Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss Without PIK3CA Mutation

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Nab-paclitaxel in Patients With Advanced Triple Negative Breast Cancer With Either Phosphoinositide-3-kinase Catalytic Subunit Alpha (PIK3CA) Mutation or Phosphatase and Tensin Homolog Protein (PTEN) Loss Without PIK3CA Mutation

ClinicalTrials.gov Identifier: NCT04251533

Novartis Reference Number: CBYL719H12301

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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

The purpose of this study is to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced triple negative breast cancer (aTNBC) who carry either a PIK3CA mutation (Study Part A) or have PTEN loss without PIK3CA mutation (Study Parts B1 and B2)

Condition 
Triple Negative Breast Neoplasms
Phase 
Phase 3
Overall status 
Recruiting
Enrollment count 
566 participants
Start date 
Jun 08, 2020
Completion date 
Nov 24, 2025
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
alpelisib
300 mg orally once per day (QD)
Drug
placebo
300 mg orally once per day (QD)
Drug
nab-paclitaxel
100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle

Eligibility Criteria

Inclusion Criteria:

Subject has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy, or metastatic (stage IV)) TNBC
Subject has either a measurable disease per RECIST 1.1 criteria or, if no measurable disease is present, then at least one predominantly lytic bone lesion or mixed lytic-blastic bone lesion with identifiable soft tissue component (that can be evaluated by CT/MRI) must be present Part B1: patients must have measurable disease
Subject has adequate tumor tissue to identify the PIK3CA mutation status (either carrying a mutation or without a mutation) and the PTEN loss status; both of which will determine whether the subject can be allocated to Part A - PIK3CA mutation regardless of PTEN status; or to Part B - PTEN loss without a PIK3CA mutation
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Subject has received no more than one line of therapy for metastatic disease.
Subject has adequate bone marrow and organ function

Exclusion Criteria:

Subject has received prior treatment with any PI3K, mTOR or AKT inhibitor
Subject has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their excipients
Subject has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1; with the exception of alopecia
Subject has central nervous system (CNS) involvement
Subject with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on Fasting Plasma Glucose and HbA1c
Subject has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) based on investigator discretion
Subject has a history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
Subject has currently documented pneumonitis/interstitial lung disease
Subject has a history of severe cutaneous reactions, such as Steven-Johnson Syndrome (SJS), erythema multiforme (EM),Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS)
Subject with unresolved osteonecrosis of the jaw

Other protocol-defined inclusion/exclusion criteria apply.

Study Locations

United States
Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
Recruiting
Las Vegas, 89109
Nevada
United States
Cleveland Clinic Foundation Taussig Cancer Center
Recruiting
Cleveland, 44195
Ohio
United States
Texas Oncology, P.A. Austin
Recruiting
Bedford, 76022
Texas
United States
Texas Oncology PA Dallas Presbyterian Hospital SC
Recruiting
Dallas, 75231
Texas
United States
Texas Oncology Texas Oncology - Denton
Recruiting
Dallas, 75246
Texas
United States
El Paso, Texas Oncology
Recruiting
El Paso, 79902
Texas
United States
Australia
Novartis Investigative Site
Recruiting
Murdoch, 6150
Western Australia
Australia
Novartis Investigative Site
Recruiting
Nedlands, 6009
Western Australia
Australia
Brazil
Novartis Investigative Site
Recruiting
Sao Paulo, 03102-002
SP
Brazil
France
Novartis Investigative Site
Recruiting
Angers Cedex 02, 49055
-
France
Novartis Investigative Site
Recruiting
Besancon Cedex, 25030
-
France
Novartis Investigative Site
Recruiting
Clermont-Ferrand, 63011
-
France
Novartis Investigative Site
Recruiting
Creteil, 94010
-
France
Novartis Investigative Site
Recruiting
Metz, 57085
-
France
Novartis Investigative Site
Recruiting
Paris Cedex 10, 75475
-
France
Novartis Investigative Site
Recruiting
Poitiers, 86000
-
France
Novartis Investigative Site
Recruiting
Reims, 51100
-
France
Novartis Investigative Site
Recruiting
Saint-Herblain Cédex, 44805
-
France
Germany
Novartis Investigative Site
Recruiting
Ravensburg, 88212
Baden-Wuerttemberg
Germany
Novartis Investigative Site
Recruiting
Muenchen, 80637
Bavaria
Germany
Novartis Investigative Site
Recruiting
Velbert, 42551
North Rhine-westphalia
Germany
Novartis Investigative Site
Recruiting
Erlangen, 91054
-
Germany
Novartis Investigative Site
Recruiting
Leipzig, 04103
-
Germany
Novartis Investigative Site
Recruiting
Tübingen, 72076
-
Germany
Hungary
Novartis Investigative Site
Recruiting
Debrecen, 4032
-
Hungary
Novartis Investigative Site
Recruiting
Kecskemet, 6000
-
Hungary
Novartis Investigative Site
Recruiting
Tatabanya, H 2800
-
Hungary
Israel
Novartis Investigative Site
Recruiting
Be'er Sheva, 84101
-
Israel
Novartis Investigative Site
Recruiting
Tel Aviv, 6423906
-
Israel
Italy
Novartis Investigative Site
Recruiting
Messina, 98158
ME
Italy
Novartis Investigative Site
Recruiting
Roma, 00128
RM
Italy
Malaysia
Novartis Investigative Site
Recruiting
Petaling Jaya, 46050
Selangor
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 59100
-
Malaysia
Norway
Novartis Investigative Site
Recruiting
Oslo, NO 0450
-
Norway
Novartis Investigative Site
Recruiting
Stavanger, 4019
-
Norway
Russian Federation
Novartis Investigative Site
Recruiting
Arkhangelsk, 163045
-
Russian Federation
Novartis Investigative Site
Recruiting
Chelyabinsk, 454048
-
Russian Federation
Novartis Investigative Site
Recruiting
Moscow, 117997
-
Russian Federation
Novartis Investigative Site
Recruiting
Moscow, 123056
-
Russian Federation
Novartis Investigative Site
Recruiting
Moscow, 143423
-
Russian Federation
Novartis Investigative Site
Recruiting
Pushkin Saint Petersburg, 196603
-
Russian Federation
Slovakia
Novartis Investigative Site
Recruiting
Bratislava, 812 50
-
Slovakia
Novartis Investigative Site
Recruiting
Kosice, 041 91
-
Slovakia
Spain
Novartis Investigative Site
Recruiting
Madrid, 28041
-
Spain
Switzerland
Novartis Investigative Site
Recruiting
Aarau, 5000
-
Switzerland
Novartis Investigative Site
Recruiting
Zurich, 8008
-
Switzerland
Taiwan
Novartis Investigative Site
Recruiting
Taichung, 40447
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10002
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10449
-
Taiwan
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: 

Have a question?

Call 1-999-669-6682 or email [email protected]