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   44364   clinical trials with a EudraCT protocol, of which   7388   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 II randomized trial comparing alpelisib and fulvestrant versus chemotherapy as maintenance therapy in patients with PIK3CA mutated advanced breast cancer

    Summary
    EudraCT number
    		 2017-000154-19
    Trial protocol
    		 FR  
    Global end of trial date
    18 Nov 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    UC-0105/1701
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03386162
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    UNICANCER
    Sponsor organisation address
    101 rue de Tolbiac, Paris, France, 75015
    Public contact
    Nourredine AIT-RAHMOUNE, UNICANCER, 33 0171936704, n.ait-rahmoune@unicancer.fr
    Scientific contact
    Nourredine AIT-RAHMOUNE, UNICANCER, 33 0171936704, n.ait-rahmoune@unicancer.fr
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Oct 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Jul 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Nov 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to maintenance chemotherapy in patients PIK3CA mutated with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who do not present a progressive disease after 6-8 cycles of chemotherapy.
    Protection of trial subjects
    This study was conducted in compliance with the protocol, in accordance with the French national regulatory requirements and the Declaration of Helsinki (1964) and subsequent amendments, ICH Good Clinical Practice (GCP) Guidelines (CPMP/ICH/135/95), the European Directive (2001/20/CE) and the applicable local regulatory requirements and laws.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Apr 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 24 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 31
    Worldwide total number of subjects
    31
    EEA total number of subjects
    31
    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)
    15
    From 65 to 84 years
    16
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 From 05-Apr-2018 to 03-Aug-2020, 31 patients were included and randomized in a 2:1 ratio across 14 centers. Thus, 20 and 11 patients were allocated to the experimental Arm A3 (alpelisib) and control Arm B3 (standard chemotherapy), respectively.

    Pre-assignment
    Screening details
    		 The main Inclusion criteria: - Women (or men) with histologically confirmed metastatic breast cancer - Hormone receptor positive (HR+) and no Her2 over-expression, according to local assessment. - Presence of PIK3CA mutation on exon 9 or 20, determined on metastatic tissue specimen (frozen or FFPE) or plasma (ctDNA).

    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
    		 Arm A3: alpelisib + fulvestrant +/- LH-RH analogs
    Arm description
    		 In the experimental Arm A3, patients were receiving: - Alpelisib 300 mg administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 21-day cycle, in combination with - fulvestrant 2x250 mg intra muscular every 28 days (+/- 3 days) starting on Cycle 1 Day 1 with an additional injection on Day 15 according to Summary of Product Characteristics (SmPC) conditions. - LH-RH agonists for premenopausal women only was administered every 28 days (+/- 3 days) according to SmPC conditions, starting on Cycle 1 Day 1. In Arm A3, a cycle was defined as a 21-day (± 2 days) period for alpelisib. Fulvestrant and/or LH-RH analogs were administered every 28 days independently from the 21-day cycles of alpelisib. The last day of a complete treatment cycle was Day 21. Day 1 of the next cycle started on Day 22.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Alpelisib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients received 300 mg once daily every day, starting at Day 1.

    Investigational medicinal product name
    Fulvestrant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    As per usual practice : 2x250 mg, every 28 days, starting at Day 1, with 1 additional injection of 2x250mg at D15 after the first injection.

    Investigational medicinal product name
    LH-RH agonits on the market: Goserelin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    As per usual practice : 3.6 mg every 28 days, starting at Day 1.

    Investigational medicinal product name
    LH-RH agonits on the market : Leuprorelin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    As per usual practice: 3.75 mg every 28 days, starting at Day 1.

    Arm title
    		 Arm B3: standard chemotherapy
    Arm description
    		 In the control Arm B3, patients were receiving: - Standard chemotherapy (at the investigator’s choice) continued as maintenance chemotherapy, or no antineoplastic treatment in case of toxicity. Maintenance chemotherapy agents had to be administered and dose reduced according to SmPC recommendations and local standard practice.
    Arm type
    		 Control arm

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Arm A3: alpelisib + fulvestrant +/- LH-RH analogs Arm B3: standard chemotherapy
    Started
    20
    11
    Completed
    1
    0
    Not completed
    19
    11
         Physician decision
    -
    2
         Adverse event
    5
    -
         RECIST progression
    13
    7
         Study drug not administred
    1
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Arm A3: alpelisib + fulvestrant +/- LH-RH analogs
    Reporting group description
    		 In the experimental Arm A3, patients were receiving: - Alpelisib 300 mg administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 21-day cycle, in combination with - fulvestrant 2x250 mg intra muscular every 28 days (+/- 3 days) starting on Cycle 1 Day 1 with an additional injection on Day 15 according to Summary of Product Characteristics (SmPC) conditions. - LH-RH agonists for premenopausal women only was administered every 28 days (+/- 3 days) according to SmPC conditions, starting on Cycle 1 Day 1. In Arm A3, a cycle was defined as a 21-day (± 2 days) period for alpelisib. Fulvestrant and/or LH-RH analogs were administered every 28 days independently from the 21-day cycles of alpelisib. The last day of a complete treatment cycle was Day 21. Day 1 of the next cycle started on Day 22.

    Reporting group title
    Arm B3: standard chemotherapy
    Reporting group description
    		 In the control Arm B3, patients were receiving: - Standard chemotherapy (at the investigator’s choice) continued as maintenance chemotherapy, or no antineoplastic treatment in case of toxicity. Maintenance chemotherapy agents had to be administered and dose reduced according to SmPC recommendations and local standard practice.

    Reporting group values
    		 Arm A3: alpelisib + fulvestrant +/- LH-RH analogs Arm B3: standard chemotherapy Total
    Number of subjects
    		 20 11 31
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 8 6 14
        From 65-84 years
    		 12 5 17
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 66.5 (34 to 75) 58 (41 to 74) -
    Gender categorical
    Units: Subjects
        Female
    		 18 11 29
        Male
    		 2 0 2
    Menopausal status
    Units: Subjects
        Non-menopausal
    		 3 1 4
        Post-menopausal
    		 15 10 25
        Na
    		 2 0 2
    ECOG performance status
    Units: Subjects
        ECOG 0
    		 11 5 16
        ECOG 1
    		 8 5 13
        Missing
    		 1 1 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arm A3: alpelisib + fulvestrant +/- LH-RH analogs
    Reporting group description
    		 In the experimental Arm A3, patients were receiving: - Alpelisib 300 mg administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 21-day cycle, in combination with - fulvestrant 2x250 mg intra muscular every 28 days (+/- 3 days) starting on Cycle 1 Day 1 with an additional injection on Day 15 according to Summary of Product Characteristics (SmPC) conditions. - LH-RH agonists for premenopausal women only was administered every 28 days (+/- 3 days) according to SmPC conditions, starting on Cycle 1 Day 1. In Arm A3, a cycle was defined as a 21-day (± 2 days) period for alpelisib. Fulvestrant and/or LH-RH analogs were administered every 28 days independently from the 21-day cycles of alpelisib. The last day of a complete treatment cycle was Day 21. Day 1 of the next cycle started on Day 22.

    Reporting group title
    Arm B3: standard chemotherapy
    Reporting group description
    		 In the control Arm B3, patients were receiving: - Standard chemotherapy (at the investigator’s choice) continued as maintenance chemotherapy, or no antineoplastic treatment in case of toxicity. Maintenance chemotherapy agents had to be administered and dose reduced according to SmPC recommendations and local standard practice.

    Primary: Progression-free survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-free survival (PFS)
    End point description
    The primary endpoint of the study was the PFS and was defined as the time from randomization to the first documented progression of disease or death, whatever the cause. The tumor assessments were made by the investigators based on RECIST 1.1 criteria. Patients still alive at the time of analysis without documented progression (including lost to follow-up) were censored at the last known alive date.
    End point type
    Primary
    End point timeframe
    Time from randomization to the first documented progression of disease or death, whatever the cause.
    End point values
    		 Arm A3: alpelisib + fulvestrant +/- LH-RH analogs Arm B3: standard chemotherapy
    Number of subjects analysed
    20
    11
    Units: Months
        median (confidence interval 95%)
    9.5 (3.5 to 13.3)
    8.0 (1.3 to 15.5)
    Statistical analysis title
    		 PFS analysis
    Comparison groups
    Arm A3: alpelisib + fulvestrant +/- LH-RH analogs v Arm B3: standard chemotherapy
    Number of subjects included in analysis
    31
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9769
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 2.4

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    The Overall Survival (OS) was the time from randomization to death due to any cause. Patients still alive at the time of analysis (including lost to follow-up) were censored at the last known alive date.
    End point type
    Secondary
    End point timeframe
    Time from randomization to death due to any cause.
    End point values
    		 Arm A3: alpelisib + fulvestrant +/- LH-RH analogs Arm B3: standard chemotherapy
    Number of subjects analysed
    20
    11
    Units: Patients
        Died
    12
    3
        Alive
    8
    8
    No statistical analyses for this end point

    Secondary: Objective response rate (ORR)

    		 Close Top of page
    End point title
    		 Objective response rate (ORR)
    End point description
    The objective response rate (ORR) was the percentage of patients with at least one tumor assessment demonstrating a complete response (CR) or partial response (PR) using RECIST v1.1 criteria. The tumor assessments after first progression or treatment switching was ignored.
    End point type
    Secondary
    End point timeframe
    Tumor response is assessed every 21 days from treatment initiation until first progression or death from any cause,
    End point values
    		 Arm A3: alpelisib + fulvestrant +/- LH-RH analogs Arm B3: standard chemotherapy
    Number of subjects analysed
    20
    11
    Units: percent
        number (not applicable)
    22.2
    25
    No statistical analyses for this end point

    Secondary: PFS sensitivity analysis

    		 Close Top of page
    End point title
    		 PFS sensitivity analysis
    End point description
    End point type
    Secondary
    End point timeframe
    Time from randomization to the first documented progression of disease or death, whatever the cause.
    End point values
    		 Arm A3: alpelisib + fulvestrant +/- LH-RH analogs Arm B3: standard chemotherapy
    Number of subjects analysed
    20
    11
    Units: Months
        median (confidence interval 95%)
    7.8 (4 to 13.3)
    8 (1.3 to 15.5)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from the date of the patient’s signing of the informed consent, during treatment, and during follow up.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Arm A3: alpelisib + fulvestrant +/- LH-RH analogs
    Reporting group description
    		 In the experimental Arm A3, patients were receiving: - Alpelisib 300 mg administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 21-day cycle, in combination with - fulvestrant 2x250 mg intra muscular every 28 days (+/- 3 days) starting on Cycle 1 Day 1 with an additional injection on Day 15 according to Summary of Product Characteristics (SmPC) conditions. - LH-RH agonists for premenopausal women only was administered every 28 days (+/- 3 days) according to SmPC conditions, starting on Cycle 1 Day 1. In Arm A3, a cycle was defined as a 21-day (± 2 days) period for alpelisib. Fulvestrant and/or LH-RH analogs were administered every 28 days independently from the 21-day cycles of alpelisib. The last day of a complete treatment cycle was Day 21. Day 1 of the next cycle started on Day 22.

    Reporting group title
    Arm B3: standard chemotherapy
    Reporting group description
    		 In the control Arm B3, patients were receiving: - Standard chemotherapy (at the investigator’s choice) continued as maintenance chemotherapy, or no antineoplastic treatment in case of toxicity. Maintenance chemotherapy agents had to be administered and dose reduced according to SmPC recommendations and local standard practice.

