients in the PP analysis set who were randomised to the atezolizumab arm.

    Subject analysis set title
    PP Arm Chemotherapy
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Patients in the PP analysis set who were randomised to the chemotherapy arm.

    Subject analysis set title
    Mutation detected in ctDNA
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients with mutations detected in ctDNA from a blood sample taken at baseline.

    Subject analysis set title
    No mutation detected in ctDNA
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients with no mutations detected in ctDNA from a blood sample taken at baseline.

    Primary: Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Objective Response Rate (ORR) [1]
    End point description
    End point type
    Primary
    End point timeframe
    6 weeks after baseline.
    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: Non comparative study.
    End point values
    		 PP Arm Atezolizumab PP Arm Chemotherapy
    Number of subjects analysed
    43
    20
    Units: patient
        Objective Response
    1
    2
        Stable
    8
    11
        Progression
    30
    6
        Not done / Not evaluable
    4
    1
    No statistical analyses for this end point

    Secondary: Quality of life

    		 Close Top of page
    End point title
    		 Quality of life
    End point description
    We analyzed the proportion of patients who reported a decrease by at least 1 point in each symptom recorded by the Lung Cancer Symptom Scale (LCSS).
    End point type
    Secondary
    End point timeframe
    6 weeks after baseline.
    End point values
    		 ITT Arm Atezolizumab ITT Arm Chemotherapy
    Number of subjects analysed
    22
    14
    Units: percentage
    27
    29
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    End point type
    Secondary
    End point timeframe
    Total duration of trial (including follow-up). Cut-off date 30 June 2018.
    End point values
    		 ITT Arm Atezolizumab ITT Arm Chemotherapy PP Arm Atezolizumab PP Arm Chemotherapy Mutation detected in ctDNA No mutation detected in ctDNA
    Number of subjects analysed
    49
    24
    43
    20
    49
    19
    Units: month
        median (confidence interval 95%)
    9.5 (3.2 to 14.4)
    8.7 (4.1 to 12.7)
    11.4 (3.7 to 15.3)
    9.4 (3.8 to 12.7)
    7.6 (3.7 to 12.0)
    13.3 (4.1 to 15.0)
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS)
    End point description
    End point type
    Secondary
    End point timeframe
    Total duration of trial (including follow-up). Cut-off date 30 June 2018.
    End point values
    		 ITT Arm Atezolizumab ITT Arm Chemotherapy PP Arm Atezolizumab PP Arm Chemotherapy Mutation detected in ctDNA No mutation detected in ctDNA
    Number of subjects analysed
    49
    24
    43
    20
    49
    19
    Units: month
        median (confidence interval 95%)
    1.4 (1.2 to 1.5)
    4.3 (1.5 to 5.9)
    1.4 (1.2 to 1.5)
    4.3 (1.5 to 5.9)
    1.5 (1.3 to 1.6)
    2.7 (1.2 to 4.1)
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR)

    		 Close Top of page
    End point title
    		 Disease Control Rate (DCR)
    End point description
    End point type
    Secondary
    End point timeframe
    6 weeks after baseline.
    End point values
    		 ITT Arm Atezolizumab ITT Arm Chemotherapy PP Arm Atezolizumab PP Arm Chemotherapy Mutation detected in ctDNA No mutation detected in ctDNA
    Number of subjects analysed
    49
    24
    43
    20
    49
    19
    Units: patient
        DCR
    10
    15
    9
    13
    13
    10
        Progression
    32
    8
    30
    6
    31
    7
        Not done / Not evaluable
    7
    1
    4
    1
    5
    2
    No statistical analyses for this end point

    Post-hoc: Post-study Treatment

    		 Close Top of page
    End point title
    		 Post-study Treatment
    End point description
    End point type
    Post-hoc
    End point timeframe
    End of study for each patient.
    End point values
    		 ITT Arm Atezolizumab ITT Arm Chemotherapy
    Number of subjects analysed
    30 [2]
    16 [3]
    Units: patients
        Chemotherapy alone
    25
    11
        Radiotherapy alone
    2
    0
        Chemotherapy + Radiotherapy
    3
    5
        Surgery alone
    0
    0
    Notes
    [2] - 30 patients out of the 46 patients who stopped study treatment had available post-study follow-up.
    [3] - 16 patients out of the 24 patients who stopped study treatment had available post-study follow-up.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AEs were collected from the date of signature of the informed consent until 30 days after the last day of study treatment except for AEs related to study drug, which must be reported until resolution or initiation of further anti-tumor therapy.
    Adverse event reporting additional description
    The maximum grade of adverse events was collected by cycle of treatment.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Anti-PD-L1 atezolizumab
    Reporting group description
    		 Patients in the anti-PD-L1 arm received the treatment atezolizumab 1200 mg IV, every three weeks until progression or inacceptable toxicity.

    Reporting group title
    Conventional chemotherapy
    Reporting group description
    		 Patients in the control arm received up to 6 cycles of conventional chemotherapy i.e. second line oral or IV topotecan (oral 2.3 mg/m² or IV 1.5 mg/m² day 1-5 recommended), or re-induction of carboplatin-etoposide doublet (investigator choice based on center policy).

    Serious adverse events
    		 Anti-PD-L1 atezolizumab Conventional chemotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    24 / 48 (50.00%)
    10 / 24 (41.67%)
         number of deaths (all causes)
    29
    17
         number of deaths resulting from adverse events
    11
    1
    Injury, poisoning and procedural complications
    Spinal fracture
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Superior vena cava syndrome
         subjects affected / exposed
    2 / 48 (4.17%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebellar syndrome
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 24 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 24 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    8 / 48 (16.67%)
    2 / 24 (8.33%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 2
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    Malaise
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 48 (4.17%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic haemorrhage
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    4 / 48 (8.33%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Influenza
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site infection
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelitis
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 24 (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
    Hyponatraemia
         subjects affected / exposed
    1 / 48 (2.08%)
    1 / 24 (4.17%)
         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
    		 Anti-PD-L1 atezolizumab Conventional chemotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    48 / 48 (100.00%)
    23 / 24 (95.83%)
    Investigations
    Weight decreased
         subjects affected / exposed
    9 / 48 (18.75%)
    3 / 24 (12.50%)
         occurrences all number
    18
    3
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 48 (12.50%)
    2 / 24 (8.33%)
         occurrences all number
    10
    3
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    5 / 48 (10.42%)
    8 / 24 (33.33%)
         occurrences all number
    21
    15
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 48 (8.33%)
    1 / 24 (4.17%)
         occurrences all number
    8
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 48 (6.25%)
    1 / 24 (4.17%)
         occurrences all number
    6
    2
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Vascular disorders
    Superior vena cava syndrome
         subjects affected / exposed
    3 / 48 (6.25%)
    0 / 24 (0.00%)
         occurrences all number
    4
    0
    Epistaxis
         subjects affected / exposed
    0 / 48 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    4
    Nervous system disorders
    Neuropathy peripheral
         subjects affected / exposed
    2 / 48 (4.17%)
    5 / 24 (20.83%)
         occurrences all number
    3
    9
    Paraesthesia
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 24 (12.50%)
         occurrences all number
    3
    4
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    17 / 48 (35.42%)
    18 / 24 (75.00%)
         occurrences all number
    31
    50
    General physical health deterioration
         subjects affected / exposed
    10 / 48 (20.83%)
    4 / 24 (16.67%)
         occurrences all number
    11
    5
    Chest pain
         subjects affected / exposed
    8 / 48 (16.67%)
    2 / 24 (8.33%)
         occurrences all number
    10
    4
    Fatigue
         subjects affected / exposed
    4 / 48 (8.33%)
    3 / 24 (12.50%)
         occurrences all number
    7
    4
    Oedema peripheral
         subjects affected / exposed
    3 / 48 (6.25%)
    1 / 24 (4.17%)
         occurrences all number
    5
    1
    Pyrexia
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    10 / 48 (20.83%)
    18 / 24 (75.00%)
         occurrences all number
    19
    62
    Thrombocytopenia
         subjects affected / exposed
    5 / 48 (10.42%)
    12 / 24 (50.00%)
         occurrences all number
    7
    32
    Neutropenia
         subjects affected / exposed
    0 / 48 (0.00%)
    7 / 24 (29.17%)
         occurrences all number
    0
    12
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    6 / 48 (12.50%)
    11 / 24 (45.83%)
         occurrences all number
    6
    15
    Constipation
         subjects affected / exposed
    6 / 48 (12.50%)
    5 / 24 (20.83%)
         occurrences all number
    10
    9
    Vomiting
         subjects affected / exposed
    4 / 48 (8.33%)
    5 / 24 (20.83%)
         occurrences all number
    4
    5
    Diarrhoea
         subjects affected / exposed
    4 / 48 (8.33%)
    4 / 24 (16.67%)
         occurrences all number
    4
    8
    Abdominal pain upper
         subjects affected / exposed
    4 / 48 (8.33%)
    1 / 24 (4.17%)
         occurrences all number
    4
    1
    Abdominal pain
         subjects affected / exposed
    4 / 48 (8.33%)
    1 / 24 (4.17%)
         occurrences all number
    4
    1
    Stomatitis
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 24 (8.33%)
         occurrences all number
    1
    3
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    12 / 48 (25.00%)
    9 / 24 (37.50%)
         occurrences all number
    25
    14
    Cough
         subjects affected / exposed
    8 / 48 (16.67%)
    3 / 24 (12.50%)
         occurrences all number
    15
    4
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    3 / 48 (6.25%)
    2 / 24 (8.33%)
         occurrences all number
    7
    5
    Dry skin
         subjects affected / exposed
    3 / 48 (6.25%)
    0 / 24 (0.00%)
         occurrences all number
    6
    0
    Alopecia
         subjects affected / exposed
    0 / 48 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    4
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    3 / 48 (6.25%)
    0 / 24 (0.00%)
         occurrences all number
    11
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    6 / 48 (12.50%)
    1 / 24 (4.17%)
         occurrences all number
    8
    2
    Arthralgia
         subjects affected / exposed
    3 / 48 (6.25%)
    3 / 24 (12.50%)
         occurrences all number
    9
    5
    Myalgia
         subjects affected / exposed
    3 / 48 (6.25%)
    2 / 24 (8.33%)
         occurrences all number
    4
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 48 (4.17%)
    4 / 24 (16.67%)
         occurrences all number
    3
    4
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    11 / 48 (22.92%)
    9 / 24 (37.50%)
         occurrences all number
    13
    17
    Hyponatraemia
         subjects affected / exposed
    6 / 48 (12.50%)
    3 / 24 (12.50%)
         occurrences all number
    10
    4
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 48 (2.08%)
    2 / 24 (8.33%)
         occurrences all number
    1
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Feb 2017
    Modification of the protocol in the following areas: Recent histological evidence required prior to randomisation, in case of progression more than one year after the end of the previous treatment. Addition of a 3 week delay between the last treatment of the previous line and inclusion of the patient. Correction of the definition of progression-free survival. Correction of the timing of assessments to allow for the assessment of the primary endpoint of the study (response rate at 6 weeks).

    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.
    Choice of ORR as the primary endpoint : it has been reported that there is a frequent lack of consistency between ORR and OS in immune checkpoint inhibitors trials.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/30664989
    http://www.ncbi.nlm.nih.gov/pubmed/33261056
    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-Sat Apr 27 16:11:34 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA