Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation

EPIK-B2: A Two Part, Phase III, Multicenter, Randomized (1:1), Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation

ClinicalTrials.gov Identifier: NCT04208178

Novartis Reference Number: CBYL719G12301

Last Update: Nov 14, 2022

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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 two part multicenter, randomized, double-blind, placebo-controlled, Phase III study is to evaluate the efficacy and safety of alpelisib compared to alpelisib matching-placebo in combination with trastuzumab and pertuzumab as maintenance treatment of patients with HER2-positive advanced breast cancer whose tumor harbors a PIK3CA mutation following induction therapy with a taxane in combination with trastuzumab and pertuzumab. Part 1 is the open-label, safety run-in part of the study, designed to confirm the recommended phase 3 dose (RP3D) dose of alpelisib in combination with trastuzumab and pertuzumab. Following Part 1, Part 2 will be initiated, which is the randomized, Phase III part of the study.

Condition 
Advanced HER2+Breast Cancer
Phase 
Phase 3
Overall status 
Recruiting
Start date 
Jul 16, 2020
Completion date 
Jul 15, 2031
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Alpelisib
Alpelisib orally taken - continuous once daily, in a 21-day cycle.
Drug
Alpelisib matching Placebo
Alpelisib matching placebo orally taken - continuous once daily, in a 21-day cycle
Drug
Trastuzumab
Trastuzumab 6mg/kg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)
Drug
Pertuzumab
Pertuzumab 420 mg given intravenously - Day 1 of Cycle 1, and on Day 1 of every cycle thereafter (Cycle=21 days)

Eligibility Criteria

Inclusion Criteria:

Participant has histologically-confirmed HER2-positive breast cancer that is advanced (loco-regionally not amenable to surgery or is metastatic).
Participant has received pre-study induction therapy with up to and including a maximum of 8 cycles of a taxane (docetaxel, paclitaxel, or nab-paclitaxel), plus trastuzumab and pertuzumab. 4 or 5 cycles of induction therapy are permitted if discontinuation of taxane was due to taxane toxicity. Of note, participants enrolled in Part 1 of this study received 4-6 cycles of pre-study induction therapy.
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Participant has adequate bone marrow and organ function
Applies only to Part 2: Participant has a PIK3CA mutation(s) present in tumor prior to enrollment, locally confirmed per test listed in protocol or as determined by a Novartis designated central laboratory.

Exclusion Criteria:

Participant with inflammatory breast cancer at screening.
Participant with evidence of disease progression during the pre-study induction therapy and prior to first dose of alpelisib (or alpelisib/alpelisib matching-placebo for Part 2)
Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on fasting plasma glucose (FPG) and HbA1c.
Participant has a known history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
Participant has clinically significant, uncontrolled heart disease and/or recent cardiac events
Participant has a history of Steven-Johnson Syndrome (SJS), erythema multiforme (EM) or Toxic Epidermal Necrolysis (TEN).
Participant has currently documented pneumonitis/interstitial lung disease

Other protocol-defined Inclusion/Exclusion may apply.

Study Locations

United States
Highlands Oncology Group Main
Recruiting
Fayetteville, 72703 - Arkansas
Contact: Alyssabeth Parsley (479-872-8130) - [email protected] - J. Thaddeus Beck
United States
Marin Cancer Care
Recruiting
Greenbrae, 94904 - California
Contact: Melissa Chafoya (415-925-5000) - [email protected] - Kristin Anderson
United States
UCLA Medical Center Reg-5
Recruiting
Los Angeles, 90095 - California
Contact: Helene Yang (+1 301 206 8309) - [email protected] - Sara Alsterlind Hurvitz
United States
Queen of the Valley Medical Center
Recruiting
Napa, 94558 - California
Contact: Teresa Lund (707-521-3814) - [email protected] - Gurinder Sidhu
United States
St Joseph Heritage Healthcare
Recruiting
Santa Rosa, 94503 - California
Contact: Teresa Lund (707-542-2783) - [email protected] - Manasa Vulchi
United States
Rocky Mountain Cancer Centers Rocky Mountain Cancer Ctr (50)
Recruiting
Longmont, 80501 - Colorado
Contact: Lorena Alvarez (714-835-1800) - [email protected] - Lori L Jensen
United States
Northwestern University Drug Shipment
Recruiting
Chicago, 60611 - Illinois
Contact: Nina Garcia (312-926-7470) - [email protected] - William J. Gradishar
United States
Clinical Research Alliance Administrative Office
Recruiting
Lake Success, 11042 - New York
Contact: Arelene Perez (+1 516 488 2918 ext 183) - [email protected] - Morton Coleman
United States
Memorial Sloan Kettering Cancer Center Drug Ship - 2
Recruiting
New York, 10065 - New York
Contact: Betty Mar (212-639-8186) - [email protected] - Sarat Chandarlapaty
United States
Univ of Pittsburg Med Ctr Pinnacle
Recruiting
Harrisburg, 17109 - Pennsylvania
Contact: Barbara Heim (717-652-3000) - [email protected] - Kit Lu
United States
Texas Oncology McKinney
Recruiting
Allen, 75013 - Texas
Contact: Christy DeCastro - [email protected] - Monte Jones
United States
Texas Oncology, P.A. Austin
Recruiting
Bedford, 76022 - Texas
Contact: Amy Ressel (512-421-4163) - [email protected] - Debra A Patt
United States
Presbyterian Hospital of Dallas [email protected]
Recruiting
Dallas, 75231 - Texas
Contact: Nancy Jones (214-346-3508) - [email protected] - Kristi J McIntyre
United States
Texas Oncology Flower Mound Texas Oncology, PA
Recruiting
Dallas, 75234 - Texas
Contact: Tiffany Perry (972-537-4100) - [email protected] - Vibha Thomas
United States
Texas Oncology Baylor Charles A Sammons Cancer Ctr
Recruiting
Dallas, 75246 - Texas
Contact: Julie Morehouse - [email protected] - Joyce A O Shaughnessy
United States
Texas Oncology P A TX Onc - Med City Dallas
Recruiting
Dallas, 75251 - Texas
Contact: (972-566-4291) Jay Courtright
United States
Lumi Research
Recruiting
Kingwood, 77339 - Texas
Contact: Kimberly Pair (281-809-0676) - [email protected] - Saleha Sajid
United States
Texas Oncology P A
Recruiting
San Antonio, 78217 - Texas
Contact: Rachel Schearer - [email protected] - Emmalind Aponte
United States
University of Wisconsin Regulatory Contact
Recruiting
Madison, 53792 - Wisconsin
Contact: Jamie Elsen (608-262-6873) - [email protected] - Mark Burkard
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