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   43857   clinical trials with a EudraCT protocol, of which   7284   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-centre open label randomised phase III trial of the efficacy of sodium thiosulphate in reducing ototoxicity in patients receiving cisplatin chemotherapy for standard risk hepatoblastoma

    Summary
    EudraCT number
    		 2007-002402-21
    Trial protocol
    		 GB   BE   FR   IE   ES   DK  
    Global end of trial date
    08 May 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Mar 2020
    First version publication date
    13 Mar 2020
    Other versions
    Summary report(s)
    		 SIOPEL 6 - Clinical Trial Summary Report

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RG_09-205
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00652132
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University of Birmingham (Sponsor for UK ONLY)
    Sponsor organisation address
    Edgbaston, Birmingham, United Kingdom, B15 2TT
    Public contact
    Trial Coordinator (for UK ONLY), University of Birmingham (for UK ONLY), 44 01214151061, siopel6@trials.bham.ac.uk
    Scientific contact
    Trial Coordinator, University of Birmingham, 44 01214151061, siopel6@trials.bham.ac.uk
    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
    07 Nov 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 May 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    08 May 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of Sodium Thiosulphate to reduce the hearing impairment caused by Cisplatin chemotherapy.
    Protection of trial subjects
    Early stopping may be warranted in case of convincing evidence that a reduction in hearing impairment by at least 25% is corroborated. Interim analyses were conducted at 1/3 and 2/3 of process time, i.e. after 34 and 68 patients were evaluable for the primary endpoint. If the nominal alpha levels for the test of the primary endpoint were <0.00069 (34 pts), <0.016 (68 pts), early stopping of the trial was to be considered. The final test was to be carried out at nominal alpha level of 0.045. In case of concerns of an adverse effect of STS on the short-term efficacy of the Cisplatin chemotherapy, the trial may be stopped early as well. Interim efficacy results on response to chemotherapy were evaluated after every 20 patients and submitted immediately to the International Data Monitoring Committee (IDMC) and the trial committee. The IDMC and the trial committee independently reviewed the results. The IDMC was to formulate a recommendation to the trial committee. If interim efficacy results observed in this trial were worse than observed in SIOPEL 2 and 3, or if the rate of early progressive disease after 2 cycles had raised concerns, early closure of the trial was to be considered. After each 20 patients (10 per arm), the rates of progression in the two arms and their difference (rate of PD in CIS+STS arm minus (rate of PD in CIS arm) were to be calculated. If the 95% lower confidence limit (LCL) for the difference were above zero this meant that there was a higher rate of early progression in the CIS+STS arm, and the trial would be recommended for closure due to a negative effect of STS on response to chemotherapy.
    Background therapy
    		 -
    Evidence for comparator
    		 N/A
    Actual start date of recruitment
    15 Dec 2007
    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
    United Kingdom: 39
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    France: 36
    Country: Number of subjects enrolled
    Ireland: 2
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    Australia: 5
    Country: Number of subjects enrolled
    Japan: 5
    Country: Number of subjects enrolled
    New Zealand: 3
    Country: Number of subjects enrolled
    Switzerland: 2
    Country: Number of subjects enrolled
    United States: 2
    Worldwide total number of subjects
    113
    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)
    83
    Children (2-11 years)
    30
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 129 patients were registered in the database. Registration was done prior to the eligibility check because SIOPEL’s intent was to register all hepatoblastoma patients irrespective of their inclusion in a therapeutic trial.

    Pre-assignment
    Screening details
    		 Standard-risk hepatoblastoma patients are patients who are considered operable at time of diagnosis. The main eligibility criteria are: • Histologically confirmed newly diagnosed hepatoblastoma • Standard risk hepatoblastoma • PRETEXT I, II or III • Serum alpha-fetoprotein (AFP) > 100 μg/L • No additional PRETEXT criteria • Age ≤ 18 y

    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
    		 Cisplatin alone
    Arm description
    		 Cisplatin alone
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    L01XA01
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For children > 10kg: 80 mg/m2 IV infusion over 6 hours For infants and children 5-10kg: 2.7 mg/kg IV infusion over 6 hours For infants < 5kg: 1.8 mg/kg IV infusion over 6 hours

    Arm title
    		 Cisplatin + STS
    Arm description
    		 Cisplatin + STS
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    L01XA01
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For children > 10kg: 80 mg/m2 IV infusion over 6 hours For infants and children 5-10kg: 2.7 mg/kg IV infusion over 6 hours For infants < 5kg: 1.8 mg/kg IV infusion over 6 hours

    Investigational medicinal product name
    Sodium Thiosulphate
    Investigational medicinal product code
    Other name
    ADH300001
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For children > 10kg: 20 g/m2 IV infusion over 15 minutes For infants and children 5-10kg: 15 g/m2 IV infusion over 15 minutes For infants < 5kg: 10 g/m2 IV infusion over 15 minutes

    Number of subjects in period 1
    		Cisplatin alone Cisplatin + STS
    Started
    53
    60
    Completed
    52
    57
    Not completed
    1
    3
         Re classified as High Risk
    1
    -
         reclassified as high risk
    -
    1
         Consent withdrawn by subject
    -
    1
         Lost to follow-up
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cisplatin alone
    Reporting group description
    		 Cisplatin alone

    Reporting group title
    Cisplatin + STS
    Reporting group description
    		 Cisplatin + STS

    Reporting group values
    		 Cisplatin alone Cisplatin + STS Total
    Number of subjects
    		 53 60 113
    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)
    		 43 43 86
        Children (2-11 years)
    		 10 17 27
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 1.08 (0.25 to 5.9) 1.05 (0.10 to 8.2) -
    Gender categorical
    Units: Subjects
        Female
    		 23 28 51
        Male
    		 30 32 62
    PRETEXT
    PRE-Treatment EXTent of disease
    Units: Subjects
        I/II
    		 31 42 73
        III
    		 22 18 40
    weight class
    Units: Subjects
        less than 5 kg
    		 1 1 2
        5 - 10 kg
    		 27 31 58
        more than 10 kg
    		 24 25 49
        not recorded
    		 1 3 4
    alfa feto protein
    Units: ng/mL
        median (full range (min-max))
    		 76439 (187 to 2175690) 152319 (273 to 4536500) -
    Subject analysis sets

    Subject analysis set title
    randomized and treated (ITT)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    of 113 randomised patients, two received no trial treatment due to parental refusal, and two received no trial treatment because the diagnosis was revised to "high risk hepatoblastoma" shortly after randomisation.

    Subject analysis set title
    ITT evaluable for hearing loss
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    of the 109 randomized and treated patients, 101 have a centrally reviewed hearing assessment

    Subject analysis sets values
    		 randomized and treated (ITT) ITT evaluable for hearing loss
    Number of subjects
    109
    101
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    83
    76
        Children (2-11 years)
    26
    25
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        median (full range (min-max))
    1.08 (0.10 to 8.2)
    1.08 (0.10 to 8.2)
    Gender categorical
    Units: Subjects
        Female
    50
    46
        Male
    59
    55
    PRETEXT
    PRE-Treatment EXTent of disease
    Units: Subjects
        I/II
    72
        III
    37
    weight class
    Units: Subjects
        less than 5 kg
    2
        5 - 10 kg
    58
        more than 10 kg
    49
        not recorded
    4
    alfa feto protein
    Units: ng/mL
        median (full range (min-max))
    130995 (187 to 4536500)

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cisplatin alone
    Reporting group description
    		 Cisplatin alone

    Reporting group title
    Cisplatin + STS
    Reporting group description
    		 Cisplatin + STS

    Subject analysis set title
    randomized and treated (ITT)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    of 113 randomised patients, two received no trial treatment due to parental refusal, and two received no trial treatment because the diagnosis was revised to "high risk hepatoblastoma" shortly after randomisation.

    Subject analysis set title
    ITT evaluable for hearing loss
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    of the 109 randomized and treated patients, 101 have a centrally reviewed hearing assessment

    Primary: Brock grade ≥ 1 hearing loss

    		 Close Top of page
    End point title
    		 Brock grade ≥ 1 hearing loss
    End point description
    End point type
    Primary
    End point timeframe
    after end of trial treatment or at an age of at least 3.5 years, whichever is later (Brock 1991)
    End point values
    		 Cisplatin alone Cisplatin + STS ITT evaluable for hearing loss
    Number of subjects analysed
    46
    55
    101
    Units: yes vs no
        hearing loss
    29
    18
    47
        no hearing loss
    17
    37
    54
    Statistical analysis title
    		 comparison of rates of hearing loss
    Statistical analysis description
    Chisquare test with significance level of 0.05
    Comparison groups
    Cisplatin alone v Cisplatin + STS
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0024 [1]
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 0.81
    Notes
    [1] - To account for the stratification used at randomization, a stratified Cochran-Mantel-Haenzel test was also done (strat: age, PRETEXT, groups of countries). With a p = 0.0021, and a CMH relative risk of 0.52 the results are virtually the same.

    Secondary: Response to preoperative chemotherapy

    		 Close Top of page
    End point title
    		 Response to preoperative chemotherapy
    End point description
    End point type
    Secondary
    End point timeframe
    at end of pre-operative chemotherapy
    End point values
    		 Cisplatin alone Cisplatin + STS randomized and treated (ITT)
    Number of subjects analysed
    52
    57
    109
    Units: subjects
        partial response
    39
    38
    77
        stable disease
    5
    5
    10
        progressive disease
    5
    11
    16
        not evaluable
    3
    3
    6
    No statistical analyses for this end point

    Secondary: Complete resection

    		 Close Top of page
    End point title
    		 Complete resection
    End point description
    End point type
    Secondary
    End point timeframe
    surgery was performed after pre-operative chemotherapy
    End point values
    		 Cisplatin alone Cisplatin + STS randomized and treated (ITT)
    Number of subjects analysed
    52
    57
    109
    Units: subjects
        partial hepatectomy
    48
    53
    101
        total hep & liver transplant
    4
    4
    8
    No statistical analyses for this end point

    Secondary: Complete remission

    		 Close Top of page
    End point title
    		 Complete remission
    End point description
    End point type
    Secondary
    End point timeframe
    at end of all trial treatment
    End point values
    		 Cisplatin alone Cisplatin + STS randomized and treated (ITT)
    Number of subjects analysed
    52
    57
    109
    Units: subjects
        died at surgery
    1
    0
    1
        complete remission
    44
    52
    96
        partial remission
    4
    5
    9
        progressive disease
    2
    0
    2
        not evaluable
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Event free survival (EFS)

    		 Close Top of page
    End point title
    		 Event free survival (EFS)
    End point description
    Event free survival is calculated as difference from date of randomization to first date of an EFS event (progression, relapse or death from any cause)
    End point type
    Secondary
    End point timeframe
    event free survival at time of last follow-up
    End point values
    		 Cisplatin alone Cisplatin + STS randomized and treated (ITT)
    Number of subjects analysed
    52
    57
    109
    Units: subjects
        event free
    41
    46
    87
        experienced an event
    11
    11
    22
    Statistical analysis title
    		 Kaplan-Meier estimation of event free survival
    Comparison groups
    Cisplatin alone v Cisplatin + STS
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 2.06
    Notes
    [2] - event-free survival is presented in a descriptive manner only and not formally compared between the two arms

    Secondary: Overall survival (OS)

    		 Close Top of page
    End point title
    		 Overall survival (OS)
    End point description
    Overall survival is calculated as difference from date of randomization to date of death from any cause.
    End point type
    Secondary
    End point timeframe
    overall survival at a median follow-up of 52 months
    End point values
    		 Cisplatin alone Cisplatin + STS randomized and treated (ITT)
    Number of subjects analysed
    52
    57
    109
    Units: subjects
        alive
    48
    55
    103
        dead
    4
    2
    6
    Statistical analysis title
    		 Kaplan-Meier estimation of overall survival
    Comparison groups
    Cisplatin + STS v Cisplatin alone
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.08
         upper limit
    		 2.41

    Secondary: Toxicity as graded by CTCAE v 3.0

    		 Close Top of page
    End point title
    		 Toxicity as graded by CTCAE v 3.0
    End point description
    only grade 3, 4 and 5 adverse events were to be reported. CTCAE v 3.0 was to be used for grading adverse events.
    End point type
    Secondary
    End point timeframe
    adverse events observed during pre- and post-operative chemotherapy
    End point values
    		 Cisplatin alone Cisplatin + STS randomized and treated (ITT)
    Number of subjects analysed
    52
    57
    109
    Units: subjects
        allergy
    1
    0
    1
        febrile neutropenia
    10
    8
    18
        infection
    16
    13
    29
        hypomagnesemia
    1
    1
    2
        hypernatremia
    0
    1
    1
        vomiting
    2
    4
    6
        nausea
    3
    2
    5
        left ventricular systolic dysfunction
    0
    0
    0
        renal event
    0
    0
    0
        anemia
    8
    11
    19
        leukopenia
    2
    2
    4
        neutropenia
    6
    10
    16
        thrombocytopenia
    2
    2
    4
        gastrointestinal event
    2
    3
    5
        elevated liver-enzyme level
    6
    4
    10
        elevated serum glucose level
    2
    1
    3
        hypermagnesemia
    2
    5
    7
        hypophosphatemia
    0
    5
    5
        hyperkalemia
    2
    0
    2
        hypokalemia
    0
    5
    5
        dyspnea
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Feasibility of central audiology review

