A Study of Neoadjuvant Letrozole + Taselisib Versus Letrozole + Placebo in Post-Menopausal Women With Breast Cancer (LORELEI)

NCT ID: NCT02273973

Last Updated: 2018-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 334 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-12
• Study Completion Date: 2017-03-13

Brief Summary

This is a two-arm, randomized, double-blind, multicenter, pre-operative study to evaluate the effect of combining letrozole and GDC-0032 (also known as taselisib) versus letrozole and placebo in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 (HER2) untreated, Stage I-III operable breast cancer. Participants will be randomized into one of the two treatment arms with a 1:1 randomization ratio. Letrozole at 2.5 milligrams (mg) will be dosed once daily plus either Taselisib at 4 mg (two 2-mg tablets) or placebo on a 5 days-on/ 2 days-off schedule for a total of 16 weeks.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Letrozole + Placebo

Participants will receive 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.

Group Type: PLACEBO_COMPARATOR

Letrozole

Intervention Type: DRUG

Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.

Placebo

Intervention Type: OTHER

Placebo tablets matched to taselisib formulation will be administered orally daily on 5 days-on/2 days-off schedule for up to 16 weeks.

Letrozole + Taselisib

Participants will receive 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.

Taselisib

Intervention Type: DRUG

Taselisib will be administered orally at 4 mg (two 2 mg tablets) daily.

Interventions

Letrozole

Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.

Intervention Type: DRUG

Placebo

Placebo tablets matched to taselisib formulation will be administered orally daily on 5 days-on/2 days-off schedule for up to 16 weeks.

Intervention Type: OTHER

Taselisib

Taselisib will be administered orally at 4 mg (two 2 mg tablets) daily.

Intervention Type: DRUG

Other Intervention Names

GDC-0032

Eligibility Criteria

Inclusion Criteria

• Female participants
• Postmenopausal status
• Histologically confirmed invasive breast carcinoma, with all of the following characteristics: (i) Primary tumor greater than or equal to (>/=) 2 centimeters (cm) in largest diameter (cT1-3) by MRI; (ii) Stage I to operable Stage III breast cancer; (iii) Documented absence of distant metastases (M0)
• Estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer
• Breast cancer eligible for primary surgery
• Tumor tissue from formalin-fixed paraffin-embedded cores (FFPE) core biopsy of breast primary tumor that is confirmed as evaluable for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation status by central histopathology laboratory
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Fasting glucose less than or equal to (</=) 125 milligrams per deciliter (mg/dL)
• Adequate hematological, renal, and hepatic function
• Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol, in the investigator's judgment

Exclusion Criteria

• Any prior treatment for primary invasive breast cancer
• Participants with cT4 or cN3 stage breast tumors
• Bilateral invasive, multicentric, or metastatic breast cancer
• Participants who have undergone excisional biopsy of primary tumor and/or axillary lymph nodes or sentinel lymph node biopsy
• Type 1 or 2 diabetes requiring antihyperglycemic medication
• Inability or unwillingness to swallow pills
• Malabsorption syndrome or other condition that would interfere with enteric absorption
• History of prior or currently active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis). Any predisposition for gastrointestinal (GI) toxicity requires prior approval from the Medical Monitor.
• Congenital long QT syndrome or QT interval corrected using Fridericia's formula (QTcF) >470 milliseconds (msec)
• Diffusing capacity of the lungs for carbon monoxide (DLCO) <60% of the predicted values
• Clinically significant (i.e., active) cardiovascular disease, uncontrolled hypertension, unstable angina, history of myocardial infarction, cardiac failure class II-IV
• Any contraindication to MRI examination
• Active infection requiring intravenous antibiotics
• Participants requiring any daily supplemental oxygen
• Clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis
• Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the participants at high risk from treatment complications
• Significant traumatic injury within 3 weeks prior to initiation of study treatment
• Major surgical procedure within 4 weeks prior to initiation of study treatment
• Inability to comply with study and follow-up procedures
• History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

SOLTI Breast Cancer Research Group

OTHER

Sponsor Role: collaborator

Breast International Group

OTHER

Sponsor Role: collaborator

Austrian Breast and Colorectal Cancer Group

UNKNOWN

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Breastlink Med Group Inc

Santa Ana, California, United States

MGH Cancer Center

Boston, Massachusetts, United States

MSKCC at Basking Ridge

Basking Ridge, New Jersey, United States

MSKCC @ Commack

Commack, New York, United States

MSKCC @ West Harrison

Harrison, New York, United States

Memorial Sloan-Kettering Cancer Center; Hematology/Oncology

New York, New York, United States

MSKC @ Rockville

Rockville Centre, New York, United States

MD Anderson Cancer Center

Houston, Texas, United States

Kinghorn Cancer Centre; St Vincents Hospital

Darlinghurst, New South Wales, Australia

Newcastle Mater Misericordiae Hospital; Oncology

Waratah, New South Wales, Australia

Victorian Breast and Oncology Care

East Melbourne, Victoria, Australia

Cabrini Medical Centre; Oncology

Malvern, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Lkh-Univ. Klinikum Graz; Klinik Für Gynäkologie

Graz, , Austria

LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie

Graz, , Austria

Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie

Innsbruck, , Austria

Ordensklinikum Linz Barmherzige Schwestern ; Abt. f. Allgemein- und Viszeralchirurgie

Linz, , Austria

Brustzentrum - Ordination Dr. Wette

Saint Veit/Glan, , Austria

Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.

Salzburg, , Austria

Medizinische Universität Wien; Univ.Klinik für Chirurgie - Abt. für Allgemeinchirurgie

Vienna, , Austria

Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie

Vienna, , Austria

Krankenhaus Der Stadt Wien-Hietzing; Abt. Für Gynäkologie U. Geburtshilfe

Vienna, , Austria

Klinikum Kreuzschwestern Wels; Iii. Interne Abt.

Wels, , Austria

Institut Jules Bordet

Brussels, , Belgium

CHU Brugmann (Victor Horta)

Brussels, , Belgium

Cliniques Universitaires St-Luc

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

Clinique Ste-Elisabeth

Namur, , Belgium

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina, Brazil

Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Instituto Brasileiro De Controle Do Câncer - IBCC; Laboratório De Patologia

São Paulo, São Paulo, Brazil

Hospital Clinico Vina del Mar

Viña del Mar, , Chile

Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology

Hradec Králové, , Czechia

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, , Czechia

MULTISCAN, s.r.o., Radiologicke centrum Pardubice

Pardubice, , Czechia

Oblastni nemocnice Pribram

Příbram, , Czechia

Hospital Oncologia; Oncology

San Salvador, , El Salvador

Centre Jean Perrin; Division De Recherche Clinique

Clermont-Ferrand, , France

Centre Jean Bernard

Le Mans, , France

Institut Curie; Oncologie Medicale

Paris, , France

Hopital Saint Louis; Service Onco Thoracique

Paris, , France

Centre Rene Huguenin; ONCOLOGIE GENETIQUE

Saint-Cloud, , France

CHI de Toulon - Hôpital Sainte Musse

Toulon, , France

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)

Berlin, , Germany

Studienzentrum Berlin City

Berlin, , Germany

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, , Germany

Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden

Dresden, , Germany

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum

Essen, , Germany

Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum

Gelsenkirchen, , Germany

Universitätsklinikum Hamburg-Eppendorf (UKE); Klinik und Poliklinik für Gynäkologie

Hamburg, , Germany

Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe

Hanover, , Germany

Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe

Lübeck, , Germany

Rotkreuzklinikum München; Frauenklinik

München, , Germany

Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe

Münster, , Germany

Universitätsklinikum Ulm Am Michelsberg; Frauenklinik

Ulm, , Germany

Marien-Hospital Witten; Frauenklinik Brustzentrum

Witten, , Germany

Centro Oncológico Sixtino / Centro Oncológico SA

Guatemala City, , Guatemala

Grupo Angeles

Guatemala City, , Guatemala

Szent Margit Hospital; Dept. of Oncology

Budapest, , Hungary

Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika

Debrecen, , Hungary

Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont

Kecskemét, , Hungary

B-A-Z County Hospital

Miskolc, , Hungary

Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika

Szeged, , Hungary

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica

Bologna, Emilia-Romagna, Italy

Ospedale degli Infermi

Rimini, Emilia-Romagna, Italy

Uni Degli Studi Di Genova ; Clinica Di Medicina Interna Ad Indirizzo Oncologico

Genoa, Liguria, Italy

ASST DI CREMONA; Dip. Medicina - S.C. Oncologia

Cremona, Lombardy, Italy

Ospedale Per Acuti Mater Salutis Di Legnago

Legnago, Lombardy, Italy

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1

Milan, Lombardy, Italy

Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica

Milan, Lombardy, Italy

Centro Estatal de Cancerología

Chihuahua City, , Mexico

Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios

Distrito Federal, , Mexico

Consultorio de Medicina Especializada; Dentro de Condominio San Francisco

Mexico City, , Mexico

Centro Oncologico America

Panama City, , Panama

Hospital Nacional Cayetano Heredia; Hematology - Oncology

Lima, , Peru

Oncosalud Sac; Oncología

Lima, , Peru

Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional

Lima, , Peru

Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

Gdansk, , Poland

Wojewódzki Szpital Specjalistyczny im. M. Kopernika; Oddział Chemioterapii

Lodz, , Poland

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii

Otwock, , Poland

Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie

Poznan, , Poland

Cent.Onkologii-Instytut im. M. S-Curie, Klinika Now. Piersi i Chirurgii Rekon

Warsaw, , Poland

IPO de Lisboa; Servico de Oncologia Medica

Lisbon, , Portugal

Centro Clinico Champalimaud; Oncologia Medica

Lisbon, , Portugal

IPO do Porto; Servico de Oncologia Medica

Porto, , Portugal

National Cancer Center; Medical Oncology

Gyeonggi-do, , South Korea

Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology

Seoul, , South Korea

Yonsei University Severance Hospital; Medical Oncology

Seoul, , South Korea

Samsung Medical Centre; Division of Hematology/Oncology

Seoul, , South Korea

Hospital Provincial de Castellon; Servicio de Oncologia

Castellon, Castellon, Spain

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, Spain

Instituto Universitario Dexeus; Servicio de Oncología

Barcelona, , Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , Spain

Hospital San Pedro De Alcantara; Servicio de Oncologia

Cáceres, , Spain

Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia

Girona, , Spain

Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia

Jaén, , Spain

Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

Lleida, , Spain

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, , Spain

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, , Spain

Hospital Universitario de Fuenlabrada; Servicio de Oncologia

Madrid, , Spain

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

Hospital Clinico Universitario; Oncologia

Valencia, , Spain

Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

Valencia, , Spain

Fundación IVO

Valencia, , Spain

Kantonsspital Baden; Frauenklinik

Baden, , Switzerland

Kantonsspital Graubünden;Onkologie und Hämatologie

Chur, , Switzerland

Fondazione Oncologia Lago Maggiore

Locarno, , Switzerland

Royal Bournemouth General Hospital; Oncology

Bournemouth, , United Kingdom

Frimley Park Hospital; Breast Resaerch Team

Camberley, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Christie Hospital

Manchester, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Brazil; Chile; Czechia; El Salvador; France; Germany; Guatemala; Hungary; Italy; Mexico; Panama; Peru; Poland; Portugal; South Korea; Spain; Switzerland; United Kingdom

References

Eiger D, Brandao M, de Azambuja E. Lessons learned at SABCS 2019 and to-dos from immunotherapy in breast cancer. ESMO Open. 2020 Mar;5(2):e000688. doi: 10.1136/esmoopen-2020-000688. No abstract available.

Reference Type: DERIVED

PMID: 32188717 (View on PubMed)

Eiger D, Franzoi MA, Ponde N, Brandao M, de Angelis C, Schmitt Nogueira M, de Hemptinne Q, de Azambuja E. Cardiotoxicity of trastuzumab given for 12 months compared to shorter treatment periods: a systematic review and meta-analysis of six clinical trials. ESMO Open. 2020 Feb;5(1):e000659. doi: 10.1136/esmoopen-2019-000659.

Reference Type: DERIVED

PMID: 32079624 (View on PubMed)

Saura C, Hlauschek D, Oliveira M, Zardavas D, Jallitsch-Halper A, de la Pena L, Nuciforo P, Ballestrero A, Dubsky P, Lombard JM, Vuylsteke P, Castaneda CA, Colleoni M, Santos Borges G, Ciruelos E, Fornier M, Boer K, Bardia A, Wilson TR, Stout TJ, Hsu JY, Shi Y, Piccart M, Gnant M, Baselga J, de Azambuja E. Neoadjuvant letrozole plus taselisib versus letrozole plus placebo in postmenopausal women with oestrogen receptor-positive, HER2-negative, early-stage breast cancer (LORELEI): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2019 Sep;20(9):1226-1238. doi: 10.1016/S1470-2045(19)30334-1. Epub 2019 Aug 8.

Reference Type: DERIVED

PMID: 31402321 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-000568-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO28888

Identifier Type: -

Identifier Source: org_study_id