Clinical trial NCT01923168: Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: BYL719
alpelisib
Breast Cancer
BKM120
buparlisib
Pathological Complete Response
neoadjuvant
hormone receptor-positive
HER2 negative
Objective Response Rate
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-08-15
Enrollment: 340
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort
timeFrame: After 24 weeks of treatment
measure: Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Wild-type Cohort
timeFrame: After 24 weeks of treatment
measure: Objective Response Rate Per Investigator Assessment According to RECIST 1.1 for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
timeFrame: After 24 weeks of treatment
measure: Objective Response Rate According to RECIST 1.1 Per Investigator Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
timeFrame: After 24 weeks of treatment
Secondary outcomes:
measure: pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Mutant Cohort Based on ctDNA
timeFrame: After 24 weeks of treatment
measure: pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Wild-type Cohort Based on ctDNA
timeFrame: After 24 weeks of treatment
measure: Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
timeFrame: After 24 weeks of treatment
measure: Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
timeFrame: After 24 weeks of treatment
measure: Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR
timeFrame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
measure: Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR
timeFrame: Baseline, Cycle 1 Day 15 (each cycle is 28 days ) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
measure: Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Responders as Per pCR
timeFrame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
measure: Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Non-responders as Per pCR
timeFrame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
measure: Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
timeFrame: At the time of surgery (expected after 24 weeks of treatment)
measure: Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
timeFrame: At the time of surgery (expected after 24 weeks of treatment)
measure: Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
timeFrame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
measure: Alpelisib PK Parameter: Cmax at Cycle 1 Day 1
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: Alpelisib and PK Parameter: Tmax at Cycle 1 Day 1
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1
timeFrame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
measure: Alpelisib PK Parameter: Cmax at Cycle 4 Day 1
timeFrame: Cycle 4 Day 1 (each cycle is 28 days)
measure: Alpelisib PK Parameter: Tmax at Cycle 4 Day 1
timeFrame: Cycle 4 Day 1 (each cycle is 28 days)
measure: Letrozole and PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
timeFrame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
measure: Letrozole PK Parameter: Cmax at Cycle 1 Day 1
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: Letrozole PK Parameter: Tmax at Cycle 1 Day 1
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: Letrozole PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1
timeFrame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
measure: Letrozole PK Parameter: Cmax at Cycle 4 Day 1
timeFrame: Cycle 4 Day 1 (each cycle is 28 days)
measure: Letrozole PK Parameter: Tmax at Cycle 4 Day 1
timeFrame: Cycle 4 Day 1 (each cycle is 28 days)
measure: Buparlisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
timeFrame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
measure: Buparlisib PK Parameter: Cmax at Cycle 1 Day 1
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: Buparlisib PK Parameter: Tmax at Cycle 1 Day 1
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: Buparlisib PK Parameter: AUClast at Cycle 4 Day 1
timeFrame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
measure: Buparlisb PK Parameter: Cmax at Cycle 4 Day 1
timeFrame: Cycle 4 Day 1 (each cycle is 28 days)
measure: Buparlisib PK Parameter: Tmax at Cycle 4 Day 1
timeFrame: Cycle 4 Day 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI
state: Alabama
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Los Angeles
country: United States
facility: Los Angeles Hematology/Oncology Medical Group Onc Dept.
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA SC
state: California
city: San Francisco
country: United States
facility: University of California San Francisco BYL719A2201 - SC
state: California
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute SC
state: Georgia
city: Baltimore
country: United States
facility: Mercy Medical Center Medical Oncology & Hematology
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Johns Hopkins Med. BYL719A2201
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute BYL719A2201
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester BYL719A2201 - SC
state: Minnesota
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center Duke University Medical Center
state: North Carolina
city: Portland
country: United States
facility: Northwest Cancer Specialists Vancouver Loc
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center Vanderbilt Health 100 Oaks
state: Tennessee
city: Bedford
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Dallas
country: United States
facility: Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Sammons
state: Texas
city: Houston
country: United States
facility: Texas Oncology Houston Memorial City SC
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas HOAST CCC of So. TX- San Antonio(2)
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center UT Health Science Center InstituteForDrugDevelopment(5)
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates SC
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance SC-3
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties Dept.ofNW Med. Specialties
state: Washington
city: Kingswood
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
state: Tyrol
city: Dornbirn
country: Austria
facility: Novartis Investigative Site
state: Vorarlberg
city: Leoben
country: Austria
facility: Novartis Investigative Site
city: Rankweil
country: Austria
facility: Novartis Investigative Site
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Villach
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
state: Antwerpen
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Sint Niklaas
country: Belgium
facility: Novartis Investigative Site
city: Goiania
country: Brazil
facility: Novartis Investigative Site
state: GO
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: Rio Grande Do Sul
city: Ribeirao Preto
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Shumen
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Hong Kong SAR
country: Hong Kong
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Cremona
country: Italy
facility: Novartis Investigative Site
state: CR
city: Macerata
country: Italy
facility: Novartis Investigative Site
state: MC
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Hiroshima-city
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Niigata
country: Japan
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Saida
country: Lebanon
facility: Novartis Investigative Site
city: Delft
country: Netherlands
facility: Novartis Investigative Site
city: Den Haag
country: Netherlands
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: Tilburg
country: Netherlands
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: San Sebastián
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.