    		 Close Top of page
    End point title
    		 Feasibility of central audiology review
    End point description
    All audiology evaluations had to be based on pure tone audiometry at 8, 6, 4, 2, 1 and 0.5 kHz. The investigator had to submit results by uploading the audiogram into the database. The central reviewer then evaluated the uploaded material, decided whether the investigation had been done according to protocol and fulfilled the criteria to be accepted as final result, and if yes, adjudicated the Brock Grade. Several sites submitted partial audiograms or simple descriptions only which meant that the evaluation was not acceptable and had to be repeated at the next scheduled visit. Other audiograms were judged by the central reviewer as not having been done in a reliable fashion; these had to be repeated as well. Definitive audiology was available for 101 patients, 46 in the Cis alone arm and 55 in the Cis+STS arm. Five patients died before a reliable hearing assessment could be done; two could not be assessed due to their condition (one syndromic, one autistic); one was lost to followup
    End point type
    Secondary
    End point timeframe
    central review of submitted audiograms was done during the conduct of the trial
    End point values
    		 Cisplatin alone Cisplatin + STS randomized and treated (ITT)
    Number of subjects analysed
    52
    57
    109
    Units: subjects
        central review feasible
    46
    55
    101
        died before audiometry
    4
    1
    5
        not assessable (syndromic/autistic)
    1
    1
    2
        lost to follow-up
    1
    0
    1
    No statistical analyses for this end point

    Secondary: long-term renal clearance

    		 Close Top of page
    End point title
    		 long-term renal clearance
    End point description
    Long term development of renal function is of interest since cisplatin may affect renal function permanently. Renal monitoring was done during chemotherapy, at the end of treatment and at follow-up. Glomerular filtration rate was determined through the Cr51 EDTA method, Iohexol, isotope GFR, or calculated from serum creatinine. For many patients, no GFR was recorded in follow-up. For such cases, a serum creatinine value was therefore collected retrospectively. For the calculation of GFR in ml/min/1.73m2 from serum creatinine (Scr), the Schwartz equation (Schwartz 1976) was used: CrCl (ml/min/1.73m2) = [length (cm) × k] / Scr in mg/dL where k = 0.45 for infants 1 to 52 weeks old k = 0.55 for children 1 to 13 years old k = 0.55 for adolescent females 13-18 years old k = 0.7 for adolescent males 13-18 years old the results are reported as *change in GFR* from pre-treatment to last follow-up
    End point type
    Secondary
    End point timeframe
    change in renal clearance from baseline (time of diagnosis or early in treatment) to last follow-up with documented clearance
    End point values
    		 Cisplatin alone Cisplatin + STS randomized and treated (ITT)
    Number of subjects analysed
    49 [3]
    57
    106 [4]
    Units: change in clearance (ml/min/1.73m2)
        median (inter-quartile range (Q1-Q3))
    -6 (-35.2 to 5.0)
    -12 (-39.0 to 21.7)
    -7.5 (-37.2 to 15.9)
    Notes
    [3] - one patient had no baseline value, and two patients had no value in the follow-up period
    [4] - one patient had no baseline value, and two patients had no values recorded in follow-up
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the date of commencement protocol defined treatment until 30 days after the administration of the last treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    3.0
    Reporting groups
    Reporting group title
    Cisplatin alone
    Reporting group description
    		 Cisplatin alone

    Reporting group title
    Cisplatin + STS
    Reporting group description
    		 Cisplatin + STS

