Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01923168
Recruitment Status : Completed
First Posted : August 15, 2013
Last Update Posted : April 20, 2018
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of the study is to determine whether treatment with a PI3K inhibitor plus letrozole leads to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: BYL719 Drug: BKM120 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 340 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-blind Placebo Controlled, Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women With Hormone Receptor-positive HER2-negative Breast Cancer
Actual Study Start Date : March 11, 2014
Actual Primary Completion Date : July 7, 2017
Actual Study Completion Date : July 8, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Letrozole

Arm Intervention/treatment
Experimental: BYL719 + Letrozole
BYL719 + Letrozole in 120 patients
Drug: BYL719
BYL719 + Letrozole

Experimental: Buparlisib + Letrozole
Buparlisib + Letrozole in 120 patients
Drug: BKM120
BKM120 + Letrozole

Placebo Comparator: Placebo + Letrozole
Placebo (of Buparlisib or BYL719 ) with Letrozole in 120 patients
Drug: Placebo
Placebo (of BYL719 or BKM120) + Letrozole

Primary Outcome Measures :
  1. Pathological Complete Response and Objective Response Rate [ Time Frame: After 24 weeks of treatment ]
    Measure Pathological complete Response after 24 weeks of treatment and Objective response rate according to RECIST 1.1 after 24 weeks of treatment

Secondary Outcome Measures :
  1. Objective response rate according to RECIST 1.1 criteria [ Time Frame: After 24 weeks of treatment ]
    pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment

  2. Frequency and severity, of AEs and lab abnormalities [ Time Frame: During 24 weeks of treatment ]
    To evaluate the safety and tolerability of study treatment based on the frequency, severity AEs, lab abnormalities

  3. Rate breast conserving surgery [ Time Frame: After 24 weeks of treatment ]
    Rate of breast conserving surgery, following completion of 24 weeks of treatment

  4. Molecular markers and correlation with response [ Time Frame: Baseline, Day 15 and 24 weeks of treatment ]
    Correlation between pCR and change in Ki67 from baseline to day 15 and baseline to surgery

  5. PEPI (preoperative endocrine prognostic index) score [ Time Frame: After 24 weeks of treatment ]
    To assess the Preoperative endocrine prognostic index (PEPI) score after 24 weeks of treatment

  6. Plasma concentration of BYL719/buparlisib and letrozole when given in combination [ Time Frame: Cycle 1 (Day 1, 2, 8, 15, 22), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4(Day 1 and Day 2), Cycle 5 Day 1 and Cycle 6 Day 1 ]
    Plasma concentration time profiles of BYL719/buparlisib and appropriate individual PK parameters Plasma concentration time profiles of letrozole and appropriate individual PK parameters

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

Inclusion Criteria:

  1. Patient is an adult, female ≥ 18 years old at the time of informed consent
  2. Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer
  3. Patient is postmenopausal.
  4. Patient has T1c-T3, any N, M0, operable breast cancer
  5. Patients must have measurable disease
  6. Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
  7. Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
  8. Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing

Exclusion Criteria:

  1. Patient has locally recurrent or metastatic disease
  2. Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before randomization.
  3. Patient with type 1 diabetes mellitus or not adequately controlled type 2 diabetes mellitus
  4. History of acute pancreatitis within 1 year of study entry
  5. Uncontrolled hypertension
  6. Other protocol-defined inclusion/exclusion criteria may apply

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 identifier (NCT number): NCT01923168

  Hide Study Locations
United States, Alabama
University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI
Birmingham, Alabama, United States, 35294-0006
United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72703
United States, California
Los Angeles Hematology/Oncology Medical Group Onc Dept.
Los Angeles, California, United States, 90017
University of California at Los Angeles UCLA SC
Los Angeles, California, United States, 90095
University of California San Francisco BYL719A2201 - SC
San Francisco, California, United States, 94115
United States, Georgia
Emory University School of Medicine/Winship Cancer Institute SC
Atlanta, Georgia, United States, 30322
United States, Maryland
Mercy Medical Center Medical Oncology & Hematology
Baltimore, Maryland, United States, 21202
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Johns Hopkins Med. BYL719A2201
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana Farber Cancer Institute BYL719A2201
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic - Rochester BYL719A2201 - SC
Rochester, Minnesota, United States, 55905
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, North Carolina
Duke University Medical Center Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oregon
Northwest Cancer Specialists Vancouver Loc
Portland, Oregon, United States, 97210
United States, Tennessee
Vanderbilt Ingram Cancer Center Vanderbilt Health 100 Oaks
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology, P.A.
Bedford, Texas, United States, 76022
Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp
Dallas, Texas, United States, 75231
Texas Oncology Texas Oncology - Sammons
Dallas, Texas, United States, 75246
Texas Oncology Houston Memorial City SC
Houston, Texas, United States, 77024
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
San Antonio, Texas, United States, 78229
Cancer Therapy & Research Center UT Health Science Center InstituteForDrugDevelopment(5)
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Oncology Associates SC
Norfolk, Virginia, United States, 23502
United States, Washington
Seattle Cancer Care Alliance SC-3
Seattle, Washington, United States, 98105
Northwest Medical Specialties Dept.ofNW Med. Specialties
Tacoma, Washington, United States, 98405
Australia, New South Wales
Novartis Investigative Site
Kingswood, New South Wales, Australia, 2747
Novartis Investigative Site
Innsbruck, Tyrol, Austria, 6020
Novartis Investigative Site
Dornbirn, Vorarlberg, Austria, 6830
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Leoben, Austria, A-8700
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Rankweil, Austria, A-6830
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Salzburg, Austria, 5020
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Vienna, Austria, A-1090
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Villach, Austria, 9500
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Wien, Austria, A-1090
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Edegem, Antwerpen, Belgium, 2650
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Leuven, Belgium, 3000
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Sint Niklaas, Belgium, 9100
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Goiania, GO, Brazil, 74605-070
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Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
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Ribeirao Preto, SP, Brazil, 14048-900
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Sao Paulo, SP, Brazil, 01317-002
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Sao Paulo, SP, Brazil, 03102-002
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Shumen, Bulgaria, 9700
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Sofia, Bulgaria, 1303
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Varna, Bulgaria, 9010
Canada, British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Quebec
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Montreal, Quebec, Canada, H2W 1T8
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Montreal, Quebec, Canada, H3T 1E2
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Quebec, Canada, G1S 4L8
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Medellin, Antioquia, Colombia
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Bogota, Colombia
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Olomouc, CZE, Czechia, 775 20
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Praha, Czechia, 12808
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Berlin, Germany, 13125
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Erlangen, Germany, 91054
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Essen, Germany, 45136
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Kiel, Germany, 24105
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Koeln, Germany, 51067
Hong Kong
Novartis Investigative Site
Hong Kong SAR, Hong Kong
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Haifa, Israel, 3525408
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Ramat Gan, Israel, 5265601
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Tel Aviv, Israel, 64239
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Brescia, BS, Italy, 25127
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Cremona, CR, Italy, 26100
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Macerata, MC, Italy, 62100
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Milano, MI, Italy, 20141
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Napoli, Italy, 80131
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Nagoya-city, Aichi, Japan, 467-8602
Novartis Investigative Site
Hiroshima-city, Hiroshima, Japan, 730-8518
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Osaka-city, Osaka, Japan, 540-0006
Novartis Investigative Site
Bunkyo-ku, Tokyo, Japan, 113-8677
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Koto-ku, Tokyo, Japan, 135-8550
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Niigata, Japan, 951-8566
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Ashrafieh, Lebanon, 166830
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Beirut, Lebanon
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Saida, Lebanon, 652
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Delft, Netherlands, 2625 AD
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Den Haag, Netherlands, 2545 CH
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Leiden, Netherlands, 2300 RC
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Tilburg, Netherlands, 5022 GC
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Sevilla, Andalucia, Spain, 41017
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Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
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Valencia, Comunidad Valenciana, Spain, 46010
Novartis Investigative Site
La Coruna, Galicia, Spain, 15006
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San Sebastián, Pais Vasco, Spain, 20014
Novartis Investigative Site
Madrid, Spain, 28007
Novartis Investigative Site
Madrid, Spain, 28040
Novartis Investigative Site
Madrid, Spain, 28050
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01923168     History of Changes
Other Study ID Numbers: CBYL719A2201
First Posted: August 15, 2013    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Breast Cancer, Pathological Complete Response, neoadjuvant, hormone receptor-positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs