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: 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

ClinicalTrials.gov Identifier: NCT03056755

Novartis Reference Number: CBYL719X2402

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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 
Breast Cancer
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
390 participants
Start date 
Aug 14, 2017
Completion date 
May 31, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
alpelisib
300 mg; oral; once daily
Drug
fulvestrant
500 mg; intramuscular injection on Days 1, 15 on Cycle 1 and Day 1 at each cycle thereafter
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)

Eligibility 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

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

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 monotherapy or in combination except CDK 4/6i + AI) 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/interstitial lung disease which is active and requiring treatment
Patient has a history of severe cutaneous reactions like Stevens-Johnson-Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necroloysis (TEN) or Drug Reaction with Eosinphilia and Systemic Symptoms (DRESS).
Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must be discontinued prior to day one of study treatment.
Subjects with unresolved osteonecrosis of the jaw.

Study Locations

United States
Banner MD Anderson Cancer Center
Recruiting
Gilbert, 85234
Arizona
United States
Mayo Clinic (Arizona)
Recruiting
Phoenix, 85054
Arizona
United States
Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C
Recruiting
Anaheim, 92807
California
United States
Beverly Hills Cancer Center
Recruiting
Beverly Hills, 90211
California
United States
USC Norris Cancer Center
Recruiting
Los Angeles, 90033
California
United States
University of Calif Irvine Medical Center
Recruiting
Orange, 92868
California
United States
Kaiser Permanente Southern California
Recruiting
San Diego, 92120
California
United States
University of California, San Francisco
Recruiting
San Francisco, 94115
California
United States
Cancer Research Collaboration, Inc
Recruiting
Santa Ana, 92705
California
United States
Yale University Yale Cancer Center
Recruiting
New Haven, 06511
Connecticut
United States
Miami Cancer Center at Mercy Hospital
Recruiting
Miami, 33133
Florida
United States
Advent Health Cancer Institute
Recruiting
Orlando, 32804
Florida
United States
University of Iowa Hospitals and Clinics
Recruiting
Iowa City, 52242
Iowa
United States
University of Kansas Cancer Center
Recruiting
Kansas City, 66205
Kansas
United States
University of Louisville Hospital/James Brown Cancer Ctr. SC
Recruiting
Louisville, 40202
Kentucky
United States
Mercy Medical Center
Recruiting
Baltimore, 21202
Maryland
United States
Greater Baltimore Medical Center Cancer Center
Recruiting
Baltimore, 21204-6831
Maryland
United States
Holy Cross Hospital Pharmacy
Recruiting
Silver Spring, 20910
Maryland
United States
Massachusetts General Hospital Neuroendocrine Unit
Recruiting
Boston, 02114
Massachusetts
United States
Lahey Clinic
Recruiting
Burlington, 01805
Massachusetts
United States
Josephine Ford Cancer Institute
Recruiting
Detroit, 48202
Michigan
United States
Washington University School of Medicine
Recruiting
Saint Louis, 63110
Missouri
United States
St Vincent Frontier Cancer Center
Recruiting
Billings, 59102
Montana
United States
New Mexico Cancer Care Alliance
Recruiting
Albuquerque, 87106
New Mexico
United States
Memorial Sloane Kettering Cancer Center
Recruiting
New York, 10065
New York
United States
University Hospitals of Cleveland Seidman Cancer Center
Recruiting
Cleveland, 44106
Ohio
United States
Texas Oncology Charles A. Sammons Cancer Ctr
Recruiting
Dallas, 75246
Texas
United States
Texas Oncology P A SC-3
Recruiting
Dallas, 75251
Texas
United States
Texas Oncology Houston Memorial City
Recruiting
Houston, 77024
Texas
United States
University of Texas MD Anderson Cancer Center
Recruiting
Houston, 77030
Texas
United States
Texas Oncology P A Plano East
Recruiting
Plano, 75075
Texas
United States
Cancer Care Centers of South Texas HOAST CCC of So. TX- San Antonio(2)
Recruiting
San Antonio, 78229
Texas
United States
UT Health San Antonio
Recruiting
San Antonio, 78229
Texas
United States
Virginia Oncology Associates SC
Recruiting
Norfolk, 23502
Virginia
United States
Northwest Medical Specialists
Recruiting
Tacoma, 98405
Washington
United States
Wenatchee Valley Medical Center
Recruiting
Wenatchee, 98801
Washington
United States
Argentina
Novartis Investigative Site
Recruiting
Caba, C1118AAT
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Caba, C1125ABD
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Caba, C1426ANZ
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Rosario, S2000DSV
Santa Fe
Argentina
Novartis Investigative Site
Recruiting
Rosario, S200KZE
Sante Fe
Argentina
Novartis Investigative Site
Recruiting
Cordoba, X5004BAL
-
Argentina
Novartis Investigative Site
Recruiting
La Rioja, 5300
-
Argentina
Novartis Investigative Site
Recruiting
San Juan, J5402DIL
-
Argentina
Belgium
Novartis Investigative Site
Recruiting
Leuven, 3000
-
Belgium
Novartis Investigative Site
Recruiting
Liege, 4000
-
Belgium
Canada
Novartis Investigative Site
Recruiting
Vancouver, V5Z 4E6
British Columbia
Canada
Novartis Investigative Site
Recruiting
Halifax, B3H 2Y9
Nova Scotia
Canada
Novartis Investigative Site
Recruiting
Kitchener, N2G 1G3
Ontario
Canada
Novartis Investigative Site
Recruiting
Toronto, M5B 1N9
Ontario
Canada
Chile
Novartis Investigative Site
Recruiting
Temuco, 4810469
Araucania
Chile
Novartis Investigative Site
Recruiting
Santiago, 7500921
-
Chile
Novartis Investigative Site
Recruiting
Santiago, 8420383
-
Chile
Denmark
Novartis Investigative Site
Recruiting
Copenhagen, DK 2100
-
Denmark
Novartis Investigative Site
Recruiting
Odense C, DK 5000
-
Denmark
Novartis Investigative Site
Recruiting
Vejle, 7100
-
Denmark
France
Novartis Investigative Site
Recruiting
Nice Cedex 2, 06189
Alpes Maritimes
France
Novartis Investigative Site
Recruiting
Saint-Cloud, 92210
Hauts De Seine
France
Novartis Investigative Site
Recruiting
Bordeaux, 33076
-
France
Novartis Investigative Site
Recruiting
Caen Cedex, 14021
-
France
Novartis Investigative Site
Recruiting
Lille Cedex, 59020
-
France
Novartis Investigative Site
Recruiting
Lyon, F-69373
-
France
Novartis Investigative Site
Recruiting
Montpellier Cedex 5, 34298
-
France
Novartis Investigative Site
Recruiting
Saint Herblain cedex, 44805
-
France
Novartis Investigative Site
Recruiting
Strasbourg Cedex, F 67098
-
France
Novartis Investigative Site
Recruiting
Toulouse Cedex 9, 31059
-
France
Germany
Novartis Investigative Site
Recruiting
Augsburg, 86150
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 14169
-
Germany
Novartis Investigative Site
Recruiting
Dresden, 01307
-
Germany
Novartis Investigative Site
Recruiting
Erlangen, 91054
-
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Novartis Investigative Site
Recruiting
Heidelberg, 69120
-
Germany
Novartis Investigative Site
Recruiting
Kiel, 24105
-
Germany
Novartis Investigative Site
Withdrawn
Ravensburg, 88214
-
Germany
Novartis Investigative Site
Recruiting
Troisdorf, 53840
-
Germany
Novartis Investigative Site
Recruiting
Tübingen, 72076
-
Germany
Novartis Investigative Site
Recruiting
Ulm, 89081
-
Germany
India
Novartis Investigative Site
Recruiting
Kolkata, 700160
West Bengal
India
Novartis Investigative Site
Recruiting
Delhi, 110 085
-
India
Israel
Novartis Investigative Site
Recruiting
Kfar Saba, 44281
-
Israel
Novartis Investigative Site
Recruiting
Petach Tikva, 49100
-
Israel
Novartis Investigative Site
Recruiting
Ramat Gan, 52621
-
Israel
Novartis Investigative Site
Recruiting
Rehovot, 7610001
-
Israel
Novartis Investigative Site
Recruiting
Tel Aviv, 6423906
-
Israel
Italy
Novartis Investigative Site
Recruiting
Ancona, 60126
AN
Italy
Novartis Investigative Site
Recruiting
Bergamo, 24127
BG
Italy
Novartis Investigative Site
Recruiting
Genova, 16132
GE
Italy
Novartis Investigative Site
Recruiting
Milano, 20133
MI
Italy
Novartis Investigative Site
Recruiting
Milano, 20141
MI
Italy
Novartis Investigative Site
Recruiting
Roma, 00168
RM
Italy
Novartis Investigative Site
Recruiting
Bologna, 40138
-
Italy
Novartis Investigative Site
Recruiting
Napoli, 80131
-
Italy
Japan
Novartis Investigative Site
Active, not recruiting
Osaka-city, 540-0006
Osaka
Japan
Novartis Investigative Site
Withdrawn
Suita city, 565 0871
Osaka
Japan
Novartis Investigative Site
Withdrawn
Bunkyo ku, 113-8677
Tokyo
Japan
Novartis Investigative Site
Withdrawn
Koto ku, 135 8550
Tokyo
Japan
Novartis Investigative Site
Withdrawn
Shinjuku-ku, 160-0023
Tokyo
Japan
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 06351
-
Korea, Republic of
Mexico
Novartis Investigative Site
Recruiting
Mexico D F, 06760
Distrito Federal
Mexico
Novartis Investigative Site
Recruiting
Jalisco, 45640
-
Mexico
Netherlands
Novartis Investigative Site
Recruiting
Maastricht, 5800
AZ
Netherlands
Singapore
Novartis Investigative Site
Recruiting
Singapore, 169610
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, 217562
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, 258500
-
Singapore
Spain
Novartis Investigative Site
Recruiting
Malaga, 29010
Andalucia
Spain
Novartis Investigative Site
Recruiting
Sevilla, 41013
Andalucia
Spain
Novartis Investigative Site
Recruiting
Salamanca, 37007
Castilla Y Leon
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08036
Catalunya
Spain
Novartis Investigative Site
Recruiting
Hospitalet de LLobregat, 08907
Catalunya
Spain
Novartis Investigative Site
Recruiting
Castellon, 12002
Comunidad Valenciana
Spain
Novartis Investigative Site
Recruiting
San Sebastian, 20080
Pais Vasco
Spain
Novartis Investigative Site
Recruiting
Madrid, 28041
-
Spain
Taiwan
Novartis Investigative Site
Recruiting
Tainan, 70403
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10002
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei,
-
Taiwan
United Kingdom
Novartis Investigative Site
Recruiting
Sutton, SM2 5PT
Surrey
United Kingdom
Novartis Investigative Site
Recruiting
Edinburgh, EH4 2XU
-
United Kingdom
Novartis Investigative Site
Recruiting
Leicester, LE1 5WW
-
United Kingdom
Novartis Investigative Site
Recruiting
London, SW3 6JJ
-
United Kingdom
Novartis Investigative Site
Recruiting
Nottingham, NG5 1PB
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

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