Clinical trial NCT05646862: A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy
Official title: A Phase III, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Versus Alpelisib Plus Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Who Progressed During or After CDK4/6 Inhibitor and Endocrine Combination Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-12-12
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, multicenter, randomized, open-label, global study designed to evaluate the efficacy and safety of inavolisib plus fulvestrant compared with alpelisib plus fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative, PIK3CA-mutated, locally advanced (LA) or metastatic breast cancer (mBC), who progressed during or after cyclin dependent kinase 4/6i (CDK4/6i)-based therapy.


Eligibility criteria: Inclusion Criteria:

* If pre/perimenopausal women and men treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Day 1 of Cycle 1
* Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent
* Documented HR +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
* Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA via specified test
* Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: \<= 2 prior lines of systemic therapy in mBC setting; CDK4/6i based therapy does not need to be the last one received prior study entry; one line of chemotherapy in mBC setting allowed
* Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
* Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* Life expectancy of \> 6 months
* Adequate hematologic and organ function prior to initiation of study treatment

Exclusion Criteria:

* Metaplastic breast cancer
* Prior treatment in locally advanced or metastatic setting with any PI3K, AKT, or mTOR inhibitor or any agent whose mechanism of action is to inhibit the PI3K/-AKT/-mTOR pathway
* Participant who relapsed with documented evidence of progression \> 12 months from completion of adjuvant CDK4/6i based therapy with no treatment for metastatic disease
* Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or at least 60 days after the final dose of study treatment
* Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
* Inability or unwillingness to swallow pills
* Malabsorption syndrome or other condition that would interfere with enteral absorption
* Any history of leptomeningeal disease or carcinomatous meningitis
* Known and untreated, or active central nervous system (CNS) metastases. Participants with a history of treated CNS metastases are eligible if they meet specific certain criteria
* Known active, systemic infection at study enrollment, or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 7 days prior to Day 1 of Cycle 1
* Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition
* Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
* Requirement for daily supplemental oxygen
* Symptomatic active lung disease, including pneumonitis
* History of or active inflammatory bowel disease
* Any active bowel inflammation
* Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis
* Participants with known human immunodeficiency virus infection that meet specific criteria
* Investigational drug(s) within 4 weeks before randomization or within 5 half-lives of the investigational drug(s), whichever is longer
* History of other malignancy within 5 years prior to screening, except for cancers with very low risk of recurrence
* Chronic therapy of \>= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
* Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant, or alpelisib formulations
* History of severe cutaneous reactions like Stevens-Johnson Syndrome, Erythema Multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinphilia and Systemic Symptoms
* Active ongoing osteonecrosis of the jaw

Primary outcomes:
measure: Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)
timeFrame: From randomization until disease progression or death due to any cause (up to approximately 64 months)
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From randomization until death due to any cause (up to approximately 85 months)
measure: BICR-Assessed Overall Response Rate (ORR)
timeFrame: Up to approximately 64 months
measure: BICR-Assessed Best Overall Response (BOR)
timeFrame: Up to approximately 64 months
measure: BICR-Assessed Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 64 months
measure: BICR-Assessed Duration of Response (DOR)
timeFrame: From CR or PR until disease progression or death due to any cause (up to approximately 64 months)
measure: Time to Confirmed Deterioration (TTCD) in Pain
timeFrame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
measure: TTCD in Physical Functioning
timeFrame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
measure: TTCD in Role Functioning
timeFrame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
measure: TTCD in Global Health Status/Quality of Life (QOL)
timeFrame: Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit (up to approximately 85 months). Each cycle is 28 days.
measure: Percentage of Participants with Adverse Events
timeFrame: Day 1 until 30 days after the final dose of study treatment (up to approximately 85 months)
measure: Plasma Concentration of Inavolisib at Specified Timepoints
timeFrame: Day 1 and 15 of Cycle 1, and Day 1 of Cycles 2 and 3. Each cycle is 28 days.
Other outcomes:
Locations:
city: Los Alamitos
country: United States
facility: Cancer Blood and Specialty Clinic
state: California
city: Los Angeles
country: United States
facility: Los Angeles Cancer Network
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Norwich
country: United States
facility: Eastern CT Hematology and Oncology Associates
state: Connecticut
city: Palm Bay
country: United States
facility: Cancer Care Centers of Brevard
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Midtown West Medical
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute at Emory Saint Joseph's Hospital
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute.
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers of Western Michigan
state: Michigan
city: Saint Paul
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Medford
country: United States
facility: Asante Rogue Regional Medical Center
state: Oregon
city: York
country: United States
facility: WellSpan Oncology Research
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology - Dallas Presbyterian Hospital
state: Texas
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro Oncologico Korben
city: La Rioja
country: Argentina
facility: Fundacion CORI para la Investigacion y Prevencion del Cancer
city: Rosario
country: Argentina
facility: Instituto de Oncología de Rosario
city: Rosario
country: Argentina
facility: Sanatorio Parque S.A.
city: Rosario
country: Argentina
facility: Hosp Provincial D. Centenarios
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
city: Viedma
country: Argentina
facility: Clinica Viedma S.A.
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Coffs Harbour Health Campus
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Icon Cancer Care Wesley
state: Queensland
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast
state: Queensland
city: Bendigo
country: Australia
facility: Bendigo Cancer Centre
state: Victoria
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Charleroi
country: Belgium
facility: GHdC Site Les Viviers
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Namur
country: Belgium
facility: Clinique Ste-Elisabeth
city: Salvador
country: Brazil
facility: Hospital da Bahia
state: Bahia
city: Belo Horizonte
country: Brazil
facility: NUPEC
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital Santa Cruz / Centro de Oncologia D'Or
state: Paraná
city: Recife
country: Brazil
facility: Hospital do Cancer de Pernambuco - HCP
state: Pernambuco
city: Recife
country: Brazil
facility: Instituto D?Or de Pesquisa e Ensino ? Hospital Esperança Recife
state: Pernambuco
city: Teresina
country: Brazil
facility: Vencer Oncoclínica - Centro de Pesquisa do Piauí
state: Piauí
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Câncer
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: Rio Grande Do Sul
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Sírio-Libanês
state: São Paulo
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Center-Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer ? Vancouver
state: British Columbia
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l Est de l Ile de Montreal - Hopital Maisonneuve Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hôpital du Sacré-Coeur de Montreal
state: Quebec
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: Sichuan Provincial Cancer Hospital
city: Chongqing
country: China
facility: The First Affiliated Hospital, Chongqing Medical University
city: Guangzhou City
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: Sun yat-sen University Cancer Center
city: Hangzhou City
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
city: Hangzhou City
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University
city: Harbin
country: China
facility: Harbin Medical University Tumor Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Nanchang
country: China
facility: The Second Affiliated Hospital to Nanchang University
city: Nanjing City
country: China
facility: Jiangsu Cancer Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bayonne
country: France
facility: Centre Hospitalier de La Cote Basque
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier cedex 5
country: France
facility: ICM
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Toulouse
country: France
facility: IUCT Oncopole
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen Klinik für Gynäkologie und Geburtsmedizin
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Freiburg
country: Germany
facility: Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
city: Georgsmarienhütte
country: Germany
facility: Niels-Stensen-Kliniken Franziskus-Hospital Harderberg GmbH
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen Georg-August-Universität
city: Hamburg
country: Germany
facility: Mammazentrum Hamburg am Krankenhaus Jerusalem
city: Hannover
country: Germany
facility: Medizinische Hochschule Zentrum Frauenheilkunde Abt.Gynäkologische Onkologie
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT)
city: Mönchengladbach
country: Germany
facility: Brustzentrum Rhein-Ruhr Servicegesellschaft mbH
city: München
country: Germany
facility: Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt
city: Paderborn
country: Germany
facility: St. Vincenz-Krankenhaus GmbH Paderborn Frauen- und Kinderklinik St. Louise
city: Caserta
country: Italy
facility: A.O. S. Anna e San Sebastiano
state: Campania
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
state: Emilia-Romagna
city: Ravenna
country: Italy
facility: AUSL della Romagna
state: Emilia-Romagna
city: Aviano
country: Italy
facility: Irccs Centro Di Riferimento Oncologico (CRO)
state: Friuli-Venezia Giulia
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
city: Macerata
country: Italy
facility: Ospedale Di Macerata
state: Marche
city: Misterbianco (CT)
country: Italy
facility: Humanitas Centro Catanese Di Oncologia
state: Sicilia
city: Empoli (FI)
country: Italy
facility: Ospedale S. Giuseppe
state: Toscana
city: Trento
country: Italy
facility: Ospedale Santa Chiara
state: Trentino-Alto Adige
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Incheon
country: Korea, Republic of
facility: Catholic Univ. of Incheon St.Mary's Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Guadalajara
country: Mexico
facility: Panamerican Clinical Research S.A de C.V.
state: Jalisco
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Ciudad de México
country: Mexico
facility: COI Centro Oncologico Internacional Santa Fe
state: Mexico CITY (federal District)
city: Ciudad de México
country: Mexico
facility: OncoMed
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: ARKE Estudios Clínicos S.A. de C.V.
state: Mexico CITY (federal District)
city: Distrito Federal
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Mexico City
country: Mexico
facility: CENEIT Oncologicos
city: Morelia
country: Mexico
facility: Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
city: Gdynia
country: Poland
facility: Szpital Morski im.PCK
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii Odzia? w Gliwicach
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED, Roman Karaszewski
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Miko?aja Kopernika
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Rzeszow
country: Poland
facility: MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie
city: Durban
country: South Africa
facility: Dr. W.M. Szpak Incorporated trading as Rainbow Oncology
city: Hilton
country: South Africa
facility: Hopelands Cancer Centre
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
city: KwaZulu Natal
country: South Africa
facility: Richards Bay Oncology Centre
city: Paarl
country: South Africa
facility: Mountain View Oncology
city: L Hospitalet De Llobregat
country: Spain
facility: ICO L'Hospitalet
state: Barcelona
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Caceres
country: Spain
facility: Hospital San Pedro De Alcantara
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de Arrixaca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hosipital at Linkou
city: Xitun Dist.
country: Taiwan
facility: Veterans General Hospital - Taichung
city: Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital
city: ChiangMai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Lak Si
country: Thailand
facility: Chulabhorn Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Ankara
country: Turkey
facility: Gulhane Training and Applicaton Hospital
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Diyarbakir
country: Turkey
facility: Dicle University Faculty of Medicine
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Istanbul
country: Turkey
facility: Medipol Mega Üniversite Hastanesi Göztepe
city: Istanbul
country: Turkey
facility: Marmara Uni Faculty of Medicine
city: Izmir
country: Turkey
facility: Ege Uni Medical Faculty Hospital
city: Izmir
country: Turkey
facility: Katip Celebi University Ataturk Training and Research Hospital
city: Kadiköy
country: Turkey
facility: Goztepe Prof.Dr. Suleyman Yalcin City Hospital
city: Seyhan
country: Turkey
facility: Medical Park Seyhan Hospital
city: Sihhiye/Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
city: Dumfries
country: United Kingdom
facility: Dumfries and Galloway Royal Infirmary
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Harlow
country: United Kingdom
facility: Princess Alexandra Hospital
city: Livingston
country: United Kingdom
facility: St John's Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone & Tonbridge Wells Hospital
city: Northwood
country: United Kingdom
facility: Mount Vernon & Watford Trust Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hosptial
city: Winchester
country: United Kingdom
facility: Royal Hampshire County Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: