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 phase III clinical trial to evaluate patient´s preference of subcutaneous trastuzumab (SC) versus intravenous (IV) administration in patients with HER2 positive Advanced Breast Cancer (ABC) who have received intravenous trastuzumab at least 4 months and without disease progression

    Summary
    EudraCT number
    		 2012-004928-38
    Trial protocol
    		 ES  
    Global end of trial date
    30 Apr 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Oct 2020
    First version publication date
    29 Oct 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GEICAM/2012-07
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01875367
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GEICAM (FUNDACIÓN GRUPO ESPAÑOL DE INVESTIGACIÓN EN CÁNCER DE MAMA)
    Sponsor organisation address
    Avenida de los Pirineos 7, San Sebastián de los Reyes / Madrid, Spain, 28703
    Public contact
    GEICAM, GEICAM (Fundación Grupo Español de Investigación en Cáncer de Mama), 0034 916592870, inicio_ensayos@geicam.org
    Scientific contact
    GEICAM, GEICAM (Fundación Grupo Español de Investigación en Cáncer de Mama), 0034 916592870, inicio_ensayos@geicam.org
    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 Apr 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Apr 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To analyze the percentage of patients who indicate a preference for the use of the subcutaneous vs the intravenous administration of trastuzumab.
    Protection of trial subjects
    Not applicable. It was not necessary to applied extra measures for protection of the subjects out of the good clinical practice environment.
    Background therapy
    		 HER2 receptor is involved in cell growth control, differentiation, and survival (Gschwind, Fischer, & Ullrich, 2004; Yarden & Sliwkowski, 2001). HER2 oncogen, overexpressed in 20%-30% of breast cancer (BC) patients, is associated with aggressive tumor characteristics and poor prognosis (Slamon et al., 1987; Slamon et al., 1989). (Menard, Fortis, Castiglioni, Agresti, & Balsari, 2001; Ross & Fletcher, 1998). Trastuzumab, a humanized anti-HER2 monoclonal antibody, is the standard of care in monotherapy or in combination. As far as 1-year of treatment in the early disease setting and maintenance therapy in patients with metastatic breast cancer (MBC) is recommended, HER2-positive BC patients undergo long periods on trastuzumab therapy. Standard trastuzumab is administered intravenously (IV-t) according to weight every 3 weeks. IV-t initial administration lasts 90min and subsequent 30min, resulting in infusion reactions, venous access problems, long administration and observation periods, frequent visits to hospital, and the need for reloading dosages in case of treatment delays.
    Evidence for comparator
    		 The subcutaneous formulation of trastuzumab (SC-t) was developed as an alternative to the IV formulation and it is administered as a 600mg-fixed dose, combined with 10,000U of recombinant human hyaluronidase (rHuPH20), in a single injection (vial) or in a single injection device (SID) in 5-minutes. SC-t shortens administration time and errors by eliminating weightbased dose loading. Whereas HannaH, PrefHER and SafeHER studies showed that pharmacokinetics, efficacy and safety of SC-t was comparable to IV-t in early HER2-positive BC (Gligorov et al., 2017; Ismael et al., 2012; Pivot et al., 2017), data for MBC patients are lacking. Our aim was to evaluate HER2-positive MBC patients´ preference for IV-t versus SC-t.
    Actual start date of recruitment
    18 Sep 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 166
    Worldwide total number of subjects
    166
    EEA total number of subjects
    166
    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)
    105
    From 65 to 84 years
    57
    85 years and over
    4

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 From September 2013 to July 2015, 166 patients were randomized (81 to arm A [vial to SID] and 85 to arm B [SID to vial]) in 26 GEICAM Spanish Breast Cancer Group sites.

    Pre-assignment
    Screening details
    		 From September 2013 to July 2015, 166 patients were randomized (81 to arm A [vial to SID] and 85 to arm B [SID to vial]) in 26 GEICAM Spanish Breast Cancer Group sites.

    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
    		 T-SC Vial + T-SC Device
    Arm description
    		 Trastuzumab Injectable Solution: Subcutaneous (SC) injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles Trastuzumab Injectable Solution: Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles. Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trastuzumab subcutaneous inyection vial
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles.

