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

NCT01923168 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CBYL719A22012013-001862-41
• Study Type: interventional
• Target: 340
• Locations: 16 countries
• Sites: 85

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.

Conditions

Breast Cancer

Keywords

BYL719; alpelisib; Breast Cancer; BKM120; buparlisib; Pathological Complete Response; neoadjuvant; hormone receptor-positive; HER2 negative; Objective Response Rate

Outcome Measures

Primary Outcomes (4)

• Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort

  Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.

  After 24 weeks of treatment

• Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Wild-type Cohort

  Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.

  After 24 weeks of treatment

• Objective Response Rate Per Investigator Assessment According to RECIST 1.1 for Alpelisib vs. Placebo - PIK3CA Mutant Cohort

  Objective Response Rate (ORR) defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1. BOR was assessed per MRI or Ultrasound and defined as per RECIST 1.1 as CR for a disappearance of all non-nodal target lesions (TL)/non-target lesions (NTL) and a reduction in short axis to \< 10 mm of any pathological lymph nodes assigned as TL/NTL and no new lesion; as PR if not qualifying for CR but with a decrease from baseline ≥ 30% in the sum of diameter of all TL, no progression of NTL and no new lesion.

  After 24 weeks of treatment

• Objective Response Rate According to RECIST 1.1 Per Investigator Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort

  Objective Response Rate (ORR) defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1. BOR was assessed per MRI or Ultrasound and defined as per RECIST 1.1 as CR for a disappearance of all non-nodal target lesions (TL)/non-target lesions (NTL) and a reduction in short axis to \< 10 mm of any pathological lymph nodes assigned as TL/NTL and no new lesion; as PR if not qualifying for CR but with a decrease from baseline ≥ 30% in the sum of diameter of all TL, no progression of NTL and no new lesion.

  After 24 weeks of treatment

Secondary Outcomes (28)

• 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

  After 24 weeks of treatment

• 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

  After 24 weeks of treatment

• Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Mutant Cohort

  After 24 weeks of treatment

• Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort

  After 24 weeks of treatment

• Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR

  Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)

Study Arms (3)

Alpelisib + Letrozole

EXPERIMENTAL

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

Drug: alpelisib

Buparlisib + Letrozole

EXPERIMENTAL

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

Drug: buparlisib

Placebo + Letrozole

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

alpelisib DRUG

BYL719 + Letrozole

Also known as: BYL719

Alpelisib + Letrozole

buparlisib DRUG

BKM120 + Letrozole

Also known as: BKM120

Buparlisib + Letrozole

Placebo DRUG

Placebo (of BYL719 or BKM120) + Letrozole

Also known as: BYL719 Placebo, BKM120 Placebo

Placebo + Letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is an adult, female ≥ 18 years old at the time of informed consent
• Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer
• Patient is postmenopausal.
• Patient has T1c-T3, any N, M0, operable breast cancer
• Patients must have measurable disease
• Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
• Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
• 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

You may not qualify if:

• Patient has locally recurrent or metastatic disease
• Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before randomization.
• Patient with type 1 diabetes mellitus or not adequately controlled type 2 diabetes mellitus
• History of acute pancreatitis within 1 year of study entry
• Uncontrolled hypertension

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (86)

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

Birmingham, Alabama, 35294-0006, United States

Location

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Los Angeles Hematology/Oncology Medical Group Onc Dept.

Los Angeles, California, 90017, United States

Location

University of California at Los Angeles UCLA SC

Los Angeles, California, 90095, United States

Location

University of California San Francisco BYL719A2201 - SC

San Francisco, California, 94115, United States

Location

Emory University School of Medicine/Winship Cancer Institute SC

Atlanta, Georgia, 30322, United States

Location

Mercy Medical Center Medical Oncology & Hematology

Baltimore, Maryland, 21202, United States

Location

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

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute BYL719A2201

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic - Rochester BYL719A2201 - SC

Rochester, Minnesota, 55905, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Duke University Medical Center Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Northwest Cancer Specialists Vancouver Loc

Portland, Oregon, 97210, United States

Location

Vanderbilt Ingram Cancer Center Vanderbilt Health 100 Oaks

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, P.A.

Bedford, Texas, 76022, United States

Location

Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp

Dallas, Texas, 75231, United States

Location

Texas Oncology Texas Oncology - Sammons

Dallas, Texas, 75246, United States

Location

Texas Oncology Houston Memorial City SC

Houston, Texas, 77024, United States

Location

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

San Antonio, Texas, 78229, United States

Location

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

San Antonio, Texas, 78229, United States

Location

Virginia Oncology Associates SC

Norfolk, Virginia, 23502, United States

Location

Seattle Cancer Care Alliance SC-3

Seattle, Washington, 98105, United States

Location

Northwest Medical Specialties Dept.ofNW Med. Specialties

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

Kingswood, New South Wales, 2747, Australia

Location

Novartis Investigative Site

Innsbruck, Tyrol, 6020, Austria

Location

Novartis Investigative Site

Dornbirn, Vorarlberg, 6830, Austria

Location

Novartis Investigative Site

Leoben, A-8700, Austria

Location

Novartis Investigative Site

Rankweil, A-6830, Austria

Location

Novartis Investigative Site

Salzburg, 5020, Austria

Location

Novartis Investigative Site

Vienna, A-1090, Austria

Location

Novartis Investigative Site

Villach, 9500, Austria

Location

Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Sint-Niklaas, 9100, Belgium

Location

Novartis Investigative Site

Goiânia, Goiás, 74605-070, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Novartis Investigative Site

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01317-002, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 03102-002, Brazil

Location

Novartis Investigative Site

Shumen, 9700, Bulgaria

Location

Novartis Investigative Site

Sofia, 1303, Bulgaria

Location

Novartis Investigative Site

Varna, 9010, Bulgaria

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1S 4L8, Canada

Location

Novartis Investigative Site

Medellín, Antioquia, Colombia

Location

Novartis Investigative Site

Bogotá, Colombia

Location

Novartis Investigative Site

Olomouc, CZE, 775 20, Czechia

Location

Novartis Investigative Site

Prague, 12808, Czechia

Location

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Cologne, 51067, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Essen, 45136, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Hong Kong SAR, Hong Kong

Location

Novartis Investigative Site

Haifa, 3525408, Israel

Location

Novartis Investigative Site

Ramat Gan, 5265601, Israel

Location

Novartis Investigative Site

Tel Aviv, 64239, Israel

Location

Novartis Investigative Site

Brescia, BS, 25127, Italy

Location

Novartis Investigative Site

Cremona, CR, 26100, Italy

Location

Novartis Investigative Site

Macerata, MC, 62100, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 467-8602, Japan

Location

Novartis Investigative Site

Hiroshima, Hiroshima, 730-8518, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 540-0006, Japan

Location

Novartis Investigative Site

Bunkyo-ku, Tokyo, 113-8677, Japan

Location

Novartis Investigative Site

Koto-ku, Tokyo, 135 8550, Japan

Location

Novartis Investigative Site

Niigata, 951-8566, Japan

Location

Novartis Investigative Site

Beirut, Lebanon

Location

Novartis Investigative Site

El Achrafiyé, 166830, Lebanon

Location

Novartis Investigative Site

Saida, 652, Lebanon

Location

Novartis Investigative Site

Delft, 2625 AD, Netherlands

Location

Novartis Investigative Site

Leiden, 2300 RC, Netherlands

Location

Novartis Investigative Site

The Hague, 2545 CH, Netherlands

Location

Novartis Investigative Site

Tilburg, 5022 GC, Netherlands

Location

Novartis Investigative Site

Seville, Andalusia, 41017, Spain

Location

Novartis Investigative Site

Donostia / San Sebastian, Basque Country, 20014, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

A Coruña, Galicia, 15006, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Madrid, 28007, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Related Publications (1)

• 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.

  PMID: 30723140 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Alpelisib; NVP-BKM120

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2013
• First Posted: August 15, 2013
• Study Start: March 11, 2014
• Primary Completion: July 7, 2017
• Study Completion: July 8, 2017
• Last Updated: September 14, 2018
• Results First Posted: September 14, 2018

Record last verified: 2018-08

Locations

IT (5); US (23); BR (5); NL (4); CA (4); ES (9); BE (3); DE (5); LE (3); CO (2); BU (3); AU (7); JP (6); CZ (2); HK (1); IL (3)