    Serious adverse events
    		 Arm A3: alpelisib + fulvestrant +/- LH-RH analogs Arm B3: standard chemotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 19 (26.32%)
    0 / 9 (0.00%)
         number of deaths (all causes)
    12
    2
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Electrocardiogram QT corrected interval prolonged
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Epileptic seizure
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Arm A3: alpelisib + fulvestrant +/- LH-RH analogs Arm B3: standard chemotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 19 (100.00%)
    8 / 9 (88.89%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    13
    0
    Hot Flush
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 9 (11.11%)
         occurrences all number
    4
    1
    Hypertension
         subjects affected / exposed
    4 / 19 (21.05%)
    0 / 9 (0.00%)
         occurrences all number
    13
    0
    Lymphedema
         subjects affected / exposed
    4 / 19 (21.05%)
    0 / 9 (0.00%)
         occurrences all number
    18
    0
    Vein disorder
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    6
    0
    Venous thrombosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    15
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    10 / 19 (52.63%)
    5 / 9 (55.56%)
         occurrences all number
    38
    31
    Fatigue
         subjects affected / exposed
    6 / 19 (31.58%)
    1 / 9 (11.11%)
         occurrences all number
    54
    8
    Mucosal Inflammation
         subjects affected / exposed
    3 / 19 (15.79%)
    0 / 9 (0.00%)
         occurrences all number
    8
    0
    General physical health deterioration
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Edema
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Reproductive system and breast disorders
    Breast Pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    5
    0
    Nipple Exudate Bloody
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Vaginal Hemorrhage
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Vulvovaginal Dryness
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    6
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Dyspnea
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 9 (11.11%)
         occurrences all number
    1
    2
    Epistaxis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Rhinorrhea
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 9 (11.11%)
         occurrences all number
    4
    7
    Confusional State
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Depression
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    7
    0
    Insomnia
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    7
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 9 (11.11%)
         occurrences all number
    1
    3
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 9 (11.11%)
         occurrences all number
    2
    3
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    3
    Blood Bilirubin Increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Blood Creatine Phosphokinase Increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Blood Creatinine Increased
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    9
    0
    Creatinine Renal Clearance Decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Electrocardiogram Qt Prolonged
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Insulin C-Peptide Increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Lipase Increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Weight Decreased
         subjects affected / exposed
    3 / 19 (15.79%)
    0 / 9 (0.00%)
         occurrences all number
    11
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Pericarditis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Balance disorder
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Dysgeusia
         subjects affected / exposed
    4 / 19 (21.05%)
    0 / 9 (0.00%)
         occurrences all number
    17
    0
    Epilepsy
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    3 / 19 (15.79%)
    1 / 9 (11.11%)
         occurrences all number
    9
    1
    Hepatic Encephalopathy
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Memory impairment
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 9 (22.22%)
         occurrences all number
    13
    4
    Paresthesia
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 9 (11.11%)
         occurrences all number
    3
    5
    Peripheral Motor Neuropathy
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    6
    0
    Sciatica
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    4 / 19 (21.05%)
    0 / 9 (0.00%)
         occurrences all number
    9
    0
    Lymphopenia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Neutropenia
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 9 (22.22%)
         occurrences all number
    1
    2
    Thrombocytopenia
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 9 (11.11%)
         occurrences all number
    5
    1
    Eczema eyelids
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Lacrimation Increased
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Retinal disorder
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Visual Impairment
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal Distension
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Abdominal Pain
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 9 (11.11%)
         occurrences all number
    7
    3
    Abdominal Pain Upper
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 9 (11.11%)
         occurrences all number
    4
    2
    Aphthous Ulcer
         subjects affected / exposed
    3 / 19 (15.79%)
    0 / 9 (0.00%)
         occurrences all number
    9
    0
    Constipation
         subjects affected / exposed
    5 / 19 (26.32%)
    1 / 9 (11.11%)
         occurrences all number
    6
    3
    Diarrhoea
         subjects affected / exposed
    14 / 19 (73.68%)
    5 / 9 (55.56%)
         occurrences all number
    107
    25
    Dry mouth
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    5
    0
    Dyspepsia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Gastroesophageal Reflux Disease
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Hemorrhoids
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Mouth Ulceration
         subjects affected / exposed
    3 / 19 (15.79%)
    0 / 9 (0.00%)
         occurrences all number
    6
    0
    Nausea
         subjects affected / exposed
    9 / 19 (47.37%)
    4 / 9 (44.44%)
         occurrences all number
    32
    11
    Esophagitis
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Stomatitis
         subjects affected / exposed
    4 / 19 (21.05%)
    0 / 9 (0.00%)
         occurrences all number
    7
    0
    Vomiting
         subjects affected / exposed
    5 / 19 (26.32%)
    0 / 9 (0.00%)
         occurrences all number
    7
    0
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    4
    0
    Hepatic Cytolysis
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    4 / 19 (21.05%)
    1 / 9 (11.11%)
         occurrences all number
    30
    2
    Dermatitis Acneiform
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    5
    0
    Digital Pulpitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Dry skin
         subjects affected / exposed
    3 / 19 (15.79%)
    0 / 9 (0.00%)
         occurrences all number
    27
    0
    Eczema
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Erythema
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Livedo Reticularis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Mucocutaneous Rash
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Nail Disorder
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 9 (33.33%)
         occurrences all number
    8
    31
    Palmar-Plantar Erythrodysaesthesia Syndrome
         subjects affected / exposed
    3 / 19 (15.79%)
    3 / 9 (33.33%)
         occurrences all number
    14
    49
    Panniculitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    5
    0
    Photosensitivity Reaction
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Plantar Erythema
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    4
    0
    Rash
         subjects affected / exposed
    5 / 19 (26.32%)
    1 / 9 (11.11%)
         occurrences all number
    8
    1
    Skin Hemorrhage
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Skin lesion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    4
    0
    Subcutaneous Abscess
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Xeroderma
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Renal Failure
         subjects affected / exposed
    4 / 19 (21.05%)
    0 / 9 (0.00%)
         occurrences all number
    14
    0
    Endocrine disorders
    Adrenal Hemorrhage
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    10
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 19 (26.32%)
    2 / 9 (22.22%)
         occurrences all number
    22
    4
    Back Pain
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 9 (22.22%)
         occurrences all number
    8
    3
    Muscle Spasms
         subjects affected / exposed
    6 / 19 (31.58%)
    0 / 9 (0.00%)
         occurrences all number
    25
    0
    Muscular weakness
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Musculoskeletal Chest Pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 9 (11.11%)
         occurrences all number
    2
    2
    Neck Pain
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Cystitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Dermo-Hypodermitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Ear infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Fungal infection
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Localized Infection
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    3
    Nail Infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Paronychia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    4
    0
    Pneumonia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Rash pustular
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Respiratory Tract Infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Tooth abscess
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Urinary Tract Infection
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 9 (0.00%)
         occurrences all number
    6
    0
    Metabolism and nutrition disorders
    Cell Death
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Decreased Appetite
         subjects affected / exposed
    10 / 19 (52.63%)
    0 / 9 (0.00%)
         occurrences all number
    52
    0
    Diabetes Mellitus
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    4
    0
    Hyperglycemia
         subjects affected / exposed
    12 / 19 (63.16%)
    0 / 9 (0.00%)
         occurrences all number
    94
    0
    Hyperkalemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Hyperuricemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Hypoglycemia
         subjects affected / exposed
    3 / 19 (15.79%)
    0 / 9 (0.00%)
         occurrences all number