    Investigational medicinal product name
    Trastuzumab subcutaneous device administration
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles

    Arm title
    		 T-SC Device + T-SC Vial
    Arm description
    		 Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles Trastuzumab Injectable Solution: Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles. Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trastuzumab subcutaneous inyection vial
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles.

    Investigational medicinal product name
    Trastuzumab subcutaneous device administration
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles

    Number of subjects in period 1
    		T-SC Vial + T-SC Device T-SC Device + T-SC Vial
    Started
    81
    85
    Completed
    76
    83
    Not completed
    5
    2
         Not receive study treatment
    1
    -
         Not complete at least 2 questionaries
    4
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    T-SC Vial + T-SC Device
    Reporting group description
    		 Trastuzumab Injectable Solution: Subcutaneous (SC) injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles Trastuzumab Injectable Solution: Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles. Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles

    Reporting group title
    T-SC Device + T-SC Vial
    Reporting group description
    		 Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles Trastuzumab Injectable Solution: Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles. Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles

    Reporting group values
    		 T-SC Vial + T-SC Device T-SC Device + T-SC Vial Total
    Number of subjects
    		 81 85 166
    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)
    		 0
        Children (2-11 years)
    		 0
        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))
    		 63 (35 to 93) 58 (38 to 85) -
    Gender categorical
    Units: Subjects
        Female
    		 81 85 166
        Male
    		 0 0 0
    Race
    Units: Subjects
        Caucasian
    		 78 83 161
        Black
    		 1 0 1
        Hispanic
    		 1 0 1
        Arabian
    		 1 2 3
    Menopausal status
    Units: Subjects
        Premenopausal
    		 8 12 20
        Postmenopausal
    		 73 73 146
    Eastern Cooperative Oncology Group (ECOG) performance status
    Measure Description: ECOG score runs from 0 to 5, with 0 denoting perfect health and 5 death. 0 - Asymptomatic 1 - Symptomatic but completely ambulatory 2 - Symptomatic, <50% in bed during the day 3 - Symptomatic, >50% in bed, but not bedbound 4 - Bedbound 5 - Death
    Units: Subjects
        ECOG 0
    		 63 61 124
        ECOG 1
    		 17 24 41
        ECOG 2
    		 1 0 1
    Estrogen Receptor
    A cancer is called hormonal receptor positive if it has receptors for progesterone or estrogen. This suggests that the cancer cells, like normal breast cells, may receive signals from progesterone or estrogen that could promote their growth. If the cancer is hormone-receptor-negative (no receptors are present), then hormonal therapy is unlikely to work.
    Units: Subjects
        Positive
    		 46 60 106
        Negative
    		 35 25 60
    Progesterone Receptor
    A cancer is called hormonal receptor positive if it has receptors for progesterone or estrogen. This suggests that the cancer cells, like normal breast cells, may receive signals from progesterone or estrogen that could promote their growth. If the cancer is hormone-receptor-negative (no receptors are present), then hormonal therapy is unlikely to work.
    Units: Subjects
        Negative
    		 50 38 88
        Positive
    		 31 47 78
    Other anti HER2 therapy at registration
    Units: Subjects
        Pertuzumab
    		 8 11 19
        Lapatinib
    		 3 5 8
        No anti HER2 therapy
    		 70 69 139
    Treatment combined with trastuzumab at registration
    Units: Subjects
        Hormonotherapy
    		 34 36 70
        Chamotherapy
    		 12 9 21
        Other anticancertherapy
    		 7 10 17
        Other anticancer therapy plus Chemotherapyplus
    		 2 4 6
        Other anticancer therapy plus Hormonotherapy plus
    		 2 2 4
        No other anticancer therapy
    		 24 24 48
    Administration route at registration
    Units: Subjects
        Intravenous
    		 25 27 52
        Intramuscular
    		 5 5 10
        Subcutaneous
    		 4 5 9
        Oral
    		 25 29 54
        None
    		 22 19 41
    Metastases at diagnosis
    Units: Subjects
        No
    		 53 52 105
        Yes
    		 28 33 61
    Visceral metastases at registration
    Units: Subjects
        Yes
    		 41 49 90
        No
    		 40 36 76
    Bone metastases at registration
    Units: Subjects
        Yes
    		 34 41 75
        No
    		 47 44 91
    Skin/soft tissue/lymph nodes metastases at registration
    Units: Subjects
        Yes
    		 31 29 60
        No
    		 50 56 106
    Time with IV trastuzumab for metastasis at registration
    Units: Years
        median (full range (min-max))
    		 1.9 (0.35 to 13.67) 1.78 (0.34 to 14.05) -
    Prior treatment lines at registration
    Units: Treatment lines
        median (full range (min-max))
    		 1 (1 to 7) 1 (1 to 7) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    T-SC Vial + T-SC Device
    Reporting group description
    		 Trastuzumab Injectable Solution: Subcutaneous (SC) injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles Trastuzumab Injectable Solution: Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles. Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles

    Reporting group title
    T-SC Device + T-SC Vial
    Reporting group description
    		 Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles Trastuzumab Injectable Solution: Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles. Trastuzumab Injectable Product: Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles

    Primary: Percentage of Treatment Preference

    		 Close Top of page
    End point title
    		 Percentage of Treatment Preference
    End point description
    The percentage of patients who indicate a preference for the use of the intravenous vs subcutaneous administration of trastuzumab was analyzed with the answer to the questionnaire C2 (question number 39) of experiences and preferences of the patient.
    End point type
    Primary
    End point timeframe
    Up to 12 weeks
    End point values
    		 T-SC Vial + T-SC Device T-SC Device + T-SC Vial
    Number of subjects analysed
    76
    83
    Units: Preference
        Subcutaneous
    66
    71
        Intravenous
    6
    5
        No preference
    4
    7
    Statistical analysis title
    		 Proportion estimation
    Statistical analysis description
    Percent preference of SC in both arms was calculated and 95% confidential interval and it was compared with the 75% prefixed.
    Comparison groups
    T-SC Vial + T-SC Device v T-SC Device + T-SC Vial
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0008
    Method
    		 Chi-squared
    Parameter type
    		 percentage
    Point estimate
    86.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 79.8
         upper limit
    		 91.1
    Variability estimate
    Standard deviation

    Secondary: Percentage of Subcutaneous Treatment (Vial vs Device Administration) Preference

    		 Close Top of page
    End point title
    		 Percentage of Subcutaneous Treatment (Vial vs Device Administration) Preference
    End point description
    The percentage of patients who indicate a preference for the use of SC administration by road or device was analyzed. This was discussed in the answer to question number 28 of the questionnaire of experiences and preferences of the patient.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    End point values
    		 T-SC Vial + T-SC Device T-SC Device + T-SC Vial
    Number of subjects analysed
    70
    77
    Units: Patients
        Subcutaneous
    46
    44
        Intravenous
    20
    20
        No preference
    4
    13
    No statistical analyses for this end point

    Secondary: Medical Staff Satisfaction Intravenous vs Subcutaneous

    		 Close Top of page
    End point title
    		 Medical Staff Satisfaction Intravenous vs Subcutaneous [1]
    End point description
    The medical staff satisfaction was analyzed with the answers to question number 33a of the questionnaire of experiences and preferences of the medical staff.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The medical staff satisfaction has been analysed taken into account only the device type, and no the arm. It is the preference of health staff and is a different sample from both arms.
    End point values
    		 T-SC Vial + T-SC Device
    Number of subjects analysed
    39
    Units: Answers from questionnaire
        Subcutaneous
    34
        Intravenous
    0
        No differences
    4
        Not answered
    1
    No statistical analyses for this end point

    Secondary: Medical Staff Satisfaction Subcutaneous Device vs Vial

    		 Close Top of page
    End point title
    		 Medical Staff Satisfaction Subcutaneous Device vs Vial [2]
    End point description
    The medical staff satisfaction was analyzed with the answers to question number 33b of the questionnaire of experiences and preferences of the medical staff.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The medical staff satisfaction has been analysed taken into account only the device type, and no the arm. It is the preference of health staff and is a different sample from both arms.
    End point values
    		 T-SC Device + T-SC Vial
    Number of subjects analysed
    39
    Units: Answers from questionnaire
        Preferred device
    20
        Preferred vial
    11
        No Preference
    8
    No statistical analyses for this end point

    Secondary: The Number of Participants Who Experienced Adverse Events (AE)

    		 Close Top of page
    End point title
    		 The Number of Participants Who Experienced Adverse Events (AE)
    End point description
    Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03.
    End point type
    Secondary
    End point timeframe
    Through study treatment, an average of 16 weeks
    End point values
    		 T-SC Vial + T-SC Device T-SC Device + T-SC Vial
    Number of subjects analysed
    81
    85
    Units: Events
        The Number of Participants Who Experienced Adverse
    76
    84
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 NCI-CTCAE
    Dictionary version
    4.03
    Reporting groups
    Reporting group title
    T-SC Vial + T-SC Device
    Reporting group description
    		 -

    Reporting group title
    T-SC Device + T-SC Vial
    Reporting group description
    		 -

    Serious adverse events
    		 T-SC Vial + T-SC Device T-SC Device + T-SC Vial
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 81 (2.47%)
    10 / 85 (11.76%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gastric cancer
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Heart Failure
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Stroke
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fever
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Nodule in left breast
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nodule in right breast
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgery for surgical castration
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hematuria
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (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
    Lack of strength in left leg
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ostenecrosis produced by biphosphonates
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cold
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter related infection (Bacteriemia)
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences causally related to treatment / all
    0 / 0
    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
    		 T-SC Vial + T-SC Device T-SC Device + T-SC Vial
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    76 / 81 (93.83%)
    84 / 85 (98.82%)
    Investigations
    Platelet count decreased grade 4
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Platelet count decreased grade 1
         subjects affected / exposed
    4 / 81 (4.94%)
    8 / 85 (9.41%)
         occurrences all number
    4
    8
    Creatinine increased grade 4
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences all number
    0
    1
    Creatinine increased grade 2
         subjects affected / exposed
    1 / 81 (1.23%)
    2 / 85 (2.35%)
         occurrences all number
    1
    2
    Creatinine increased grade 1
         subjects affected / exposed
    13 / 81 (16.05%)
    17 / 85 (20.00%)
         occurrences all number
    13
    17
    Alanine aminotransferase increased grade 3
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences all number
    0
    1
    Alanine aminotransferase increased grade 2
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences all number
    0
    1
    Alanine aminotransferase increased grade 1
         subjects affected / exposed
    16 / 81 (19.75%)
    10 / 85 (11.76%)
         occurrences all number
    16
    10
    Aspartate aminotransferase increased grade 3
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences all number
    0
    1
    Aspartate aminotransferase increased grade 1
         subjects affected / exposed
    15 / 81 (18.52%)
    17 / 85 (20.00%)
         occurrences all number
    15
    17
    Alkaline phosphatase increased grade 3
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Alkaline phosphatase increased grade 2
         subjects affected / exposed
    1 / 81 (1.23%)
    2 / 85 (2.35%)
         occurrences all number
    1
    2
    Alkaline phosphatase increased grade 1
         subjects affected / exposed
    12 / 81 (14.81%)
    15 / 85 (17.65%)
         occurrences all number
    12
    15
    Diarrhea grade 2
         subjects affected / exposed
    0 / 81 (0.00%)
    4 / 85 (4.71%)
         occurrences all number
    0
    4
    Hemoglobin increased grade 3
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Neutrophil count decreased grade 3
         subjects affected / exposed
    2 / 81 (2.47%)
    0 / 85 (0.00%)
         occurrences all number
    2
    0
    Neutrophil count decreased grade 2
         subjects affected / exposed
    7 / 81 (8.64%)
    5 / 85 (5.88%)
         occurrences all number
    7
    5
    Neutrophil count decreased grade 1
         subjects affected / exposed
    13 / 81 (16.05%)
    13 / 85 (15.29%)
         occurrences all number
    13
    13
    White blood cells decreased grade 2
         subjects affected / exposed
    7 / 81 (8.64%)
    5 / 85 (5.88%)
         occurrences all number
    7
    5
    White blood cells decreased grade 1
         subjects affected / exposed
    15 / 81 (18.52%)
    17 / 85 (20.00%)
         occurrences all number
    15
    17
    Cardiac disorders
    Heart failure grade 3
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Fatigue grade 3
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences all number
    0
    1
    Fatigue grade 2
         subjects affected / exposed
    3 / 81 (3.70%)
    5 / 85 (5.88%)
         occurrences all number
    3
    5
    Fatigue grade 1
         subjects affected / exposed
    10 / 81 (12.35%)
    16 / 85 (18.82%)
         occurrences all number
    10
    16
    Injection site reaction grade 2
         subjects affected / exposed
    2 / 81 (2.47%)
    3 / 85 (3.53%)
         occurrences all number
    2
    3
    Injection site reaction grade 1
         subjects affected / exposed
    9 / 81 (11.11%)
    6 / 85 (7.06%)
         occurrences all number
    9
    6
    Blood and lymphatic system disorders
    Anemia grade 2
         subjects affected / exposed
    5 / 81 (6.17%)
    2 / 85 (2.35%)
         occurrences all number
    5
    2
    Anemia grade 1
         subjects affected / exposed
    27 / 81 (33.33%)
    32 / 85 (37.65%)
         occurrences all number
    27
    32
    Reproductive system and breast disorders
    Nodule in left breast grade 3
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Diarrhea grade 3
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Diarrhea grade 1
         subjects affected / exposed
    6 / 81 (7.41%)
    5 / 85 (5.88%)
         occurrences all number
    6
    5
    Nausea grade 3
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Nausea grade 2
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Nausea grade 1
         subjects affected / exposed
    4 / 81 (4.94%)
    0 / 85 (0.00%)
         occurrences all number
    4
    0
    Vomiting grade 3
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Vomiting grade 2
         subjects affected / exposed
    2 / 81 (2.47%)
    0 / 85 (0.00%)
         occurrences all number
    2
    0
    Vomiting grade 1
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Voice alteration grade 3
         subjects affected / exposed
    1 / 81 (1.23%)
    0 / 85 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Osteonecrosis of jaw grade 3
         subjects affected / exposed
    0 / 81 (0.00%)
    1 / 85 (1.18%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Jul 2013
    The modification of the moment of blood draw of the first blood sample for participation in the optional immunogenicity study: As indicated in the protocol version 1 of October 19, 2012, this sample should be obtained within 14 days prior to the inclusion of the patient in the study. It is considered necessary to postpone this blood draw and perform it before the administration of the first cycle of subcutaneous trastuzumab, as it seems more appropriate than the blood draw of a sample for participation in an optional study is carried out once the patient has been included in the study, after all screening tests have been performed and all the selection criteria have been met. This also ensures that the sample is obtained at the same time for all patients. Errata correction and typographical errors.
    14 Feb 2014
    Immunogenicity sub-study has been eliminated due to it is not possible to carry out. To allow other immunotherapy, including humanized anti-HER2 antibodies, so it is possible to include patients under pertuzumab treatment (approved in combination with trastuzumab for first line). To change the obtaining date of the first questionnaire about the patient's experiences and preferences (C1), to be required after the randomization and before the administration of the first subcutaneous trastuzumab cycle (instead of within 14 days prior to the inclusion), because it is more appropriate for the patient to complete this specific study procedure once it has been included in the study. HER2 positive criteria have been updated according to the 2013 ASCO / CAP guidelines. Trastuzumab investigator brochure has been updated to version 14 of October 2013 To incorporate 19 sites in the study. Also typographical errors were corrected.
    31 Mar 2016
    The trastuzumab single-use injection device is no longer to be supplied in the study, because laboratory has decided to cease its manufacturing. The decision to discontinue SID manufacturing was not due to any SID safety or quality concerns. The device is one of the two subcutaneous (SC) formulations provided in this study and this fact does not impact in the supply of the other formulation, the SC trastuzumab with vial. This amendment includes also the sample size decrease (from 195 to 160 patients) based on the updated and published results on the preference rate of other study with SC vs IV trastuzumab (PrefHER). Administrative changes and grammatical mistakes were corrected

    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.
    We do not have longterm follow-up data of the SC-t efficacy. Device SC-t SID has not been commercialized. All patients had already been treated with IV-t for at least 4 months without disease progression prior to the study entry.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/32578279
    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-Sun Apr 28 18:33:11 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA