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

NCT ID: NCT01923168

Last Updated: 2018-09-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-11

Study Completion Date

2017-07-08

Brief Summary

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The purpose of the study was to determine whether treatment with a PI3K inhibitor plus letrozole led to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Alpelisib + Letrozole

Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily.

Group Type EXPERIMENTAL

alpelisib

Intervention Type DRUG

BYL719 + Letrozole

Buparlisib + Letrozole

Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily.

Group Type EXPERIMENTAL

buparlisib

Intervention Type DRUG

BKM120 + Letrozole

Placebo + Letrozole

Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo (of BYL719 or BKM120) + Letrozole

Interventions

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alpelisib

BYL719 + Letrozole

Intervention Type DRUG

buparlisib

BKM120 + Letrozole

Intervention Type DRUG

Placebo

Placebo (of BYL719 or BKM120) + Letrozole

Intervention Type DRUG

Other Intervention Names

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BYL719 BKM120 BYL719 Placebo, BKM120 Placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI

Birmingham, Alabama, United States

Site Status

Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

Los Angeles Hematology/Oncology Medical Group Onc Dept.

Los Angeles, California, United States

Site Status

University of California at Los Angeles UCLA SC

Los Angeles, California, United States

Site Status

University of California San Francisco BYL719A2201 - SC

San Francisco, California, United States

Site Status

Emory University School of Medicine/Winship Cancer Institute SC

Atlanta, Georgia, United States

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Mercy Medical Center Medical Oncology & Hematology

Baltimore, Maryland, United States

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Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Johns Hopkins Med. BYL719A2201

Baltimore, Maryland, United States

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Dana Farber Cancer Institute BYL719A2201

Boston, Massachusetts, United States

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Mayo Clinic - Rochester BYL719A2201 - SC

Rochester, Minnesota, United States

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Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

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Duke University Medical Center Duke University Medical Center

Durham, North Carolina, United States

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Northwest Cancer Specialists Vancouver Loc

Portland, Oregon, United States

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Vanderbilt Ingram Cancer Center Vanderbilt Health 100 Oaks

Nashville, Tennessee, United States

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Texas Oncology, P.A.

Bedford, Texas, United States

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Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp

Dallas, Texas, United States

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Texas Oncology Texas Oncology - Sammons

Dallas, Texas, United States

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Texas Oncology Houston Memorial City SC

Houston, Texas, United States

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Cancer Care Centers of South Texas HOAST CCC of So. TX- San Antonio(2)

San Antonio, Texas, United States

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Cancer Therapy & Research Center UT Health Science Center InstituteForDrugDevelopment(5)

San Antonio, Texas, United States

Site Status

Virginia Oncology Associates SC

Norfolk, Virginia, United States

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Seattle Cancer Care Alliance SC-3

Seattle, Washington, United States

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Northwest Medical Specialties Dept.ofNW Med. Specialties

Tacoma, Washington, United States

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Novartis Investigative Site

Kingswood, New South Wales, Australia

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Novartis Investigative Site

Innsbruck, Tyrol, Austria

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Novartis Investigative Site

Dornbirn, Vorarlberg, Austria

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Novartis Investigative Site

Leoben, , Austria

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Rankweil, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Villach, , Austria

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Edegem, Antwerpen, Belgium

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Leuven, , Belgium

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Sint-Niklaas, , Belgium

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Goiânia, Goiás, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Ribeirão Preto, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Shumen, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Vancouver, British Columbia, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Medellín, Antioquia, Colombia

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Bogotá, , Colombia

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Olomouc, CZE, Czechia

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Prague, , Czechia

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Berlin, , Germany

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Cologne, , Germany

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Erlangen, , Germany

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Essen, , Germany

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Kiel, , Germany

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Hong Kong SAR, , Hong Kong

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Haifa, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Brescia, BS, Italy

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Cremona, CR, Italy

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Macerata, MC, Italy

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Milan, MI, Italy

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Napoli, , Italy

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Nagoya, Aichi-ken, Japan

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Hiroshima, Hiroshima, Japan

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Osaka, Osaka, Japan

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Bunkyo-ku, Tokyo, Japan

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Koto-ku, Tokyo, Japan

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Niigata, , Japan

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Beirut, , Lebanon

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El Achrafiyé, , Lebanon

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Saida, , Lebanon

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Delft, , Netherlands

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Leiden, , Netherlands

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The Hague, , Netherlands

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Tilburg, , Netherlands

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Seville, Andalusia, Spain

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Donostia / San Sebastian, Basque Country, Spain

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Barcelona, Catalonia, Spain

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L'Hospitalet de Llobregat, Catalonia, Spain

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A Coruña, Galicia, Spain

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Valencia, Valencia, Spain

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Novartis Investigative Site

Madrid, , Spain

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Novartis Investigative Site

Madrid, , Spain

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Novartis Investigative Site

Madrid, , Spain

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Countries

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United States Australia Austria Belgium Brazil Bulgaria Canada Colombia Czechia Germany Hong Kong Israel Italy Japan Lebanon Netherlands Spain

References

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Mayer IA, Prat A, Egle D, Blau S, Fidalgo JAP, Gnant M, Fasching PA, Colleoni M, Wolff AC, Winer EP, Singer CF, Hurvitz S, Estevez LG, van Dam PA, Kummel S, Mundhenke C, Holmes F, Babbar N, Charbonnier L, Diaz-Padilla I, Vogl FD, Sellami D, Arteaga CL. A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB). Clin Cancer Res. 2019 May 15;25(10):2975-2987. doi: 10.1158/1078-0432.CCR-18-3160. Epub 2019 Feb 5.

Reference Type DERIVED
PMID: 30723140 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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2013-001862-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBYL719A2201

Identifier Type: -

Identifier Source: org_study_id

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