    Serious adverse events
    		 Cisplatin alone Cisplatin + STS
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 52 (30.77%)
    13 / 57 (22.81%)
         number of deaths (all causes)
    4
    1
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Thrombosis
    Additional description: Deep vein thrombosis or cardiac thrombosis; intervention (e.g., anticoagulation, lysis, filter, invasive procedure) indicated
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Intraoperative Injury
    Additional description: Primary repair of injured organ/structure indicated
         subjects affected / exposed
    0 / 52 (0.00%)
    2 / 57 (3.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fever
    Additional description: Fever (in the absence of neutropenia, where neutropenia is defined as ANC<1.0 x 10e9/L)
         subjects affected / exposed
    4 / 52 (7.69%)
    5 / 57 (8.77%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Allergy to chemicals
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea
    Additional description: Dyspnea with ADL
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Pain
    Additional description: Moderate pain; pain or analgesics interfering with function, but not interfering with ADL
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Blood and lymphatic system disorders
    Neutrophil count
    Additional description: <1000 - 500/mm(3) <1.0 - 0.5 x 10e9 /L
         subjects affected / exposed
    0 / 52 (0.00%)
    8 / 57 (14.04%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin
    Additional description: <8.0 - 6.5 g/dL <4.9 - 4.0 mmol/L <80 - 65 g/L
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PTT (Partial Thromboplastin Time)
    Additional description: >2 x ULN
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphatic disorder
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulation time
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Enteritis
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 57 (1.75%)
         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
    Rash
    Additional description: Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering <50% of body surface area (BSA)
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Wound
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Febrile neutropenia
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    8 / 52 (15.38%)
    8 / 57 (14.04%)
         occurrences causally related to treatment / all
    2 / 7
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 57 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Cisplatin alone Cisplatin + STS
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 52 (84.62%)
    52 / 57 (91.23%)
    Investigations
    PTT
    Additional description: >2xULN
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences all number
    1
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 52 (0.00%)
    5 / 57 (8.77%)
         occurrences all number
    0
    5
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    8 / 52 (15.38%)
    11 / 57 (19.30%)
         occurrences all number
    8
    11
    Leukopenia
         subjects affected / exposed
    2 / 52 (3.85%)
    2 / 57 (3.51%)
         occurrences all number
    2
    2
    Neutropenia
         subjects affected / exposed
    6 / 52 (11.54%)
    10 / 57 (17.54%)
         occurrences all number
    6
    10
    Gastrointestinal disorders
    Gastrointestinal
         subjects affected / exposed
    2 / 52 (3.85%)
    3 / 57 (5.26%)
         occurrences all number
    2
    3
    Respiratory, thoracic and mediastinal disorders
    Dyspnea
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Thrombocytopenia
         subjects affected / exposed
    2 / 52 (3.85%)
    2 / 57 (3.51%)
         occurrences all number
    2
    2
    Metabolism and nutrition disorders
    Weight loss
    Additional description: >20%
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 57 (0.00%)
         occurrences all number
    1
    0
    Elevated liver enzymes
         subjects affected / exposed
    6 / 52 (11.54%)
    3 / 57 (5.26%)
         occurrences all number
    6
    3
    Hyper HDL cholesterolaemia
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 57 (1.75%)
         occurrences all number
    0
    1
    Hyperglycemia
         subjects affected / exposed
    2 / 52 (3.85%)
    1 / 57 (1.75%)
         occurrences all number
    2
    1
    Hypermagnesemia
    Additional description: The protocol specified the addition of magnesium to the cisplatin hydration fluid.
         subjects affected / exposed
    2 / 52 (3.85%)
    5 / 57 (8.77%)
         occurrences all number
    2
    5
    Hypophosphatemia
         subjects affected / exposed
    0 / 52 (0.00%)
    5 / 57 (8.77%)
         occurrences all number
    0
    5
    Hyperkalemia
         subjects affected / exposed
    2 / 52 (3.85%)
    0 / 57 (0.00%)
         occurrences all number
    2
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Aug 2010
    SA-04 Protocol v3.0 vd19-Aug-2010 Change of Sponsor (UK Only). With associated documents, Participant Consent Forms, Participant Information Sheets, GP/Consultant Information Letter, IMP labels and Data Transfer letters.
    10 Aug 2012
    SA-09 Protocol v4.0 vd18-Jul-2012 (UK Only). With associated documents, Participant Consent Forms, Participant Information Sheets and GP/Consultant Information Sheet.
    01 Feb 2015
    SA-11 Protocol v5.0 vd01-Feb-2015, change of sampling procedures and hydration requirements (UK Only). With associated documents, Addendum A Informed Consent Form and Patient Information Sheet,

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/29924955
    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-Wed Apr 24 20:48:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA