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 Multi-center, Open-Label, Adaptive, Randomized Study of Palifosfamidetris, a Novel DNA Crosslinker, in Combination with Carboplatin and Etoposide (PaCE) Chemotherapy versus Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients with Extensive-Stage Small Cell Lung Cancer

    Summary
    EudraCT number
    		 2011-006134-17
    Trial protocol
    		 GB   HU   PL   IT   DE   FR  
    Global end of trial date
    02 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Apr 2016
    First version publication date
    17 Apr 2016
    Other versions
    Summary report(s)
    		 IPM3002 CSR Summary

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IPM3002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01555710
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ZIOPHARM Oncology Inc.
    Sponsor organisation address
    One First Avenue, Parris Building 34, Navy Yard Plaza, Boston MA, United States, 02129
    Public contact
    Caesar Belbel, ZIOPHARM Oncology Inc., +1 617 259-1641, cbelbel@ziopharm.com
    Scientific contact
    Francois Lebel, ZIOPHARM Oncology Inc., +1 617 778-1756, flebel@ziopharm.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 Apr 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Dec 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Dec 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to compare the efficacy of palifosfamide-tris in combination with carboplatin and etoposide (PaCE) chemotherapy to carboplatin and etoposide (CE) alone, as measured by overall survival (OS), in chemotherapy naïve subjects with extensivestage SCLC
    Protection of trial subjects
    This study was performed in compliance with Good Clinical Practices (GCP), including the archiving of essential documents.
    Background therapy
    		 Carboplatin and etoposide were obtained by each study center as commercially available drug products and stored/used per label instructions. For those sites in the European Union that were not able to obtain the comparators commercially, the Sponsor provided the comparator products. Lot numbers N09770 Carboplatin 450 mg/45 mL, N10216 Carboplatin 50 mg/5 mL, 12G02LC Etoposide-Teva active 200 mg/10 mL
    Evidence for comparator
    		 Carboplatin and etoposide were obtained by each study center as commercially available drug products and stored/used per label instructions. For those sites in the European Union that were not able to obtain the comparators commercially, the Sponsor provided the comparator products. Lot numbers N09770 Carboplatin 450 mg/45 mL, N10216 Carboplatin 50 mg/5 mL, 12G02LC Etoposide-Teva active 200 mg/10 mL
    Actual start date of recruitment
    08 Jun 2012
    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
    Australia: 4
    Country: Number of subjects enrolled
    Russian Federation: 45
    Country: Number of subjects enrolled
    Taiwan: 3
    Country: Number of subjects enrolled
    Ukraine: 17
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    United Kingdom: 13
    Country: Number of subjects enrolled
    France: 15
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Hungary: 3
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    United States: 60
    Country: Number of subjects enrolled
    Canada: 14
    Country: Number of subjects enrolled
    Israel: 4
    Worldwide total number of subjects
    188
    EEA total number of subjects
    41
    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)
    118
    From 65 to 84 years
    70
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment was initiated on 08 Jun 2012 (first subject enrolled) to 02 Dec 2014 (last subject last follow-up) in a total of 12 countries globally.

    Pre-assignment
    Screening details
    		 Screening tests are specified in the Protocol Section 5, Schedule of Study Procedures and Assessments. Principal Investigators (PIs) at each site are responsible for maintaining a record of all subjects screened, including both those who enter the study and those who are excluded.

    Period 1
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Open-label trial design

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Palifosfamide-tris with Carboplatin and Etoposide
    Arm description
    		 Palifosfamide-tris, a Novel DNA Crosslinker, in Combination with Carboplatin and Etoposide (PaCE) Chemotherapy: PaCE chemotherapy consisting of palifosfamide-tris (130 mg/m2/day) and etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 4 mg/mL/min [maximum of 600 mg]) on Day 1 of a 21-day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Palifosfamide-tris
    Investigational medicinal product code
    Palifosfamide
    Other name
    Zymafos, ZIO-201
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    130 mg/m2 milligram(s)/square meter per day. Intravenous use.

    Arm title
    		 Carboplatin and Etoposide (CE) Chemotherapy
    Arm description
    		 Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients with Extensive-Stage Small Cell Lung Cancer: control group received CE chemotherapy consisting of etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 5 mg/mL/min [maximum of 750 mg]) on Day 1 of a 21-day treatment cycle.
    Arm type
    		 Background therapy

    Investigational medicinal product name
    Carboplatin and Etoposide
    Investigational medicinal product code
    CE
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    The control group received CE chemotherapy consisting of etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 5 mg/mL/min [maximum of 750 mg]) on Day 1 of a 21-day treatment cycle.

    Number of subjects in period 1
    		Palifosfamide-tris with Carboplatin and Etoposide Carboplatin and Etoposide (CE) Chemotherapy
    Started
    94
    94
    Completed
    94
    94

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Palifosfamide-tris with Carboplatin and Etoposide
    Reporting group description
    		 Palifosfamide-tris, a Novel DNA Crosslinker, in Combination with Carboplatin and Etoposide (PaCE) Chemotherapy: PaCE chemotherapy consisting of palifosfamide-tris (130 mg/m2/day) and etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 4 mg/mL/min [maximum of 600 mg]) on Day 1 of a 21-day treatment cycle.

    Reporting group title
    Carboplatin and Etoposide (CE) Chemotherapy
    Reporting group description
    		 Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients with Extensive-Stage Small Cell Lung Cancer: control group received CE chemotherapy consisting of etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 5 mg/mL/min [maximum of 750 mg]) on Day 1 of a 21-day treatment cycle.

    Reporting group values
    		 Palifosfamide-tris with Carboplatin and Etoposide Carboplatin and Etoposide (CE) Chemotherapy Total
    Number of subjects
    		 94 94 188
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 59 59 118
        From 65-84 years
    		 35 35 70
        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
        85 years and over
    		 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 28 28 56
        Male
    		 66 66 132

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Palifosfamide-tris with Carboplatin and Etoposide
    Reporting group description
    		 Palifosfamide-tris, a Novel DNA Crosslinker, in Combination with Carboplatin and Etoposide (PaCE) Chemotherapy: PaCE chemotherapy consisting of palifosfamide-tris (130 mg/m2/day) and etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 4 mg/mL/min [maximum of 600 mg]) on Day 1 of a 21-day treatment cycle.

    Reporting group title
    Carboplatin and Etoposide (CE) Chemotherapy
    Reporting group description
    		 Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients with Extensive-Stage Small Cell Lung Cancer: control group received CE chemotherapy consisting of etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 5 mg/mL/min [maximum of 750 mg]) on Day 1 of a 21-day treatment cycle.

    Primary: Efficacy end point

    		 Close Top of page
    End point title
    		 Efficacy end point
    End point description
    Survival was measured from the date of randomization. Follow-up information included vital status and interim cancer history (e.g., anticancer treatments received). This information was recorded at least every 12 ± 2 weeks following the post-treatment safety assessment visit until the targeted number of deaths was observed or until 1 year following the completion of enrollment, whichever was later.
    End point type
    Primary
    End point timeframe
    Overall survival - Time (months)
    End point values
    		 Palifosfamide-tris with Carboplatin and Etoposide Carboplatin and Etoposide (CE) Chemotherapy
    Number of subjects analysed
    92
    91
    Units: Time (months)
        number (not applicable)
    10.03
    10.37
    Statistical analysis title
    		 Efficacy analysis:
    Statistical analysis description
    Median OS times for the PaCE (10.03 months) and CE (10.37 months) chemotherapy groups were not significantly different (p=0.096). Overall, median OS was consistent with study assumptions. The Cox proportional HR without interactions favored CE chemotherapy and the difference was statistically significant (p=0.031) after adjustment for baseline age category, gender, ECOG PS, and region. A Cox proportional hazards regression with interactions was also performed.
    Comparison groups
    Palifosfamide-tris with Carboplatin and Etoposide v Carboplatin and Etoposide (CE) Chemotherapy
    Number of subjects included in analysis
    183
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.096
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 0.95
         upper limit
    		 1.78
    Variability estimate
    Standard deviation
    Notes
    [1] - Median OS times for the PaCE (10.03 months) and CE (10.37 months) chemotherapy groups were not significantly different (p=0.096).

    Secondary: Safety: assess progression free survival

    		 Close Top of page
    End point title
    		 Safety: assess progression free survival
    End point description
    Secondary: -Assess potential prognostic factors for OS (i.e., Eastern Cooperative Oncology Group performance status [ECOG PS], age, gender, and region) -Assess the safety as characterized by serious adverse events (SAEs)
    End point type
    Secondary
    End point timeframe
    Overall survival:
    End point values
    		 Palifosfamide-tris with Carboplatin and Etoposide Carboplatin and Etoposide (CE) Chemotherapy
    Number of subjects analysed
    92
    91
    Units: Percentage SAE events per arm
    20
    20
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    The safety of study treatments was assessed by the frequency and severity of SAEs within the overall survival timeframe defined by the protocol, including follow-up after treatment.
    Adverse event reporting additional description
    An AE was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug related. Treatment-emergent AEs defined if started on or after the date of treatment with study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13
    Reporting groups
    Reporting group title
    Palifosfamide-tris with Carboplatin and Etoposide
    Reporting group description
    		 Palifosfamide-tris, a Novel DNA Crosslinker, in Combination with Carboplatin and Etoposide (PaCE) Chemotherapy: PaCE chemotherapy consisting of palifosfamide-tris (130 mg/m2/day) and etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 4 mg/mL/min [maximum of 600 mg]) on Day 1 of a 21-day treatment cycle.

    Reporting group title
    Carboplatin and Etoposide (CE) Chemotherapy
    Reporting group description
    		 Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients with Extensive-Stage Small Cell Lung Cancer: control group received CE chemotherapy consisting of etoposide (100 mg/m2/day) on Days 1, 2, and 3, and carboplatin (target AUC of 5 mg/mL/min [maximum of 750 mg]) on Day 1 of a 21-day treatment cycle.

    Serious adverse events
    		 Palifosfamide-tris with Carboplatin and Etoposide Carboplatin and Etoposide (CE) Chemotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 92 (17.39%)
    16 / 91 (17.58%)
         number of deaths (all causes)
    83
    76
         number of deaths resulting from adverse events
    1
    1
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Congenital, familial and genetic disorders
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Vascular disorders
         subjects affected / exposed
    1 / 92 (1.09%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac disorder
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Nervous system disorder
         subjects affected / exposed
    1 / 92 (1.09%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood disorder
         subjects affected / exposed
    8 / 92 (8.70%)
    8 / 91 (8.79%)
         occurrences causally related to treatment / all
    11 / 11
    9 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General disorder
    Additional description: disease progression
         subjects affected / exposed
    2 / 92 (2.17%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal disorder
         subjects affected / exposed
    6 / 92 (6.52%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    6 / 7
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychiatric disorders
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and connective tissue disorders
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Infections and infestations
    Infections and infestations
         subjects affected / exposed
    2 / 92 (2.17%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Metabolism and nutrition disorders
    Metabolism and nutrition disorders
         subjects affected / exposed
    2 / 92 (2.17%)
    2 / 91 (2.20%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Palifosfamide-tris with Carboplatin and Etoposide Carboplatin and Etoposide (CE) Chemotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 92 (2.17%)
    4 / 91 (4.40%)
    Nervous system disorders
    Nervous system disorder
         subjects affected / exposed
    2 / 92 (2.17%)
    4 / 91 (4.40%)
         occurrences all number
    4
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Apr 2013
    Amendment to protocol to enable a temporary halt to recruitment

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    26 Apr 2013
    Recruitment to this study was halted by the sponsor due to a strategic re-direction of the program and to allow an interim analysis of data.
    -

    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-Thu May 02 17:01:23 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA