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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 (BYLieve)

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ClinicalTrials.gov Identifier: NCT03056755
Recruitment Status : Recruiting
First Posted : February 17, 2017
Last Update Posted : August 5, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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 or disease Intervention/treatment Phase
Breast Cancer Drug: alpelisib Drug: fulvestrant Drug: letrozole Drug: Goserelin Drug: Leuprolide Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 340 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a phase II, multicenter, open-label, three-cohort, non-comparative study of alpelisib plus endocrine therapy (either fulvestrant or letrozole) in patients with HR+, HER2-negative aBC harboring PIK3CA mutation(s) in the tumor whose disease has progressed on or after prior treatments
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 14, 2017
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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)
Drug: alpelisib
300 mg; oral; once daily
Other Name: BYL719

Drug: fulvestrant
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
Drug: alpelisib
300 mg; oral; once daily
Other Name: BYL719

Drug: letrozole
2.5 mg; oral; once daily

Drug: Goserelin
Every 28 days (only for men in cohort B and premenopausal women). Administered as injectable subcutaneous implant (3.6 mg)

Drug: Leuprolide
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.
Drug: alpelisib
300 mg; oral; once daily
Other Name: BYL719

Drug: fulvestrant
500 mg; intramuscular injection on Days 1, 15 on Cycle 1 and Day 1 at each cycle thereafter




Primary Outcome Measures :
  1. The percentage of patients who are alive without disease progression [ Time Frame: Date of first dose to approximately 6 months ]
    Assess the percentage of patients without disease progression based on local investigator assessment per RECIST in cohort A, cohort B and cohort C


Secondary Outcome Measures :
  1. Progression free survival (PFS) for each cohort [ Time Frame: date of first dose to up to approximately 25 months ]
    PFS is defined as the time from the date of first dose of study medication to the date of the first documented progression or death due to any cause occurring in the study. PFS will be assessed based on local investigator's assessment according to RECIST v1.1

  2. 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 ]
    Progression free survival (PFS) on next line treatment (PFS2) is defined as time from the date of first dose of study medication to the date of first documented progression on next-line therapy or death from any cause

  3. Percentage of participants Overall response rate (ORR) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
    ORR based on local investigator's assessment according to RECIST v1.1 in each cohort

  4. Percentage of participants with clinical benefit rate (CBR) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
    Clinical Benefit Rate (CBR) based on local investigator's assessment according to RECIST v1.1 in each cohort

  5. Duration of response (DOR) [ Time Frame: Date of first documented response to first documented progression or death up to approximately 25 months ]
    Duration of Response is the time from the date of first documented response (confirmed CR or PR) to the date of first documented progression or death due to underlying cancer

  6. Percentable of overall suvivial (OS) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
    Overall Survival is defined as the time of start of treatment to date of death or lost to follow-up.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03056755


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

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Locations
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United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Cindy Sidwa    *see departments*    cindy.sidwa@bannerhealth.com   
Principal Investigator: Shakeela Bahadur         
Mayo Clinic (Arizona) Recruiting
Phoenix, Arizona, United States, 85054
Contact: Ashley Herbst    480-342-6429    herbst.ashley@mayo.edu   
Principal Investigator: Donald W Northfelt         
United States, California
Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C Recruiting
Anaheim, California, United States, 92807
Contact: Jennifer Nakano    808-432-8587    salljen@aol.com   
Principal Investigator: Jennifer Carney         
Beverly Hills Cancer Center Recruiting
Beverly Hills, California, United States, 90211
Contact: Francisco Capilla    310-432-8900    fcapilla@bhcancercenter.com   
Principal Investigator: Linea Chap         
USC Norris Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: America Lopez-Casillas    323-865-3955    America.Casillas-Lopez@med.usc.edu   
Principal Investigator: Janice Lu         
University of Calif Irvine Medical Center Recruiting
Orange, California, United States, 92868
Contact: Sonny Tong    714-456-5376    sonnykt@uci.edu   
Principal Investigator: Ritesh Parajuli         
Kaiser Permanente Southern California Recruiting
San Diego, California, United States, 92120
Contact: Angela J Rohan    619-528-3955    Angela.X.Rohan@kp.org   
Principal Investigator: Jonathan Polikoff         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94115
Contact: Maha Kadafour    415-885-3789    Maha.Kadafour@ucsf.edu   
Principal Investigator: Hope S Rugo         
Cancer Research Collaboration, Inc Recruiting
Santa Ana, California, United States, 92705
Contact: Deidre Carrillo    562-981-6101    deidre.carrillo@cancercollaboration.org   
Principal Investigator: John Link         
United States, Connecticut
Yale University Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06511
Contact: Thomas Ferencz    203-737-2848    Thomas.ferencz@ynhh.org   
Principal Investigator: Andrea Silber         
United States, Florida
Florida Hospital Cancer Center Recruiting
Orlando, Florida, United States, 32804
Contact: Sara Guyler    407-303-3235    sara.guyler@flhosp.org   
Principal Investigator: Carlos A. Alemany         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Marian Andersen    319-356-1826    Marian-andersen@uiowa.edu   
Principal Investigator: Sneha Phadke         
United States, Kansas
University of Kansas Cancer Center Recruiting
Kansas City, Kansas, United States, 66205
Contact: Deborah Bayer    913-945-5052    dbayer@kumc.edu   
Principal Investigator: Qamar J Khan         
United States, Kentucky
University of Louisville Hospital/James Brown Cancer Ctr. SC Recruiting
Louisville, Kentucky, United States, 40202
Contact: Sandrine Niyiragira    502-562-4356    Sandrine.Niyiragira@louisville.edu   
Principal Investigator: Mounika Mandadi         
United States, Maryland
Mercy Medical Center Recruiting
Baltimore, Maryland, United States, 21202
Contact: Lisa McConnell    410-332-1200    lmcconnell@mdmercy.com   
Principal Investigator: David Andrew Riseberg         
Greater Baltimore Medical Center Cancer Center Recruiting
Baltimore, Maryland, United States, 21204-6831
Contact: Steven Schmitt    410-528-3058    sschmitt@gbmc.org   
Principal Investigator: Madhu Chaudhry         
United States, Massachusetts
Massachusetts General Hospital Neuroendocrine Unit Recruiting
Boston, Massachusetts, United States, 02114
Contact: Rachel Hepp    617-724-0878    rhepp@mgh.harvard.edu   
Principal Investigator: Dejan Juric         
Lahey Clinic Recruiting
Burlington, Massachusetts, United States, 01805
Contact: Julie Roache    781-744-2500    julie.roach@lahey.org   
Principal Investigator: Corrine Zarwan         
United States, Michigan
Josephine Ford Cancer Institute Recruiting
Detroit, Michigan, United States, 48202
Contact: Chelsea Gholston    313-916-2438    Cgholst1@hfhs.org   
Principal Investigator: Haythem Ali         
United States, Montana
St Vincent Frontier Cancer Center Recruiting
Billings, Montana, United States, 59102
Contact: Susan Wells    406-238-6962    susan.wells@sclhs.net   
Principal Investigator: Patrick Cobb         
United States, New Mexico
New Mexico Cancer Care Alliance Recruiting
Albuquerque, New Mexico, United States, 87106
Contact: Kaylee Deutsch    505-925-0366    kdeutsch@nmcca.org   
Principal Investigator: Ursa Brown-Glaberman         
United States, New York
Memorial Sloane Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Afra Yehwalashet    646-888-5341    yehwalaa@mskcc.org   
Principal Investigator: Pamela Drullinsky         
United States, Ohio
University Hospitals of Cleveland Seidman Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Mary Corl    216-844-5176    Mary.Corl@Uhhospitals.org   
Principal Investigator: Paula Silverman         
United States, Texas
UT Health San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Kathleen F Rodriguez    210-450-1366    rodriguezk3@uthscsa.edu   
Principal Investigator: Virginia Kaklamani         
United States, Washington
Northwest Medical Specialists Recruiting
Tacoma, Washington, United States, 98405
Contact: Patti Walsh    253-396-5329    pwalsh@nwmsonline.com   
Principal Investigator: Sibel Blau         
Wenatchee Valley Medical Center Recruiting
Wenatchee, Washington, United States, 98801
Contact: Crystal Adams    509-665-5800    crystal.adams@confluencehealth.org   
Principal Investigator: Lindsay Overton         
Argentina
Novartis Investigative Site Recruiting
Caba, Buenos Aires, Argentina, C1118AAT
Novartis Investigative Site Recruiting
Caba, Buenos Aires, Argentina, C1125ABD
Novartis Investigative Site Recruiting
Caba, Buenos Aires, Argentina, C1426ANZ
Novartis Investigative Site Recruiting
Rosario, Sante Fe, Argentina, S200KZE
Novartis Investigative Site Recruiting
La Rioja, Argentina, 5300
Belgium
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Novartis Investigative Site Recruiting
Liege, Belgium, 4000
Canada, British Columbia
Novartis Investigative Site Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Nova Scotia
Novartis Investigative Site Recruiting
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Novartis Investigative Site Recruiting
Kitchener, Ontario, Canada, N2G 1G3
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5B 1N9
Chile
Novartis Investigative Site Recruiting
Temuco, Araucania, Chile, 4810469
Novartis Investigative Site Recruiting
Santiago, Chile, 7500921
Denmark
Novartis Investigative Site Recruiting
Vejle, Denmark, 7100
France
Novartis Investigative Site Recruiting
Nice Cedex 2, Alpes Maritimes, France, 06189
Novartis Investigative Site Recruiting
Saint-Cloud, Hauts De Seine, France, 92210
Novartis Investigative Site Recruiting
Bordeaux, France, 33076
Novartis Investigative Site Recruiting
Caen Cedex, France, 14021
Novartis Investigative Site Recruiting
Lille Cedex, France, 59020
Novartis Investigative Site Recruiting
Lyon, France, F-69373
Novartis Investigative Site Recruiting
Montpellier Cedex 5, France, 34298
Novartis Investigative Site Recruiting
Saint Herblain cedex, France, 44805
Novartis Investigative Site Recruiting
Strasbourg Cedex, France, 67091
Novartis Investigative Site Recruiting
Toulouse Cedex 9, France, 31059
Germany
Novartis Investigative Site Recruiting
Augsburg, Germany, 86150
Novartis Investigative Site Recruiting
Berlin, Germany, 14169
Novartis Investigative Site Recruiting
Dresden, Germany, 01307
Novartis Investigative Site Recruiting
Erlangen, Germany, 91054
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Recruiting
Heidelberg, Germany, 69120
Novartis Investigative Site Recruiting
Kiel, Germany, 24105
Novartis Investigative Site Recruiting
Ravensburg, Germany, 88214
Novartis Investigative Site Recruiting
Troisdorf, Germany, 53840
Novartis Investigative Site Recruiting
Tübingen, Germany, 72076
Novartis Investigative Site Recruiting
Ulm, Germany, 89081
India
Novartis Investigative Site Recruiting
Kolkata, West Bengal, India, 700160
Novartis Investigative Site Recruiting
Delhi, India, 110 085
Israel
Novartis Investigative Site Recruiting
Petach Tikva, Israel, 49100
Novartis Investigative Site Recruiting
Ramat Gan, Israel, 5265601
Novartis Investigative Site Recruiting
Rehovot, Israel, 7610001
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 6423906
Italy
Novartis Investigative Site Recruiting
Bergamo, BG, Italy, 24127
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20141
Novartis Investigative Site Recruiting
Bologna, Italy, 40138
Novartis Investigative Site Recruiting
Napoli, Italy, 80131
Japan
Novartis Investigative Site Recruiting
Osaka-city, Osaka, Japan, 540-0006
Novartis Investigative Site Recruiting
Suita city, Osaka, Japan, 565 0871
Novartis Investigative Site Recruiting
Bunkyo ku, Tokyo, Japan, 113-8677
Novartis Investigative Site Recruiting
Koto ku, Tokyo, Japan, 135 8550
Novartis Investigative Site Recruiting
Shinjuku-ku, Tokyo, Japan, 160-0023
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 06351
Mexico
Novartis Investigative Site Recruiting
Mexico D F, Distrito Federal, Mexico, 06760
Novartis Investigative Site Completed
Jalisco, Mexico, 45640
Netherlands
Novartis Investigative Site Recruiting
Maastricht, AZ, Netherlands, 5800
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Novartis Investigative Site Recruiting
Singapore, Singapore, 217562
Spain
Novartis Investigative Site Recruiting
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site Recruiting
Castellon, Comunidad Valenciana, Spain, 12002
Novartis Investigative Site Recruiting
Madrid, Spain, 28041
United Kingdom
Novartis Investigative Site Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Novartis Investigative Site Recruiting
Edinburgh, United Kingdom, EH4 2XU
Novartis Investigative Site Recruiting
Leicester, United Kingdom, LE1 5WW
Novartis Investigative Site Recruiting
London, United Kingdom, SW3 6JJ
Novartis Investigative Site Recruiting
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03056755     History of Changes
Other Study ID Numbers: CBYL719X2402
First Posted: February 17, 2017    Key Record Dates
Last Update Posted: August 5, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
advanced breast cancer
PIK3CA
CDK 4/6 inhibitor
fulvestrant
letrozole
HR+
HER-negative
post menopausal
pre-menopausal
aromatase inhibitor
endocrine treatment
AI
ET

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Fulvestrant
Leuprolide
Goserelin
Aromatase Inhibitors
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents