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

NCT02273973 | Completed Phase 2 Results

• 2 other identifiers: GO288882013-000568-28
• Study Type: interventional
• Target: 334
• Locations: 21 countries
• Sites: 112

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

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) Via Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1

  Objective response rate (ORR) was defined as proportion of participants achieving complete response (CR) or partial response (PR). As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

  From Baseline to 16 weeks

• Percentage of Participants With Total Pathologic Complete Response (Total pCR), Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer (AJCC) Staging System

  Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).

  From Baseline to 16 weeks

• Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha (PIK3CA) Mutant (MT) Participants

  ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

  From Baseline to 16 weeks

• Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants

  Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).

  From Baseline to 16 weeks

Secondary Outcomes (14)

• Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants

  From Baseline to 16 weeks

• Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants

  From Baseline to 16 weeks

• Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants

  From Baseline to 16 weeks

• Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants

  From Baseline to 16 weeks

• Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants

  From Baseline to 16 weeks

Study Arms (2)

Letrozole + Placebo

PLACEBO COMPARATOR

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.

Drug: Letrozole; Other: Placebo

Letrozole + Taselisib

EXPERIMENTAL

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.

Drug: Letrozole; Drug: Taselisib

Interventions

Letrozole DRUG

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

Letrozole + Placebo; Letrozole + Taselisib

Placebo 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 + Placebo

Taselisib DRUG

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

Also known as: GDC-0032

Letrozole + Taselisib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead
• SOLTI Breast Cancer Research Group: collaborator
• Breast International Group: collaborator
• Austrian Breast and Colorectal Cancer Group: collaborator

Study Sites (117)

Breastlink Med Group Inc

Santa Ana, California, 92705, United States

Location

MGH Cancer Center

Boston, Massachusetts, 02114, United States

Location

MSKCC at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

MSKCC @ Commack

Commack, New York, 11725, United States

Location

MSKCC @ West Harrison

Harrison, New York, 10604, United States

Location

Memorial Sloan-Kettering Cancer Center; Hematology/Oncology

New York, New York, 10065, United States

Location

MSKC @ Rockville

Rockville Centre, New York, 11570, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Kinghorn Cancer Centre; St Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Newcastle Mater Misericordiae Hospital; Oncology

Waratah, New South Wales, 2298, Australia

Location

Victorian Breast and Oncology Care

East Melbourne, Victoria, Australia

Location

Cabrini Medical Centre; Oncology

Malvern, Victoria, 3144, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Lkh-Univ. Klinikum Graz; Klinik Für Gynäkologie

Graz, 8036, Austria

Location

LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie

Graz, 8036, Austria

Location

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

Innsbruck, 6020, Austria

Location

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

Linz, 4010, Austria

Location

Brustzentrum - Ordination Dr. Wette

Saint Veit/Glan, 9300, Austria

Location

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

Salzburg, 5020, Austria

Location

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

Vienna, 1090, Austria

Location

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

Vienna, 1090, Austria

Location

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

Vienna, 1130, Austria

Location

Klinikum Kreuzschwestern Wels; Iii. Interne Abt.

Wels, 4600, Austria

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

CHU Brugmann (Victor Horta)

Brussels, 1020, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Clinique Ste-Elisabeth

Namur, 5000, Belgium

Location

Hospital Sao Lucas - PUCRS

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

Location

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina, 88301-220, Brazil

Location

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

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

São Paulo, São Paulo, 03102-002, Brazil

Location

Hospital Clinico Vina del Mar

Viña del Mar, 2520612, Chile

Location

Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology

Hradec Králové, 500 05, Czechia

Location

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, 779 00, Czechia

Location

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

Pardubice, 532 03, Czechia

Location

Oblastni nemocnice Pribram

Příbram, 261 01, Czechia

Location

Hospital Oncologia; Oncology

San Salvador, 01101, El Salvador

Location

Centre Jean Perrin; Division De Recherche Clinique

Clermont-Ferrand, 63011, France

Location

Centre Jean Bernard

Le Mans, 72015, France

Location

Institut Curie; Oncologie Medicale

Paris, 75231, France

Location

Hopital Saint Louis; Service Onco Thoracique

Paris, 75475, France

Location

Centre Rene Huguenin; ONCOLOGIE GENETIQUE

Saint-Cloud, 92210, France

Location

CHI de Toulon - Hôpital Sainte Musse

Toulon, 83056, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

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

Berlin, 10367, Germany

Location

Studienzentrum Berlin City

Berlin, 14169, Germany

Location

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, 33604, Germany

Location

Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden

Dresden, 01307, Germany

Location

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

Essen, 45136, Germany

Location

Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum

Gelsenkirchen, 45879, Germany

Location

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

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe

Hanover, 30625, Germany

Location

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

Lübeck, 23538, Germany

Location

Rotkreuzklinikum München; Frauenklinik

München, 80637, Germany

Location

Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe

Münster, 48149, Germany

Location

Universitätsklinikum Ulm Am Michelsberg; Frauenklinik

Ulm, 89075, Germany

Location

Marien-Hospital Witten; Frauenklinik Brustzentrum

Witten, 58452, Germany

Location

Centro Oncológico Sixtino / Centro Oncológico SA

Guatemala City, 01010, Guatemala

Location

Grupo Angeles

Guatemala City, 01015, Guatemala

Location

Szent Margit Hospital; Dept. of Oncology

Budapest, 1032, Hungary

Location

Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika

Debrecen, 4032, Hungary

Location

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

Kecskemét, 6000, Hungary

Location

B-A-Z County Hospital

Miskolc, 3526, Hungary

Location

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

Szeged, 6720, Hungary

Location

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

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale degli Infermi

Rimini, Emilia-Romagna, 47923, Italy

Location

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

Genoa, Liguria, 16132, Italy

Location

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

Cremona, Lombardy, 26100, Italy

Location

Ospedale Per Acuti Mater Salutis Di Legnago

Legnago, Lombardy, 37045, Italy

Location

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

Milan, Lombardy, 20133, Italy

Location

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

Milan, Lombardy, 20141, Italy

Location

Centro Estatal de Cancerología

Chihuahua City, 31000, Mexico

Location

Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios

Distrito Federal, 14000, Mexico

Location

Consultorio de Medicina Especializada; Dentro de Condominio San Francisco

Mexico City, 03100, Mexico

Location

Centro Oncologico America

Panama City, 0834-02723, Panama

Location

Hospital Nacional Cayetano Heredia; Hematology - Oncology

Lima, 31, Peru

Location

Oncosalud Sac; Oncología

Lima, 41, Peru

Location

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

Lima, Lima 41, Peru

Location

Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii

Bydgoszcz, 85-796, Poland

Location

Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

Gdansk, 80-952, Poland

Location

Wojewódzki Szpital Specjalistyczny im. M. Kopernika; Oddział Chemioterapii

Lodz, 93-513, Poland

Location

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

Otwock, 05-400, Poland

Location

Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie

Poznan, 61-866, Poland

Location

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

Warsaw, 02-781, Poland

Location

IPO de Lisboa; Servico de Oncologia Medica

Lisbon, 1099-023, Portugal

Location

Centro Clinico Champalimaud; Oncologia Medica

Lisbon, 1400-038, Portugal

Location

IPO do Porto; Servico de Oncologia Medica

Porto, 4200-072, Portugal

Location

National Cancer Center; Medical Oncology

Gyeonggi-do, 410-769, South Korea

Location

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

Seoul, 03080, South Korea

Location

Yonsei University Severance Hospital; Medical Oncology

Seoul, 120-752, South Korea

Location

Samsung Medical Centre; Division of Hematology/Oncology

Seoul, 135-710, South Korea

Location

Hospital Provincial de Castellon; Servicio de Oncologia

Castellon, Castellon, 12002, Spain

Location

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, 14004, Spain

Location

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

Santiago de Compostela, LA Coruña, 15706, Spain

Location

Instituto Universitario Dexeus; Servicio de Oncología

Barcelona, 08028, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital San Pedro De Alcantara; Servicio de Oncologia

Cáceres, 10003, Spain

Location

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

Girona, 17007, Spain

Location

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

Jaén, 23007, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

Lleida, 25198, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, 28050, Spain

Location

Hospital Universitario de Fuenlabrada; Servicio de Oncologia

Madrid, 28943, Spain

Location

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, 41013, Spain

Location

Hospital Clinico Universitario; Oncologia

Valencia, 46010, Spain

Location

Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

Valencia, 46015, Spain

Location

Fundación IVO

Valencia, 46980, Spain

Location

Kantonsspital Baden; Frauenklinik

Baden, 5405, Switzerland

Location

Kantonsspital Graubünden;Onkologie und Hämatologie

Chur, 7000, Switzerland

Location

Fondazione Oncologia Lago Maggiore

Locarno, 6600, Switzerland

Location

Royal Bournemouth General Hospital; Oncology

Bournemouth, BH7 7DW, United Kingdom

Location

Frimley Park Hospital; Breast Resaerch Team

Camberley, GU16 7UJ, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Christie Hospital

Manchester, M20 3BG, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 32188717 DERIVED

• 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.

  PMID: 32079624 DERIVED

• 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.

  PMID: 31402321 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; 2-(3-(2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo(f)imidazo(1,2-d)(1,4)oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: October 24, 2014
• Study Start: November 12, 2014
• Primary Completion: March 13, 2017
• Study Completion: March 13, 2017
• Last Updated: May 21, 2018
• Results First Posted: May 21, 2018

Record last verified: 2018-04

Locations

DE (13); BE (5); EL (1); ES (17); KR (4); PE (3); ME (3); US (8); AU (10); PL (6); BR (5); GU (2); CH (3); CZ (4); HU (5); FR (7); GB (4); CL (1); PT (3); IT (7); PA (1)