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SOLAR-1: Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02437318
Collaborator
(none)
572
Enrollment
197
Locations
2
Arms
94.5
Anticipated Duration (Months)
2.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who received prior treatment with an Aromatase Inhibitor either as (neo)adjuvant or for advanced disease.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
572 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized Double-blind, Placebo Controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment
Actual Study Start Date :
Jul 23, 2015
Actual Primary Completion Date :
Jun 12, 2018
Anticipated Study Completion Date :
Jun 8, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: fulvestrant + alpelisib

Alpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)

Drug: Fulvestrant
Other Names:
  • Faslodex

    • Drug: Alpelisib
    Placebo Comparator: fulvestrant + placebo

    Placebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)

    Drug: Fulvestrant
    Other Names:
  • Faslodex

    • Drug: Alpelisib placebo

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort [Once approximately 243 PFS events in this cohort had been observed, up to 32 months]

      PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1

    Secondary Outcome Measures

    1. Overall Survival (OS) for Patients With PI3KCA Mutant Status [Up to approximatly 59 months]

      OS is defined as the time from date of randomization to date of death due to any cause.

    2. Overall Response Rate (ORR) [Up to approximatly 36 months]

      ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1.

    3. Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status [Baseline, Up to approximatly 36 months]

      Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

    4. Safety and Tolerability of Alpelisib in Combination With Fulvestrant [Up to approximatly 37 months]

      Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.

    5. Time to 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 [Up to approximatly 36 months]

      Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized

    6. Plasma Concentration-time Profile of Alpelisib Given in Combinatio With Fulvestrant and Appropriate Pharmacokinetics (PK) Parameters [Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8]

      Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples. PK parameters includes,but not limited to, Cmin, Cmax, t1/2, AUClast for alpelisib (and any relevant metabolites) and fulvestrant

    7. PFS Based on Radiology Assessments and Using RECIST 1.1 Criteria [Baseline, Up to approximatly 36 months]

      PFS in patients with PIK3CA mutant status and patients with PIK3CA non-mutant status as measured in ctDNA.

    8. Clinical Benefit Rate (CBR) [Up to approximatly 36 months]

      Clinical benefit rate is defined as the proportion of patients with a best overall response of CR or PR or SD or Non-CR/Non-PD lasting more than 24 weeks based on local investigator assessment.

    9. Change in the Global Health Status/(QOL) Scale Score of the EORTC QLQ-C30 [Baseline, Up to approximatly 36 months]

      Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized

    10. Summary Statistics of Fulvestrant and Alpelisib Plasma Concentrations [Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8]

      Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples.

    11. PFS for Patients With PIK3CA Non-mutant Status [Up to approximatly 36 months]

      PFS based on local radiology assessments and using RECIST 1.1 criteria in the PIK3CA non-mutant cohort

    12. OS for Patients With PIK3CA Non-mutant Status [Up to approximatly 59 months]

      OS is defined as the time from date of randomization to date of death due to any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • If female, patient is postmenopausal

    • Patient has identified PIK3CA status

    • Patients may be:

    • relapsed with documented evidence of progression while on (neo) adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease;

    • relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently; progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease;

    • newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy

    • Patient has recurrence or progression of disease during or after AI therapy (i.e.

    letrozole, anastrozole, exemestane).

    • Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by local laboratory and has HER2 negative breast cancer

    • Patient has either measurable disease per RECIST 1.1 criteria OR at least one predominantly lytic bone lesion must be present

    • Patient has adequate bone marrow function

    Exclusion Criteria:

    • Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment

    • Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor (pre-treatment with CDK4/6 inhibitors is allowed)

    • Patient with inflammatory breast cancer at screening

    • Patients with Child pugh score B or C

    • Patients with an established diagnosis of diabetes mellitus type I or not controlled type II

    • Patient has Eastern Cooperative Oncology Group (ECOG) performance status 2 or more

    • Patient with CNS involvement unless he/she is at least 4 weeks from prior therapy completion to starting the study treatment and has stable CNS tumor at time of screening and not receiving steroids and/or enzyme inducing ant-epileptic medications for brain metastases

    • Patient has participated in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer

    • Patient has a history of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis

    • Patient who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease

    Other protocol-defined inclusion/esclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ironwood Cancer and Research Centers Chandler 2 Chandler Arizona United States 85224
    2 Mayo Clinic - Arizona Scottsdale Arizona United States 85259
    3 Highlands Oncology Group Fayetteville Arkansas United States 72703
    4 Beverly Hills Cancer Center Beverly Hills California United States 90211
    5 City of Hope National Medical Center Duarte California United States 91010 3000
    6 Scripps Clinic SC La Jolla California United States 92037
    7 Kaiser Permanente - California Southern San Diego California United States 92120
    8 University of California San Francisco San Francisco California United States 94115
    9 Florida Cancer Specialists FL Cancer Specialists Fort Myers Florida United States 33901
    10 Florida Cancer Specialists-North SC Saint Petersburg Florida United States 33705
    11 Rush University Medical Center Rush Uni Medical Center Chicago Illinois United States 60612
    12 North Shore University Health System NorthShore University Evanston Illinois United States 60201
    13 Edward Cancer Center SC Naperville Illinois United States 60540
    14 Fort Wayne Medical Oncology/Hematology, Inc. Dept.of Fort Wayne Med Onc/Hem Fort Wayne Indiana United States 46815
    15 St. Francis Health Comprehensive Cancer Center SC Topeka Kansas United States 66606-169
    16 Mercy Medical Center SC-2 Baltimore Maryland United States 21202
    17 Massachusetts General Hospital Updated Regulatory Boston Massachusetts United States 02114
    18 Lahey Clinic Burlington Massachusetts United States 01805
    19 Detroit Clinical Research Center Owosso Michigan United States 48867
    20 St. Luke's Cancer Institute SC Kansas City Missouri United States 64111
    21 St Vincent Frontier Cancer Center Billings Montana United States 59102
    22 Rutgers Cancer Institute of New Jersey SC-2 New Brunswick New Jersey United States 08903
    23 University Hospitals of Cleveland Seidman Cancer Center SC Cleveland Ohio United States 44106
    24 Good Samaritan Regional Medical Center Good Samaritan Reg Med Ctr Corvallis Oregon United States 97330
    25 Lancaster General Hospital Lancaster Pennsylvania United States 17604
    26 Prisma Health Upstate SC-2 Greenville South Carolina United States 29615
    27 Avera Cancer SC Sioux Falls South Dakota United States 57105
    28 Tennessee Oncology SC-3 Nashville Tennessee United States 37203
    29 Texas Oncology PA Dallas Presbyterian Hospital SC-1 Dallas Texas United States 75231
    30 El Paso, Texas Oncology El Paso Texas United States 79902
    31 Cancer Therapy and Research Center UT Health Science Center InstituteForDrugDevelopment(4) San Antonio Texas United States 78229
    32 Texas Oncology Northeast Texas Tyler Texas United States 75702
    33 Virginia Cancer Specialists SC Fairfax Virginia United States 22031
    34 Wenatchee Valley Medical Center SC-2 Wenatchee Washington United States 98801
    35 Novartis Investigative Site Berazategui Buenos Aires Argentina B1884BBF
    36 Novartis Investigative Site Caba Buenos Aires Argentina C1125ABD
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    41 Novartis Investigative Site Elizabeth Vale South Australia Australia 5112
    42 Novartis Investigative Site Melbourne Victoria Australia 3000
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    46 Novartis Investigative Site Jette Brussel Belgium 1090
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    48 Novartis Investigative Site Bruxelles Belgium 1000
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    174 Novartis Investigative Site Castellon Comunidad Valenciana Spain 12002
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    188 Novartis Investigative Site Gavle Sweden SE-801 87
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    190 Novartis Investigative Site Vasteras Sweden 721 89
    191 Novartis Investigative Site Taipei Taiwan 10002
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    193 Novartis Investigative Site Bangkok THA Thailand 10330
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    195 Novartis Investigative Site Plymouth Devon United Kingdom PL6 8DH
    196 Novartis Investigative Site Leicester United Kingdom LE1 5WW
    197 Novartis Investigative Site London United Kingdom SE1 9RT

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02437318
    Other Study ID Numbers:
    • CBYL719C2301
    • 2015-000340-42
    First Posted:
    May 7, 2015
    Last Update Posted:
    Aug 10, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    BYL719
    HR+
    HER2-negative
    advanced breast cancer
    alpelisib
    fulvestrant
    PI3K
    Phase III
    ER+
    PgR+
    men
    postmenopausal
    aromatase inhibitor
    neoplasms
    Additional relevant MeSH terms:
    Breast Neoplasms
    Fulvestrant

    Study Results

    Participant Flow

    Recruitment Details A total of 340 subjects were planned for the PIK3CA mutant cohort and 341 were analyzed. A total of 220 subjects were planned for the PIK3CA non-mutant cohort and 231 were analyzed.
    Pre-assignment Detail
    Arm/Group Title Alpelisib qd + Fulvestrant Placebo qd + Fulvestrant
    Arm/Group Description Alpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle) Placebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)
    Period Title: Overall Study
    STARTED 284 288
    End of Treatment (Didn't Complete) 229 241
    Untreated (Protocol Deviation) 0 1
    COMPLETED 55 46
    NOT COMPLETED 229 242

    Baseline Characteristics

    Arm/Group Title Alpelisib qd + Fulvestrant Placebo qd + Fulvestrant Total
    Arm/Group Description Alpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle) Placebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle) Total of all reporting groups
    Overall Participants 284 288 572
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    62.6
    (9.74)
    63.3
    (10.26)
    63.0
    (10.00)
    Sex: Female, Male (Count of Participants)
    Female
    283
    99.6%
    288
    100%
    571
    99.8%
    Male
    1
    0.4%
    0
    0%
    1
    0.2%
    Race/Ethnicity, Customized (Number) [Number]
    White
    199
    70.1%
    178
    61.8%
    377
    65.9%
    Asian
    59
    20.8%
    66
    22.9%
    125
    21.9%
    Unknown
    14
    4.9%
    17
    5.9%
    31
    5.4%
    Other
    9
    3.2%
    17
    5.9%
    26
    4.5%
    Black or African American
    2
    0.7%
    6
    2.1%
    8
    1.4%
    American Indian or Alaska
    1
    0.4%
    4
    1.4%
    5
    0.9%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort
    Description PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1
    Time Frame Once approximately 243 PFS events in this cohort had been observed, up to 32 months

    Outcome Measure Data

    Analysis Population Description
    The Full analysis set (FAS) comprised of all subjects who were randomized to study treatment (alpelisib plus fulvestrant or matching placebo plus fulvestrant). Analysis comprised all subjects in the FAS with a PIK3CA mutation who were randomized to study treatment.
    Arm/Group Title Alpelisib qd + Fulvestrant Placebo qd + Fulvestrant
    Arm/Group Description Alpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle) Placebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)
    Measure Participants 169 172
    Median (95% Confidence Interval) [Months]
    11.0
    5.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Alpelisib qd + Fulvestrant, Placebo qd + Fulvestrant
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.00065
    Comments (one-sided)
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.65
    Confidence Interval (2-Sided) 95%
    0.50 to 0.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Overall Survival (OS) for Patients With PI3KCA Mutant Status
    Description OS is defined as the time from date of randomization to date of death due to any cause.
    Time Frame Up to approximatly 59 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    Title Overall Response Rate (ORR)
    Description ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1.
    Time Frame Up to approximatly 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    Title Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status
    Description Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
    Time Frame Baseline, Up to approximatly 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    Title Safety and Tolerability of Alpelisib in Combination With Fulvestrant
    Description Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.
    Time Frame Up to approximatly 37 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    Title Time to 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30
    Description Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized
    Time Frame Up to approximatly 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    Title Plasma Concentration-time Profile of Alpelisib Given in Combinatio With Fulvestrant and Appropriate Pharmacokinetics (PK) Parameters
    Description Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples. PK parameters includes,but not limited to, Cmin, Cmax, t1/2, AUClast for alpelisib (and any relevant metabolites) and fulvestrant
    Time Frame Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    Title PFS Based on Radiology Assessments and Using RECIST 1.1 Criteria
    Description PFS in patients with PIK3CA mutant status and patients with PIK3CA non-mutant status as measured in ctDNA.
    Time Frame Baseline, Up to approximatly 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Secondary Outcome
    Title Clinical Benefit Rate (CBR)
    Description Clinical benefit rate is defined as the proportion of patients with a best overall response of CR or PR or SD or Non-CR/Non-PD lasting more than 24 weeks based on local investigator assessment.
    Time Frame Up to approximatly 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    10. Secondary Outcome
    Title Change in the Global Health Status/(QOL) Scale Score of the EORTC QLQ-C30
    Description Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized
    Time Frame Baseline, Up to approximatly 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    11. Secondary Outcome
    Title Summary Statistics of Fulvestrant and Alpelisib Plasma Concentrations
    Description Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples.
    Time Frame Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    12. Secondary Outcome
    Title PFS for Patients With PIK3CA Non-mutant Status
    Description PFS based on local radiology assessments and using RECIST 1.1 criteria in the PIK3CA non-mutant cohort
    Time Frame Up to approximatly 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    13. Secondary Outcome
    Title OS for Patients With PIK3CA Non-mutant Status
    Description OS is defined as the time from date of randomization to date of death due to any cause.
    Time Frame Up to approximatly 59 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame Adverse Events and Serious Adverse Events were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 30.8 months.
    Adverse Event Reporting Description
    Arm/Group Title Alpelisib qd + Fulvestrant Placebo qd + Fulvestrant
    Arm/Group Description Alpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle) Placebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)
    All Cause Mortality
    Alpelisib qd + Fulvestrant Placebo qd + Fulvestrant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/284 (2.5%) 12/287 (4.2%)
    Serious Adverse Events
    Alpelisib qd + Fulvestrant Placebo qd + Fulvestrant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 99/284 (34.9%) 48/287 (16.7%)
    Blood and lymphatic system disorders
    Anaemia 5/284 (1.8%) 0/287 (0%)
    Febrile neutropenia 1/284 (0.4%) 0/287 (0%)
    Thrombotic microangiopathy 1/284 (0.4%) 0/287 (0%)
    Cardiac disorders
    Atrial fibrillation 0/284 (0%) 1/287 (0.3%)
    Cardiac arrest 1/284 (0.4%) 0/287 (0%)
    Cardiac failure 0/284 (0%) 2/287 (0.7%)
    Myocardial infarction 0/284 (0%) 1/287 (0.3%)
    Pericardial effusion 0/284 (0%) 1/287 (0.3%)
    Sinus tachycardia 0/284 (0%) 1/287 (0.3%)
    Gastrointestinal disorders
    Abdominal pain 6/284 (2.1%) 2/287 (0.7%)
    Colitis 0/284 (0%) 1/287 (0.3%)
    Constipation 0/284 (0%) 1/287 (0.3%)
    Diarrhoea 8/284 (2.8%) 0/287 (0%)
    Dyspepsia 1/284 (0.4%) 0/287 (0%)
    Enterocolitis 1/284 (0.4%) 0/287 (0%)
    Gallstone ileus 0/284 (0%) 1/287 (0.3%)
    Gastrointestinal haemorrhage 0/284 (0%) 1/287 (0.3%)
    Ileus 1/284 (0.4%) 0/287 (0%)
    Intestinal obstruction 1/284 (0.4%) 0/287 (0%)
    Melaena 1/284 (0.4%) 0/287 (0%)
    Nausea 5/284 (1.8%) 2/287 (0.7%)
    Oesophagitis 1/284 (0.4%) 0/287 (0%)
    Pancreatitis 1/284 (0.4%) 0/287 (0%)
    Stomatitis 4/284 (1.4%) 0/287 (0%)
    Subileus 0/284 (0%) 1/287 (0.3%)
    Upper gastrointestinal haemorrhage 2/284 (0.7%) 0/287 (0%)
    Vomiting 5/284 (1.8%) 3/287 (1%)
    General disorders
    Asthenia 1/284 (0.4%) 0/287 (0%)
    Chest pain 1/284 (0.4%) 0/287 (0%)
    Fatigue 1/284 (0.4%) 0/287 (0%)
    General physical health deterioration 2/284 (0.7%) 0/287 (0%)
    Malaise 1/284 (0.4%) 0/287 (0%)
    Mucosal inflammation 3/284 (1.1%) 0/287 (0%)
    Multiple organ dysfunction syndrome 1/284 (0.4%) 0/287 (0%)
    Pyrexia 4/284 (1.4%) 0/287 (0%)
    Hepatobiliary disorders
    Hepatic failure 1/284 (0.4%) 0/287 (0%)
    Hepatitis acute 1/284 (0.4%) 0/287 (0%)
    Immune system disorders
    Hypersensitivity 3/284 (1.1%) 0/287 (0%)
    Infections and infestations
    Abscess jaw 1/284 (0.4%) 0/287 (0%)
    Appendicitis 0/284 (0%) 1/287 (0.3%)
    Bacteraemia 1/284 (0.4%) 0/287 (0%)
    Cellulitis 2/284 (0.7%) 2/287 (0.7%)
    Erysipelas 1/284 (0.4%) 0/287 (0%)
    Herpes zoster 1/284 (0.4%) 0/287 (0%)
    Mediastinitis 0/284 (0%) 1/287 (0.3%)
    Peritonsillar abscess 1/284 (0.4%) 0/287 (0%)
    Pneumonia 3/284 (1.1%) 5/287 (1.7%)
    Pulmonary tuberculosis 0/284 (0%) 1/287 (0.3%)
    Pyelonephritis 0/284 (0%) 1/287 (0.3%)
    Pyelonephritis acute 1/284 (0.4%) 0/287 (0%)
    Respiratory tract infection 0/284 (0%) 1/287 (0.3%)
    Septic shock 0/284 (0%) 1/287 (0.3%)
    Skin infection 0/284 (0%) 1/287 (0.3%)
    Urinary tract infection 2/284 (0.7%) 3/287 (1%)
    Urosepsis 1/284 (0.4%) 0/287 (0%)
    Injury, poisoning and procedural complications
    Femur fracture 0/284 (0%) 1/287 (0.3%)
    Hip fracture 1/284 (0.4%) 1/287 (0.3%)
    Overdose 0/284 (0%) 1/287 (0.3%)
    Procedural complication 0/284 (0%) 1/287 (0.3%)
    Radiation proctitis 1/284 (0.4%) 0/287 (0%)
    Rib fracture 1/284 (0.4%) 0/287 (0%)
    Spinal compression fracture 1/284 (0.4%) 1/287 (0.3%)
    Ulna fracture 0/284 (0%) 1/287 (0.3%)
    Wrist fracture 1/284 (0.4%) 0/287 (0%)
    Investigations
    Blood bilirubin increased 0/284 (0%) 1/287 (0.3%)
    Blood creatinine increased 2/284 (0.7%) 0/287 (0%)
    Haemoglobin decreased 1/284 (0.4%) 0/287 (0%)
    Hepatic enzyme increased 1/284 (0.4%) 0/287 (0%)
    Lipase increased 1/284 (0.4%) 0/287 (0%)
    Weight decreased 1/284 (0.4%) 0/287 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 2/284 (0.7%) 0/287 (0%)
    Dehydration 3/284 (1.1%) 3/287 (1%)
    Diabetic ketoacidosis 1/284 (0.4%) 0/287 (0%)
    Hypercalcaemia 0/284 (0%) 2/287 (0.7%)
    Hyperglycaemia 28/284 (9.9%) 0/287 (0%)
    Hypochloraemia 1/284 (0.4%) 0/287 (0%)
    Hypokalaemia 3/284 (1.1%) 1/287 (0.3%)
    Hyponatraemia 2/284 (0.7%) 1/287 (0.3%)
    Ketoacidosis 1/284 (0.4%) 0/287 (0%)
    Type 2 diabetes mellitus 1/284 (0.4%) 0/287 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 2/284 (0.7%) 2/287 (0.7%)
    Bone pain 0/284 (0%) 1/287 (0.3%)
    Muscular weakness 2/284 (0.7%) 0/287 (0%)
    Musculoskeletal chest pain 1/284 (0.4%) 0/287 (0%)
    Osteitis 0/284 (0%) 1/287 (0.3%)
    Osteonecrosis of jaw 5/284 (1.8%) 1/287 (0.3%)
    Spinal column stenosis 1/284 (0.4%) 0/287 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/284 (0%) 1/287 (0.3%)
    Metastases to meninges 1/284 (0.4%) 0/287 (0%)
    Second primary malignancy 1/284 (0.4%) 0/287 (0%)
    Tumour pain 1/284 (0.4%) 0/287 (0%)
    Nervous system disorders
    Altered state of consciousness 0/284 (0%) 1/287 (0.3%)
    Brain oedema 2/284 (0.7%) 0/287 (0%)
    Cerebrovascular accident 0/284 (0%) 1/287 (0.3%)
    Headache 1/284 (0.4%) 0/287 (0%)
    Motor dysfunction 0/284 (0%) 1/287 (0.3%)
    Seizure 1/284 (0.4%) 0/287 (0%)
    Spinal cord compression 0/284 (0%) 2/287 (0.7%)
    Syncope 1/284 (0.4%) 0/287 (0%)
    Psychiatric disorders
    Bipolar disorder 1/284 (0.4%) 0/287 (0%)
    Renal and urinary disorders
    Acute kidney injury 5/284 (1.8%) 1/287 (0.3%)
    Nephrolithiasis 1/284 (0.4%) 1/287 (0.3%)
    Renal failure 2/284 (0.7%) 0/287 (0%)
    Ureterolithiasis 1/284 (0.4%) 0/287 (0%)
    Reproductive system and breast disorders
    Pelvic pain 0/284 (0%) 1/287 (0.3%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/284 (0%) 1/287 (0.3%)
    Aspiration 0/284 (0%) 1/287 (0.3%)
    Bronchostenosis 0/284 (0%) 1/287 (0.3%)
    Dyspnoea 2/284 (0.7%) 4/287 (1.4%)
    Interstitial lung disease 1/284 (0.4%) 1/287 (0.3%)
    Pleural effusion 3/284 (1.1%) 5/287 (1.7%)
    Pneumonitis 2/284 (0.7%) 0/287 (0%)
    Pulmonary embolism 2/284 (0.7%) 3/287 (1%)
    Pulmonary oedema 1/284 (0.4%) 0/287 (0%)
    Respiratory failure 1/284 (0.4%) 0/287 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform 1/284 (0.4%) 0/287 (0%)
    Dermatitis allergic 1/284 (0.4%) 0/287 (0%)
    Erythema 1/284 (0.4%) 0/287 (0%)
    Erythema multiforme 3/284 (1.1%) 0/287 (0%)
    Rash 5/284 (1.8%) 0/287 (0%)
    Rash generalised 1/284 (0.4%) 0/287 (0%)
    Rash macular 1/284 (0.4%) 0/287 (0%)
    Rash maculo-papular 3/284 (1.1%) 0/287 (0%)
    Stevens-Johnson syndrome 1/284 (0.4%) 0/287 (0%)
    Urticaria 1/284 (0.4%) 0/287 (0%)
    Vascular disorders
    Hypertension 1/284 (0.4%) 0/287 (0%)
    Hypertensive crisis 1/284 (0.4%) 0/287 (0%)
    Thrombosis 0/284 (0%) 1/287 (0.3%)
    Other (Not Including Serious) Adverse Events
    Alpelisib qd + Fulvestrant Placebo qd + Fulvestrant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 279/284 (98.2%) 243/287 (84.7%)
    Blood and lymphatic system disorders
    Anaemia 22/284 (7.7%) 14/287 (4.9%)
    Gastrointestinal disorders
    Abdominal pain 30/284 (10.6%) 19/287 (6.6%)
    Abdominal pain upper 16/284 (5.6%) 11/287 (3.8%)
    Constipation 22/284 (7.7%) 36/287 (12.5%)
    Diarrhoea 161/284 (56.7%) 45/287 (15.7%)
    Dry mouth 27/284 (9.5%) 12/287 (4.2%)
    Dyspepsia 31/284 (10.9%) 16/287 (5.6%)
    Nausea 127/284 (44.7%) 63/287 (22%)
    Stomatitis 68/284 (23.9%) 18/287 (6.3%)
    Vomiting 73/284 (25.7%) 26/287 (9.1%)
    General disorders
    Asthenia 58/284 (20.4%) 37/287 (12.9%)
    Fatigue 69/284 (24.3%) 49/287 (17.1%)
    Mucosal inflammation 52/284 (18.3%) 3/287 (1%)
    Oedema peripheral 41/284 (14.4%) 13/287 (4.5%)
    Pyrexia 40/284 (14.1%) 14/287 (4.9%)
    Infections and infestations
    Nasopharyngitis 22/284 (7.7%) 24/287 (8.4%)
    Upper respiratory tract infection 12/284 (4.2%) 18/287 (6.3%)
    Urinary tract infection 28/284 (9.9%) 12/287 (4.2%)
    Investigations
    Alanine aminotransferase increased 23/284 (8.1%) 16/287 (5.6%)
    Aspartate aminotransferase increased 27/284 (9.5%) 15/287 (5.2%)
    Blood creatinine increased 29/284 (10.2%) 4/287 (1.4%)
    Gamma-glutamyltransferase increased 27/284 (9.5%) 20/287 (7%)
    Lipase increased 17/284 (6%) 11/287 (3.8%)
    Weight decreased 75/284 (26.4%) 6/287 (2.1%)
    Metabolism and nutrition disorders
    Decreased appetite 99/284 (34.9%) 30/287 (10.5%)
    Hyperglycaemia 177/284 (62.3%) 28/287 (9.8%)
    Hypokalaemia 23/284 (8.1%) 5/287 (1.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 32/284 (11.3%) 47/287 (16.4%)
    Back pain 39/284 (13.7%) 37/287 (12.9%)
    Bone pain 10/284 (3.5%) 16/287 (5.6%)
    Muscle spasms 19/284 (6.7%) 11/287 (3.8%)
    Musculoskeletal pain 14/284 (4.9%) 19/287 (6.6%)
    Myalgia 19/284 (6.7%) 8/287 (2.8%)
    Pain in extremity 22/284 (7.7%) 21/287 (7.3%)
    Nervous system disorders
    Dizziness 22/284 (7.7%) 20/287 (7%)
    Dysgeusia 47/284 (16.5%) 10/287 (3.5%)
    Headache 49/284 (17.3%) 38/287 (13.2%)
    Psychiatric disorders
    Insomnia 21/284 (7.4%) 12/287 (4.2%)
    Respiratory, thoracic and mediastinal disorders
    Cough 28/284 (9.9%) 27/287 (9.4%)
    Dyspnoea 23/284 (8.1%) 28/287 (9.8%)
    Skin and subcutaneous tissue disorders
    Alopecia 56/284 (19.7%) 7/287 (2.4%)
    Dry skin 42/284 (14.8%) 10/287 (3.5%)
    Erythema 15/284 (5.3%) 2/287 (0.7%)
    Pruritus 51/284 (18%) 16/287 (5.6%)
    Rash 99/284 (34.9%) 17/287 (5.9%)
    Rash maculo-papular 38/284 (13.4%) 5/287 (1.7%)
    Vascular disorders
    Hot flush 9/284 (3.2%) 19/287 (6.6%)
    Hypertension 23/284 (8.1%) 14/287 (4.9%)
    Lymphoedema 15/284 (5.3%) 6/287 (2.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02437318
    Other Study ID Numbers:
    • CBYL719C2301
    • 2015-000340-42
    First Posted:
    May 7, 2015
    Last Update Posted:
    Aug 10, 2022
    Last Verified:
    Aug 1, 2022