Clinical trial NCT02603432: A Study Of Avelumab In Patients With Locally Advanced Or Metastatic Urothelial Cancer (JAVELIN Bladder 100)
Official title: A PHASE 3, MULTICENTER, MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PARALLEL-ARM STUDY OF AVELUMAB (MSB0010718C) PLUS BEST SUPPORTIVE CARE VERSUS BEST SUPPORTIVE CARE ALONE AS A MAINTENANCE TREATMENT IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC UROTHELIAL CANCER WHOSE DISEASE DID NOT PROGRESS AFTER COMPLETION OF FIRST-LINE PLATINUM-CONTAINING CHEMOTHERAPY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urothelial Cancer
Keywords: Bladder cancer
Urologic neoplasms
urothelial carcinoma
PD-L1
programmed cell death protein
maintenance treatment
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-11-11
Enrollment: 700
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: The main purpose of this study is to compare maintenance treatment with avelumab plus best supportive care (BSC) with BSC alone, to determine if avelumab has an effect on survival in patients with locally advanced or metastatic urothelial cancer that did not worsen during or following completion of first-line chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium
* Stage IV disease at the start of first-line chemotherapy
* Measurable disease (per RECIST v1.1) prior to the start of first-line chemotherapy
* Prior first-line chemotherapy must have consisted of at least 4 cycles and no more than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin
* No evidence of progressive disease following completion of first-line chemotherapy (i.e., ongoing CR, PR, or SD per RECIST v1.1 guidelines )

Exclusion Criteria:

* Prior adjuvant or neoadjuvant systemic therapy within 12 months of randomization
* Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
* Persisting toxicity related to prior therapy (Grade \>1 NCI CTCAE v4.0); however, alopecia, sensory neuropathy (Grade 2 or less), or other (Grade 2 or less) adverse events not constituting a safety risk based on the investigator's judgement are acceptable.
* Patients with known symptomatic central nervous system (CNS) metastases requiring steroids
* Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix, low grade prostate cancer on surveillance without any plans for treatment intervention, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to discontinuation from the study, death or date of censoring, whichever occurred first (for a maximum duration of 41 months)
Secondary outcomes:
measure: Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: From randomization to date of progression of disease, discontinuation from the study, death or date of censoring, whichever occurred first (for a maximum duration of 41 months)
measure: Progression-Free Survival (PFS) as Assessed by Investigator
timeFrame: From randomization to date of progression of disease, discontinuation from the study, death or date of censoring, whichever occurred first (for a maximum duration of 41 months)
measure: Percentage of Participants With Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: From randomization to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (for a maximum duration of 41 months)
measure: Percentage of Participants With Objective Response as Assessed by Investigator
timeFrame: From randomization to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (for a maximum duration of 41 months)
measure: Time to Tumor Response (TTR) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: From the date of randomization to the first documentation of objective response (CR or PR) (for a maximum duration of 41 months)
measure: Time to Tumor Response (TTR) as Assessed by Investigator
timeFrame: From the date of randomization to the first documentation of objective response (CR or PR) (for a maximum duration of 41 months)
measure: Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (for a maximum duration of 41 months)
measure: Duration of Response (DOR) as Assessed by Investigator
timeFrame: First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (for a maximum duration of 41 months)
measure: Percentage of Participants With Disease Control (DC) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: From randomization to PD, death or start of new anti-cancer therapy (for a maximum duration of 41 months)
measure: Percentage of Participants With Disease Control (DC) as Assessed by Investigator
timeFrame: From randomization to PD, death or start of new anti-cancer therapy (for a maximum duration of 41 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
timeFrame: For "Avelumab + Best Supportive Care (BSC)'' group: Day1 up to 90 days after last dose of study drug; for BSC group: Day1 up to 90 days after EOT visit (for a maximum duration of up to approximately 70 months for both groups)
measure: Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3 (G3), Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
timeFrame: For "Avelumab + Best Supportive Care (BSC)'' group: Day1 up to 90 days after last dose of study drug; for BSC group: Day1 up to 90 days after EOT visit (for a maximum duration of up to approximately 70 months for both groups)
measure: Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit
timeFrame: Baseline (Day [D] 1 of Cycle [C] 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7 , EOT visit (for a maximum duration of 41 months) (each cycle=28 days)
measure: Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit
timeFrame: Baseline (Day [D] 1 of Cycle [C] 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7 , EOT visit (for a maximum duration of 41 months) (each cycle=28 days)
measure: Maximum Plasma Concentration (Cmax) of Avelumab
timeFrame: End of avelumab infusion on Day 1 of Cycle 1, 2, 3, 5, 7, 9, 11, 13 and Day 15 of Cycle 1, 2, 3 (each cycle=28 days)
measure: Predose Plasma Concentration (Ctrough) of Avelumab
timeFrame: Pre-dose (0 hour) on Day 1 of Cycle 1, 2, 3, 5, 7, 9, 11, 13 and Day 15 of Cycle 1, 2, 3 (each cycle=28 days)
measure: Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
timeFrame: From randomization up to the 30-Day Follow-up visit (maximum duration of up to approximately 68 months)
measure: Number of ADA Ever Positive Participants For Each Serum of ADA Titers for Avelumab
timeFrame: From randomization up to the 30-Day Follow-up visit (maximum duration of up to approximately 68 months)
measure: Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never Positive and Ever Positive Status
timeFrame: From randomization up to the 30-Day Follow-up visit (maximum duration of up to approximately 68 months)
measure: Number of Participants With Programmed Death Receptor-1 Ligand 1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
timeFrame: Up to 41 months at the time of the analysis
measure: Number of Participants With Cluster of Differentiation 8 (CD8) T Lymphocytes (Cytotoxic T Lymphocytes)
timeFrame: Up to approximately 60 months
measure: Change From Baseline in National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Score at Day 1 of Cycle 6
timeFrame: Baseline, Day 1 of Cycle 6 (1 cycle=28 days)
measure: Time to Deterioration (TTD) Based on National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Disease Related Symptoms-Physical Subscale (DRS-P) Scores
timeFrame: From randomization up to the 90-Day Follow-up Visit (maximum duration of up to 41 months)
measure: Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score at Cycle 6
timeFrame: Baseline, Day 1 of Cycle 6 (1 cycle=28 days)
measure: Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) - Visual Analog Scale (VAS) Score at Cycle 6
timeFrame: Baseline, Day 1 of Cycle 6 (1 cycle=28 days)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Anschutz Cancer Center Pavilion Pharmacy
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Denver, CTO (CTRC)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Cleveland
country: United States
facility: Cleveland Clinic Taussing Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussing Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussing Cancer Center
state: Ohio
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute Infusion Pharmacy
state: Virginia
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Pergamino
country: Argentina
facility: Centro de Investigacion Pergamino S.A.
state: Buenos Aires
city: Caba
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: La Rioja
country: Argentina
facility: GP Diagnostico SRL
city: La Rioja
country: Argentina
facility: Hospital Regional Dr. Enrique Vera Barros
city: La Rioja
country: Argentina
facility: Instituto del Diagnostico
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (Cori)
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: Dubbo
country: Australia
facility: Dubbo Base Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: Ramsay Pharmacy
state: New South Wales
city: Kogarah
country: Australia
facility: St George Private Hospital
state: New South Wales
city: Lismore
country: Australia
facility: Epic Pharmacy
state: New South Wales
city: Lismore
country: Australia
facility: North Coast Radiology St Vincents
state: New South Wales
city: Lismore
country: Australia
facility: Northern Rivers Pathology Service
state: New South Wales
city: Lismore
country: Australia
facility: St Vincent's Pathology Lismore
state: New South Wales
city: Macquarie University
country: Australia
facility: Macquarie Medical Imaging
state: New South Wales
city: Macquarie University
country: Australia
facility: Macquarie University Hospital Pharmacy
state: New South Wales
city: Macquarie University
country: Australia
facility: Macquarie University
state: New South Wales
city: Murwillubah
country: Australia
facility: The Murwillumbah Hospital
state: New South Wales
city: Tweed Heads
country: Australia
facility: The Tweed Hospital Pharmacy Department
state: New South Wales
city: Tweed Heads
country: Australia
facility: The Tweed Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Icon Cancer Care Wesley
state: Queensland
city: Auchenflower
country: Australia
facility: River City Pharmacy
state: Queensland
city: Birtinya
country: Australia
facility: Oncology Pharmacy
state: Queensland
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Chermside
country: Australia
facility: Icon Cancer Care Chermside
state: Queensland
city: Douglas
country: Australia
facility: The Townsville Hospital
state: Queensland
city: Geebung
country: Australia
facility: Slade Health
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Care South Brisbane
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Care
state: Queensland
city: South Brisbane
country: Australia
facility: Integrated Clinical Oncology Network (ICON) Corporate Office
state: Queensland
city: Southport
country: Australia
facility: Icon Cancer Care Southport
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Bedford Park
country: Australia
facility: SA Pharmacy, Level 3 Pharmacy
state: South Australia
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
state: South Australia
city: Kurralta park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Kurralta Park
country: Australia
facility: Cancer Care SA Pty Ltd
state: South Australia
city: Kurralta Park
country: Australia
facility: Icon Cancer Care SA trading as Icon Pharmacy Adelaide
state: South Australia
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Ballarat
country: Australia
facility: BHS Diagnostic Services
state: Victoria
city: Ballarat
country: Australia
facility: Lake Imaging
state: Victoria
city: Ballarat
country: Australia
facility: Ballarat Oncology & Haematology Services
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital - Pharmacy Department, Bulding B, Loading Dock (access via Thames St)
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Box Hill
country: Australia
facility: Eastern Health Clinical School
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: East Bentleigh
country: Australia
facility: Monash Medical Centre
state: Victoria
city: East Bentleigh
country: Australia
facility: Moorabbin Radiology
state: Victoria
city: Wendouree
country: Australia
facility: Ballarat Day Procedure Centre
state: Victoria
city: Wendouree
country: Australia
facility: Ballarat Oncology & Haematology Services
state: Victoria
city: Wendouree
country: Australia
facility: Nova Pharmacy
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Murdoch
country: Australia
facility: St John of God Murdoch Hospital
state: Western Australia
city: Mount Waverley
country: Australia
facility: Slade Health
city: New South Wales
country: Australia
facility: Macquarie Heart
city: Brasschaat
country: Belgium
facility: AZ Klina - Apotheek
city: Brasschaat
country: Belgium
facility: AZ Klina
city: Brussels
country: Belgium
facility: Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Hôpital Erasme
city: Gent
country: Belgium
facility: UZ Gent
city: Ghent
country: Belgium
facility: UZ Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Liège
country: Belgium
facility: CHU de Liège
city: Wilrijk
country: Belgium
facility: GZA Sint-Augustinus
city: Salvador
country: Brazil
facility: Hospital da Bahia
state: BA
city: Salvador
country: Brazil
facility: CENOB Centro de Oncologia da Bahia S/S Ltda. / Oncovida
state: BA
city: Ijui
country: Brazil
facility: ONCOSITE - Centro de Pesquisa Clinica em Oncologia
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Hospital Mãe de Deus/Aesc
state: RIO Grande DO SUL
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Câncer - INCA
state: RJ
city: Ijui
country: Brazil
facility: Associacao Hospital de Caridade Ijui
state: RS
city: Porto Alegre
country: Brazil
facility: Associação Educadora São Carlos - AESC / Hospital Mãe de Deus
state: RS
city: Porto Alegre
country: Brazil
facility: Associação Educadora São Carlos - AESC / Hospital Mãe de Deus - Ambulatório Quimioterapia
state: RS
city: Porto Alegre
country: Brazil
facility: Associação Educadora São Carlos - AESC / Hospital Mãe de Deus - Centro de Abastecimento Farmaceut
state: RS
city: Porto Alegre
country: Brazil
facility: Associação Educadora São Carlos - AESC / Hospital Mãe de Deus - Farmácia Oncológica
state: RS
city: Porto Alegre
country: Brazil
facility: Associação Educadora São Carlos - AESC / Hospital Mãe de Deus
state: RS
city: Porto Alegre
country: Brazil
facility: Uniao Brasileira de Educacao e Assistencia / Hospital Sao Lucas da PUCRS
state: RS
city: Barretos
country: Brazil
facility: Fundação FPio XII Barretos
state: SP
city: Barretos
country: Brazil
facility: Fundação Pio XII Barretos
state: SP
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
state: SP
city: Sao Paulo
country: Brazil
facility: Fundacao Faculdade de Medicina / Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da USP - HCFMUSP
state: SP
city: São José do Rio Preto
country: Brazil
facility: Centro Integrado de Pesquisa Clinica - CIP
state: SP
city: São Paulo
country: Brazil
facility: Sociedade Beneficente de Senhoras Hospital Sírio Libanês
state: SP
city: São Paulo
country: Brazil
facility: Sociedade Beneficente de Senhoras Hospital Sírio Libanês
state: SP
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein - SP
state: SP
city: São Paulo
country: Brazil
facility: Sociedade Beneficente de Senhoras Hospital Sírio Libanês/ Instituo Sirio Libanes de Ensino e Pesqu
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: CHUM - Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
state: Ceska Republika
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv.Anny v Brne
city: Horovice
country: Czechia
facility: Nemocnice Horovice, NH Hospital a.s.
city: Horovice
country: Czechia
facility: Nemocnice Horovice
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital Syd
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Aalborg
country: Denmark
facility: Sygehusapoteket Aalborg
city: Aarhus C
country: Denmark
facility: Aarhus Universitetshospital
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: Aarhus N
country: Denmark
facility: CT-Klinikken A/S
city: Copenhagen OE
country: Denmark
facility: Rigshospitalet, Onkologisk Klinik, afsnit 5073
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Herlev
country: Denmark
facility: Herlev og Gentofte Hospital
city: København Ø
country: Denmark
facility: Klinik for Klinisk Fysiologi,Nuklearmedicin og PET
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Paris
country: France
facility: Groupe hospitalier Pitie Saleptriere
state: Cedex 13
city: Angers Cedex 02
country: France
facility: Institut de cancérologie de l'Ouest - Site Paul Papin
city: Angers
country: France
facility: Institut de cancérologie de l'Ouest - Site Paul Papin
city: Bayonne
country: France
facility: Centre d'Oncologie et de Radiothérapie du Pays-Basque
city: Bayonne
country: France
facility: Clinique CAPIO Belharra
city: BESANCON cedex
country: France
facility: Hôpital Jean Minjoz
city: Besançon
country: France
facility: CHU Besançon - Pharmacie Unite Essais cliniques
city: Besançon
country: France
facility: CHU Besançon
city: CRÉTEIL Cedex
country: France
facility: Hôpital Henri Mondor
city: Hyères
country: France
facility: Hôpital Privé Toulon-Hyères - Clinique Sainte Marguerite
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille cedex
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon cedex 8
country: France
facility: Centre Leon Berard
city: LYON cedex 8
country: France
facility: Centre Léon Berard
city: Marseille cedex 5
country: France
facility: Hopital La Conception
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: Hopital de La Timone
city: Marseille
country: France
facility: Hopital de La Timone
city: Nimes Cedex 9
country: France
facility: CHU Nimes - Institut de Cancerologie du Gard
city: Nimes Cedex 9
country: France
facility: CHU Nimes
city: Nimes
country: France
facility: CHU Nimes - Hopital Caremeau
city: PARIS cedex 13
country: France
facility: Groupe Hospitalier Pitié Salpêtrière
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpêtrière
city: Rennes Cedex
country: France
facility: Centre Eugene Marquis
city: Rouen Cedex 1
country: France
facility: Centre Henri Becquerel
city: Rouen
country: France
facility: CHU de Rouen - Hôpital Charles Nicolle
city: Rouen
country: France
facility: CHU de Rouen
city: Saint Herblain Cedex
country: France
facility: Institut de Cancérologie de l'Ouest - Centre René Gauducheau
city: Strasbourg
country: France
facility: Centre de Radiothérapie - Clinique Sainte Anne
city: Strasbourg
country: France
facility: Clinique Sainte Anne
city: Suresnes
country: France
facility: Hopital Foch -Pharmacie
city: Suresnes
country: France
facility: Hopital Foch
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Marousi
country: Greece
facility: Medical Center of Athens
state: Athens
city: Athens
country: Greece
facility: Metropolitan General Hospital
state: PC
city: Athens
country: Greece
facility: Sotiria General Chest Disease Hospital
city: Athens
country: Greece
facility: Alexandra General Hospital, Oncology Department
city: Patra
country: Greece
facility: University General Hospital of Patras, Division of Oncology
city: Thessaloniki
country: Greece
facility: EUROMEDICA General Clinic of Thessaloniki
city: Hong Kong
country: Hong Kong
facility: Department of Clinical Oncology
city: Kaposvár
country: Hungary
facility: Kaposvári Egyetem Egészségügyi Centrum
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház
city: New Delhi
country: India
facility: Dr Ram Manohar Lohia (RML) Hospital & PGI MER
state: Delhi
city: Ahmedabad
country: India
facility: CIMS Cancer, Care Institute of Medical Sciences, CIMS Hospital
state: Gujarat
city: Pune
country: India
facility: Sahyadri Super Speciality Hospital
state: Maharashtra
city: Hyderabad
country: India
facility: Apollo Hospitals
state: Telangana
city: Kolkata
country: India
facility: Medica Superspecialty hospital
state: WEST Bengal
city: Delhi
country: India
facility: Rajiv Gandhi Cancer Institute And Research Centre
city: Kiryat Hadassah
country: Israel
facility: Hadassah University Hospital
state: Jerusalem
city: Tel-Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
state: Ramat - GAN
city: Beer Yaakov
country: Israel
facility: Assaf Harofe MC
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Ramat - Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Candiolo
country: Italy
facility: Farmacia Ospedaliera
state: (torino)
city: Torrette
country: Italy
facility: AOU Ospedali Riuniti di Ancona
state: Ancona
city: Forli
country: Italy
facility: U.O. Anatomia Patologica
state: Forli-cesena
city: Forli
country: Italy
facility: U.O. Radiologia
state: Forli-cesena
city: Forli
country: Italy
facility: U.O.S. Medicina Nucleare
state: Forli-cesena
city: Meldola
country: Italy
facility: Farmacia Oncologica
state: Forli-cesena
city: Meldola
country: Italy
facility: IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
state: Forli-cesena
city: Genova
country: Italy
facility: U.O.C. Farmacia
state: Genoa
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: Liguria
city: Rozzano
country: Italy
facility: Farmacia Studi Clinici
state: Milan
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Faenza
country: Italy
facility: AUSL della Romagna - RAVENNA, Presidio Ospedaliero di Faenza
state: Ravenna
city: Lugo
country: Italy
facility: Presidio Ospedaliero di Lugo
state: Ravenna
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia - IRCCS Candiolo
state: Torino
city: Arezzo
country: Italy
facility: Farmacia Ospedaliera
city: Arezzo
country: Italy
facility: Presidio Ospedaliero San Donato
city: Aviano (PN)
country: Italy
facility: Centro di Riferimento Oncologico - IRCCS
city: Aviano (PN)
country: Italy
facility: S.O.C. di Farmacia
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico S.Orsola Malpighi
city: Bologna
country: Italy
facility: U.O. Farmacia Clinica - IDS
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Dei Tumori
city: Milan
country: Italy
facility: SC Farmacia
city: Milan
country: Italy
facility: Instituto Europeo di Oncologia
city: Milan
country: Italy
facility: Servizio di Farmacia
city: Naples
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"
city: Naples
country: Italy
facility: UOSC Farmacia
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS Fondazione Giovanni Pascale
city: Napoli
country: Italy
facility: S.C. Farmacia Ospedaliera
city: Pisa
country: Italy
facility: A.O.U. Pisana Ospedale S. Chiara
city: Ravenna
country: Italy
facility: Presidio Ospedaliero di Ravenna
city: Ravenna
country: Italy
facility: Servizio Farmacia Ospedaliera - Farmacia Oncologica
city: Rome
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini_Oncologia Medica
city: Rome
country: Italy
facility: U.O.C. Farmacia
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria di Terni
city: Terni
country: Italy
facility: S.C. Farmacia Interna
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Hirosaki
country: Japan
facility: Hirosaki University School of Medicine & Hospital
state: Aomori
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Ota
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Sapporo,
country: Japan
facility: National Hospital Organization hokkaido Cancer Center
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe-city
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Tsukuba
country: Japan
facility: Tsukuba Medical Center Hospital
state: Ibaraki
city: Shiwa-gun
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Sagamihara
country: Japan
facility: National Hospital Organization Sagamihara National Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Kanagawa cancer center
state: Kanagawa
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Koshigaya
country: Japan
facility: Dokkyo Medical University Saitama Medical Center
state: Saitama
city: Hamamatsu
country: Japan
facility: Hamamatsu University School of Medicine, University Hospital
state: Shizuoka
city: Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
state: Tokyo
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kumamoto
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
city: Niigata
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Osaka
country: Japan
facility: Osaka City University Hospital
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center - Clinical Trial Pharmacy
state: Gyeonggi-do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center Urology center for Prostate Cancer
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital, Clinical Pharmacy
state: Gyeonggido
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggido
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital, Clinical Pharmacy
city: Daejeon
country: Korea, Republic of
facility: Chungnam 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 - Clinical Trial Pharmacy
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center Clinical Trial Pharmacy
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerologia
state: Ciudad DE Mexico
city: Cuautitlan Izcalli
country: Mexico
facility: Phylasis Clinicas Research S. de R.L. de C.V.
state: Estado DE Mexico
city: Leon
country: Mexico
facility: Centro de Investigación Clínica de Leon S.C.
state: Guanajuato
city: León
country: Mexico
facility: Hospital Médica Campestre (Administradora Hospitalaria S.A de C.V.)
state: Guanajuato
city: Arnhem
country: Netherlands
facility: Rijnstate Arnhem
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
city: Haarlem
country: Netherlands
facility: St Apotheek der Haarlemse Ziekenhuizen
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Grafton
country: New Zealand
facility: Auckland City Hospital Pharmacy
state: Auckland
city: Grafton
country: New Zealand
facility: Auckland City Hospital
state: Auckland
city: Auckalnd
country: New Zealand
facility: Slade Health Inward Goods
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Lorenskog
country: Norway
facility: Akershus University Hospital
city: Lorenskog
country: Norway
facility: Sykehusapoteket HF 23 Lørenskog
city: Nordbyhagen
country: Norway
facility: Sykehusapoteket HF 23 Lørenskog
city: Nordbyhagen
country: Norway
facility: Sykehusapoteket Lorenskog
city: Nordbyhagen
country: Norway
facility: Bildediagnostisk avdeling
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Warsaw
country: Poland
facility: Centralny Szpital Kliniczny MSWiA w Warszawie
state: Masovian
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA w Warszawie
state: Masovian
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA
state: Masovian
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli
city: Torun
country: Poland
facility: Lecznice CITOMED Sp. z o.o.
city: Torun
country: Poland
facility: Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu Szpital Obserwacyjno-Zakazny
city: Torun
country: Poland
facility: Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu
city: Torun
country: Poland
facility: Wojewodzki Szpital Zespolony im. L. Rydygiera, Szpital Specjalistyczny dla Dzieci I Doroslych
city: Coimbra
country: Portugal
facility: Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE
city: Coimbra
country: Portugal
facility: Hospital Da Luz Coimbra, SA
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo António dos Capuchos
city: Lisboa
country: Portugal
facility: Hospital CUF Descobertas, SA
city: Porto
country: Portugal
facility: Dr. Campos Costa - Consultório de Tomografia Computorizada, S.A.
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar de São João, EPE
city: Senhora da Hora
country: Portugal
facility: Dr. Campos Costa - Consultório de Tomografia Computorizada, S.A.- Matosinhos
city: Vila Real
country: Portugal
facility: Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE
city: Ufa
country: Russian Federation
facility: State Budgetary Healthcare Insti. Republican Clinical Oncology Dispensary of the MoH of Bashk. Rep.
state: Bashkortostan Republic
city: Obninsk
country: Russian Federation
facility: Federal State Budgetary Institution "National medical research radiology center" MoH RF
state: Kaluzhskaya Region
city: Pushkin
country: Russian Federation
facility: Private Medical Institution "Evromedservice"
state: Saint Petersburg
city: Moscow
country: Russian Federation
facility: Principal Military Clinical Hospital n.a. N.N. Burdenko
city: Moscow
country: Russian Federation
facility: Moscow Research Oncology Institute named after P. A. Gertsen
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical oncological dispensary"
city: St. Petersburg
country: Russian Federation
facility: FGBIH "Clinical Hospital #122 n.a. L.G. Sokolov of Federal Medico-biological agency"
city: St. Petersburg
country: Russian Federation
facility: Non-State Healthcare Institution "Railway Clinical Hospital JSC RZhD"
city: St. Petersburg
country: Russian Federation
facility: FSBEI HE "First St. Petersburg State Medical University n. a. academician l.P Pavlov" MoH RF
city: St. Petersburg
country: Russian Federation
facility: FSBEI HE "First St. Petersburg State Medical University n.a. academician I.P Pavlov" MoH RF
city: St. Petersburg
country: Russian Federation
facility: FSBEI HE "First St. Petersburg State Medical University n.a. academician I.P Pavlov"
city: St. Petersburg
country: Russian Federation
facility: "Ramsay Diagnostics Rus", LLC
city: St. Petersburg
country: Russian Federation
facility: FSBI "Russian Scientific Center For Radiology and Surgical Technologies n.a. Academician A.M. Granov
city: St. Petersburg
country: Russian Federation
facility: Hospital Orkli, LLC
city: St. Petersburg
country: Russian Federation
facility: Mart, Llc
city: Yaroslavl
country: Russian Federation
facility: SHI YR "Regional Clinical Oncology Hospital"
city: Belgrade
country: Serbia
facility: Institute for Oncology and Radiology of Serbia
city: Nis
country: Serbia
facility: Clinical Centre Nis, Clinic of Oncology
city: Sremska Kamenica
country: Serbia
facility: Oncology Institute of Vojvodina
city: Santiago de Compostela
country: Spain
facility: C.H. Univ. Santiago de Compostela
state: A Coruña
city: Elda
country: Spain
facility: Hospital Comarcal General de Elda de Virgen de la Salud
state: Alicante
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: l´Hospitalet de LLobregat
country: Spain
facility: Institut Catalá d'Oncología - Hospital Duran i Reynals
state: Barcelona
city: L´Hospitalet de Llobregat
country: Spain
facility: Institut Catalá d'Oncología
state: Barcelona
city: Manresa
country: Spain
facility: Althaia. Xarxa Assistencial Universitaria de Manresa
state: Barcelona
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Comunidad Valenciana
city: Vigo
country: Spain
facility: C. H. Universitario de Vigo- Hospital Álvaro Cunqueiro
state: Galicia
city: Vigo
country: Spain
facility: C. H. Universitario de Vigo- Hospital Álvaro Cunqueiro
state: Galicia
city: Vigo
country: Spain
facility: C.H. Universitario de Vigo- Hospital Meixoeiro
state: Galicia
city: San Sebastian de los Reyes
country: Spain
facility: Hospital Universitario Infanta Sofia
state: Madrid
city: San Sebastián de los Reyes
country: Spain
facility: Hospital Universitario Infanta Sofia
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Alicante
country: Spain
facility: Hospital Vithas Internacional Medimar
city: Badajoz
country: Spain
facility: Hospital Universitario Infanta Cristina
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Quiron of Barcelona
city: Barcelona
country: Spain
facility: Hospital Quiron
city: Barcelona
country: Spain
facility: Hospital Quirón de Barcelona
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant pau_Oncology department
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: CETIR Grup Medic
city: Barcelona
country: Spain
facility: Cetir, Centre Mèdic, S.L
city: Barcelona
country: Spain
facility: Hospital de Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Laboratorio Dr. F. Echevarne Analisis, S.A
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Gerona
country: Spain
facility: H. univ Girona Dr. Josep Trueta - lnstitut Catala d'Oncologia
city: Gerona
country: Spain
facility: Institut Catala d'Oncologia
city: Gerona
country: Spain
facility: Institut Diagnostic de la lmatge
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Fundacion Maria Rafols para la investigacion del Diagnostico de la imagen
city: Madrid
country: Spain
facility: Gabinete Radiologico Doctor Pita
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Madrid
country: Spain
facility: Hospital Ruber International
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro - CIOCC
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Stockholm
country: Sweden
facility: APL
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Taichung
country: Taiwan
facility: Clinical Trial Pharmacy, China Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: Department of Pharmacy, National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Investigational Drug services, National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Taoyuan
country: Taiwan
facility: Chemotherapy pharmacy, Chang Gung Memorial Hospital, Linkou
city: Bath
country: United Kingdom
facility: Royal United Hospitals Bath NHS Foundation Trust
city: London
country: United Kingdom
facility: St Bartholomew 's Hospital, Barts Health NHS Trust
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital, Barts Health NHS Trust
city: London
country: United Kingdom
facility: Guy's & St. Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital, Oxford University Hospitals NHS Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte RJ, Huang B, Costa N, Blake-Haskins JA, Grivas P. Plain language summary of results from the JAVELIN Bladder 100 study: avelumab maintenance treatment for advanced urothelial cancer. Future Oncol. 2022 Jun;18(19):2361-2371. doi: 10.2217/fon-2021-1631. Epub 2022 Apr 13.
citation: Tomita Y, Yamamoto Y, Tsuchiya N, Kanayama H, Eto M, Miyake H, Powles T, Yoshida M, Koide Y, Umeyama Y, di Pietro A, Uemura H. Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis. Int J Clin Oncol. 2022 Feb;27(2):383-395. doi: 10.1007/s10147-021-02067-8. Epub 2022 Jan 1.
citation: Powles T, Sridhar SS, Loriot Y, Bellmunt J, Mu XJ, Ching KA, Pu J, Sternberg CN, Petrylak DP, Tambaro R, Dourthe LM, Alvarez-Fernandez C, Aarts M, di Pietro A, Grivas P, Davis CB. Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial. Nat Med. 2021 Dec;27(12):2200-2211. doi: 10.1038/s41591-021-01579-0. Epub 2021 Dec 10.
citation: Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.