    4
    0
    Hypokalemia
         subjects affected / exposed
    3 / 19 (15.79%)
    0 / 9 (0.00%)
         occurrences all number
    12
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Dec 2017
    - Modification of the investigators list
    09 Feb 2018
    - Modification of the investigators list
    05 Apr 2018
    - Modification of the investigators list
    20 Jun 2019
    - Modification of the study protocol: 1- Following national recommendations update, inclusion criteria N°27 (uracilemia < 16 ng/ml) was added to prevent severe or fatal toxicities in patients having a partial or total enzyme deficiency in dihydropyrimidine dehydrogenase (DPD) 2- Addition of a blood sample collection for the ancillary study on ctDNA - Updated version of the alpelisib (BYL719) investigator brochure (Version 10, 12-Jul-2017 and Version 11, 05-Jul-2018) with impact on the safety patients and/or protocol: 1- A second Stevenson Johnson Syndrome case and 2 new cases of erythema multiform had been reported. 2- Several adverse reactions already described had a frequency changed (dry mouth, vertigo, and nail loss). The informed consent form had been updated. Patient care and follow-up remained appropriate and unchanged in protocol 3- Two cases of anaphylactic shock were reported as probably related to alpelisib treatment in combination studies (one with ribociclib and one with cetuximab). The risk of anaphylactic shock was classified as uncommon and had been added to the informed consent form. Patient care and follow-up remained appropriate and unchanged in protocol 4- Three cases of increased lipase levels were added as likely related to alpelisib treatment in combination studies with cetuximab, AUY922 (Novartis) or fulvestrant. 5-The section on severe skin reactions had been updated to reinforce the management of these toxicities and the protocol was updated with these new instructions 6- Addition of contraceptive methods, preclinical studies in rats and rabbits, and hepatic disturbances were added to the IB. Protocol was not updated - Modification of the of the informed consent form: compliance with the new data protection regulation - Modification of the investigators list
    11 Mar 2020
    - Modification of the study protocol to extend the inclusion period by 15 months (from 30 months to 45 months) - Updated version of the alpelisib (BYL719) investigator brochure (Version 12, 26-Jul-2019 and Version 13, 10-Oct-2019) with impact on the safety patients and/or protocol: 1- In the version 12, a single table reporting the expected severe adverse reactions with alpelisib and fulvestrant was added: - One severe adverse reaction, osteonecrosis of the jaw, was added - Some severe adverse reactions described in previous version were not mentioned anymore - Some severe expected adverse reactions changed in frequency (i.e. acute renal failure changed from uncommon to common) - New adverse events were described 2- In the version 13, a new potential reaction was added; drug hypersensitivity syndrome (DRESS). - Modification of the study protocol: - Addition of osteonecrosis of the jaw in the safety section and non-inclusion criteria N°28. Patient care and follow-up remained appropriate and unchanged in protocol - Addition of DRESS in the safety section. Patient care and follow-up remained appropriate and unchanged in protocol - Modification of the informed consent form consistent with the BI updates - Modification of the investigators list
    27 Jun 2022
    - On the 03-Aug-2020, the sponsor and the co-investigator conjointly decided to an early and permanently stop of patients inclusions in the study. The decision was based on the low recruitment noticed on Aug-2020, with only 31 patients mutated in the PI3K gene included out of the 90 patients expected in 30 months. The end of the SAFIR02 Breast molecular screening study (2013-001652-36), which until then had made it possible to identify anomalies of the PI3KCA gene, had make it more difficult to reach the objective of 90 patients included. Two patients in the Arm A3 (alpelisib) were still under treatment and completed the study as planned in the protocol. The IEC and the AC were notified by letter on the 10-Aug-2020 and 13-Sep-2021, respectively. - On the 21-Jul-2022, no patients were currently taken alpelisib treatment and nine patients were in post-treatment follow-up. It was no longer necessary to collect long-term follow-up data as the study could not be analyzed based on its endpoints. The early and definitive termination of all patients monitoring in the SAFIR-PI3K study was notified by letter on the 27-Jun-2022 to the IEC and the ANSM.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    03 Aug 2020
    The sponsor and the co-investigator conjointly decided to an early and permanently stop of patients inclusions in the study. The decision was based on the low recruitment noticed on Aug-2020, with only 31 patients mutated in the PI3K gene included out of the 90 patients expected in 30 months. The end of the SAFIR02 Breast molecular screening study (2013-001652-36), which until then had made it possible to identify anomalies of the PI3KCA gene, had make it more difficult to reach the objective of 90 patients included. Two patients in the Arm A3 (alpelisib) were still under treatment and completed the study as planned in the protocol. The IEC and the AC were notified by letter on the 10-Aug-2020 and 13-Sep-2021, respectively.
    -

    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-Sat Oct 25 07:07:29 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA