Clinical Trial - NCT03056755

Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutation With Advanced Breast Cancer Who Have Progressed on or After Prior Treatments


Sponsor: Novartis Pharmaceuticals


Information provided by (Responsible party): Sponsor Identifier: NCT03056755

Protocol Info

Short Description: Phase II of Alpelisib + Fulvestrant or Letrozole in PIK3CA Mutant, HR+, HER2- ABC after CDK 4/6 Therapy
Long Description: A Phase II, Multicenter, Open-label, Two-cohort, Non-comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After CDK 4/6 Inhibitor Treatment
MGH Status: Open
Sponsor: Novartis
Disease Program: Breast

Next Steps

If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.


Study assessing the efficacy and safety of alpelisib plus fulvestrant or letrozole, based on prior endocrine therapy, in patients with PIK3CA mutation with advanced breast cancer who have progressed on or after prior treatments
Condition Title Intervention Phase
Breast Cancer alpelisib fulvestrant letrozole Goserelin Leuprolide Phase 2
Study Type Interventional
Official Title BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments

Primary Outcome Measures

The percentage of patients who are alive without disease progression [Time Frame: Date of first dose to approximately 6 months] [Designated as safety issue: ]

Secondary Outcome Measures

Progression free survival (PFS) for each cohort [Time Frame: date of first dose to up to approximately 25 months] [Designated as safety issue: ]

Progression free survival (PFS) on next line treatment PFS2) for each cohort [Time Frame: Date of first dose to date of first documented progression up to approximately 25 months] [Designated as safety issue: ]

Percentage of participants Overall response rate (ORR) for each cohort [Time Frame: Date of first dose and up to approximately 25 months] [Designated as safety issue: ]

Percentage of participants with clinical benefit rate (CBR) for each cohort [Time Frame: Date of first dose and up to approximately 25 months] [Designated as safety issue: ]

Duration of response (DOR) [Time Frame: Date of first documented response to first documented progression or death up to approximately 25 months] [Designated as safety issue: ]

Percentable of overall suvivial (OS) for each cohort [Time Frame: Date of first dose and up to approximately 25 months] [Designated as safety issue: ]

Estimated Enrollment: 336
Study Start Date: August 2017
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: April 2020
Arms Assigned Interventions

Experimental:Prior CDK 4/6 + aromatase

Patients who received any CDK 4/6 inhibitor plus aromatase inhibitor as treatment (immediately prior) will receive alpelisib 500 mg oral.+ fulvestrant 500 mg intramuscular (i.m)
500 mg; intramuscular injection on Days 1, 15 on Cycle 1 and Day 1 at each cycle thereafter

Experimental:Prior CDK 4/6 + fulvestrant

Patients who received any CDK 4/6 inhibitor plus fulvestrant as treatment (immediately prior) will receive alpelisib 300 mg oral + letrozole 2.5 mg oral
Every 28 days (only for men in cohort B and premenopausal women). Administered as injectable intramuscular depot (7.5 mg)

Experimental:Prior systemic chemo or ET

Patients who received systemic chemotherapy or endrocrine therapy (ET) as immediate prior treatment will receive alpelisib 300 mg oral + fulvestrant 500 mg i.m.


Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Patient is male or female 18 years or older
  • Males or females with advanced (locoregionally recurrent or metatstatic) breast cancer not amenable to curative therapy
  • In case of women, both premenopausal and postmenopausal patients are allowed to be included in study; menopausal status is relevant for the requirement of LHRH agonist (examples for use in this study include but not limited to goserelin, leuprolide or locally available treatment) to be used concomitantly with alpelisib and letrozole/fulvestrant

1. Patient is postmenopausal woman defined as either:

  • Prior bilateral oophorectomy or
  • Age ≥60 or
  • Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range.

If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.

Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are needed to ensure menopausal status

2. Patient is premenopausal defined as either:

  • Patient had last menstrual period within the last 12 months or
  • If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, or
  • In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range
  • Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC
  • Patient has confirmed HER2-negative advanced breast cancer (aBC)
  • Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient has a pathology report confirming PIK3CA mutant status by certified laboratory (using validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send tumor tissue to Novartis designated central lab for confirmation of mutational status
  • Patient must have:
  • Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior to study entry,
  • AI treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET as last treatment regimen in cohort C
  • Maintenance therapies, where applicable, must be regarded as part of the main treatment.
  • No more than two (2) prior anti-cancer therapies for aBC
  • Received no more than one prior regimen of chemotherapy in the metastatic setting
  • Patient has either measurable disease per RECIST v1.1 or at least one predominantly lytic bone lesion must be present
  • ECOG performance status ≤ 2
  • Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met)
  • Patient has adequate bone marrow, coagulation, liver and renal function

Exclusion Criteria:

  • patient has known hypersensitivity to alpelisib, fulvestrant or letrozole
  • Patient has received prior treatment with any PI3K inhibitors
  • Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type II
  • Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer
  • Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy
  • History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis
  • Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
  • At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
  • Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (MRI or CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment
  • Patient with severe liver impairment (Child Pugh score B/C)
  • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs
  • Patient has documented pneumonitis which is active and requiring treatment
  • Patient has a history of Stevens-Johnson-Syndrome (SJS) or Toxic Epidermal Necroloysis (TEN)
  • Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must be discontinued prior to day one of study treatment.

Contacts and Locations

Please refer to this study by its identifier: NCT03056755


  • United States, Arizona
    • Banner MD Anderson Cancer Center Gilbert, Arizona, United States, 85234
    • Mayo Clinic (Arizona) Phoenix, Arizona, United States, 85054
  • United States, California
    • Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C Anaheim, California, United States, 92807
    • Beverly Hills Cancer Center Beverly Hills, California, United States, 90211
    • USC Norris Cancer Center Los Angeles, California, United States, 90033
    • University of Calif Irvine Medical Center Orange, California, United States, 92868
    • Kaiser Permanente Southern California San Diego, California, United States, 92120
    • University of California, San Francisco San Francisco, California, United States, 94115
    • Cancer Research Collaboration, Inc Santa Ana, California, United States, 92705
  • United States, Connecticut
    • Yale University Yale Cancer Center New Haven, Connecticut, United States, 06511
  • United States, Florida
    • Florida Hospital Cancer Center Orlando, Florida, United States, 32804
  • United States, Iowa
    • University of Iowa Hospitals and Clinics Iowa City, Iowa, United States, 52242
  • United States, Kansas
    • University of Kansas Cancer Center Kansas City, Kansas, United States, 66205
  • United States, Kentucky
    • University of Louisville Hospital/James Brown Cancer Ctr. SC Louisville, Kentucky, United States, 40202
  • United States, Maryland
    • Mercy Medical Center Baltimore, Maryland, United States, 21202
    • Greater Baltimore Medical Center Cancer Center Baltimore, Maryland, United States, 21204-6831
  • United States, Massachusetts
    • Massachusetts General Hospital Neuroendocrine Unit Boston, Massachusetts, United States, 02114
    • Lahey Clinic Burlington, Massachusetts, United States, 01805
  • United States, Michigan
    • Josephine Ford Cancer Institute Detroit, Michigan, United States, 48202
  • United States, Montana
    • St Vincent Frontier Cancer Center Billings, Montana, United States, 59102
  • United States, New Mexico
    • New Mexico Cancer Care Alliance Albuquerque, New Mexico, United States, 87106
  • United States, New York
    • Memorial Sloane Kettering Cancer Center New York, New York, United States, 10065
  • United States, Ohio
    • University Hospitals of Cleveland Seidman Cancer Center Cleveland, Ohio, United States, 44106
  • United States, Texas
    • UT Health San Antonio San Antonio, Texas, United States, 78229
  • United States, Washington
    • Northwest Medical Specialists Tacoma, Washington, United States, 98405
    • Wenatchee Valley Medical Center Wenatchee, Washington, United States, 98801
  • Argentina, Buenos Aires
    • Novartis Investigative Site Caba, Buenos Aires, Argentina, C1118AAT
    • Novartis Investigative Site Caba, Buenos Aires, Argentina, C1125ABD
    • Novartis Investigative Site Caba, Buenos Aires, Argentina, C1426ANZ
  • Argentina, Sante Fe
    • Novartis Investigative Site Rosario, Sante Fe, Argentina, S200KZE
  • Argentina,
    • Novartis Investigative Site La Rioja, , Argentina, 5300
  • Belgium,
    • Novartis Investigative Site Leuven, , Belgium, 3000
    • Novartis Investigative Site Liege, , Belgium, 4000
  • Canada, British Columbia
    • Novartis Investigative Site Vancouver, British Columbia, Canada, V5Z 4E6
  • Canada, Nova Scotia
    • Novartis Investigative Site Halifax, Nova Scotia, Canada, B3H 2Y9
  • Canada, Ontario
    • Novartis Investigative Site Kitchener, Ontario, Canada, N2G 1G3
    • Novartis Investigative Site Toronto, Ontario, Canada, M5B 1N9
  • Chile, Araucania
    • Novartis Investigative Site Temuco, Araucania, Chile, 4810469
  • Chile,
    • Novartis Investigative Site Santiago, , Chile, 7500921
  • France, Alpes Maritimes
    • Novartis Investigative Site Nice Cedex 2, Alpes Maritimes, France, 06189
  • France, Hauts De Seine
    • Novartis Investigative Site Saint-Cloud, Hauts De Seine, France, 92210
  • France,
    • Novartis Investigative Site Bordeaux, , France, 33076
    • Novartis Investigative Site Caen Cedex, , France, 14021
    • Novartis Investigative Site Lille Cedex, , France, 59020
    • Novartis Investigative Site Lyon, , France, F-69373
    • Novartis Investigative Site Montpellier Cedex 5, , France, 34298
    • Novartis Investigative Site Saint Herblain cedex, , France, 44805
    • Novartis Investigative Site Strasbourg Cedex, , France, 67091
    • Novartis Investigative Site Toulouse Cedex 9, , France, 31059
  • Germany,
    • Novartis Investigative Site Augsburg, , Germany, 86150
    • Novartis Investigative Site Berlin, , Germany, 14169
    • Novartis Investigative Site Dresden, , Germany, 01307
    • Novartis Investigative Site Erlangen, , Germany, 91054
    • Novartis Investigative Site Essen, , Germany, 45147
    • Novartis Investigative Site Kiel, , Germany, 24105
    • Novartis Investigative Site Ravensburg, , Germany, 88214
    • Novartis Investigative Site Troisdorf, , Germany, 53840
    • Novartis Investigative Site Tübingen, , Germany, 72076
    • Novartis Investigative Site Ulm, , Germany, 89081
  • India, West Bengal
    • Novartis Investigative Site Kolkata, West Bengal, India, 700160
  • India,
    • Novartis Investigative Site Delhi, , India, 110 085
  • Israel,
    • Novartis Investigative Site Petach Tikva, , Israel, 49100
    • Novartis Investigative Site Ramat Gan, , Israel, 5265601
    • Novartis Investigative Site Rehovot, , Israel, 7610001
    • Novartis Investigative Site Tel Aviv, , Israel, 6423906
  • Italy, MI
    • Novartis Investigative Site Milano, MI, Italy, 20133
    • Novartis Investigative Site Milano, MI, Italy, 20141
  • Italy,
    • Novartis Investigative Site Bologna, , Italy, 40138
    • Novartis Investigative Site Napoli, , Italy, 80131
  • Japan, Osaka
    • Novartis Investigative Site Osaka-city, Osaka, Japan, 540-0006
    • Novartis Investigative Site Suita city, Osaka, Japan, 565 0871
  • Japan, Tokyo
    • Novartis Investigative Site Bunkyo-ku, Tokyo, Japan, 113-8677
    • Novartis Investigative Site Koto ku, Tokyo, Japan, 135 8550
    • Novartis Investigative Site Shinjuku-ku, Tokyo, Japan, 160-0023
  • Korea, Republic of,
    • Novartis Investigative Site Seoul, , Korea, Republic of, 03080
    • Novartis Investigative Site Seoul, , Korea, Republic of, 06351
  • Mexico, Distrito Federal
    • Novartis Investigative Site Mexico D F, Distrito Federal, Mexico, 06760
  • Mexico,
    • Novartis Investigative Site Jalisco, , Mexico, 45640
  • Netherlands, AZ
    • Novartis Investigative Site Maastricht, AZ, Netherlands, 5800
  • Singapore,
    • Novartis Investigative Site Singapore, , Singapore, 169610
  • Spain, Andalucia
    • Novartis Investigative Site Sevilla, Andalucia, Spain, 41013
  • Spain, Catalunya
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08035
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08036
    • Novartis Investigative Site Hospitalet de LLobregat, Catalunya, Spain, 08907
  • Spain, Comunidad Valenciana
    • Novartis Investigative Site Castellon, Comunidad Valenciana, Spain, 12002
  • Spain,
    • Novartis Investigative Site Madrid, , Spain, 28041
  • United Kingdom, Surrey
    • Novartis Investigative Site Sutton, Surrey, United Kingdom, SM2 5PT
  • United Kingdom,
    • Novartis Investigative Site Edinburgh, , United Kingdom, EH4 2XU
    • Novartis Investigative Site Leicester, , United Kingdom, LE1 5WW
    • Novartis Investigative Site London, , United Kingdom, SW3 6JJ
    • Novartis Investigative Site Nottingham, , United Kingdom, NG5 1PB

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party: Sponsor Identifier: NCT03056755
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Novartis:

advanced breast cancer


CDK 4/6 inhibitor





post menopausal


aromatase inhibitor

endocrine treatment



Additional relevant MeSH terms:

Breast Neoplasms





Aromatase Inhibitors

Next Steps

If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation. processed this data on May 30, 2019