A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
- Conditions
- Prostatic Neoplasms
- Interventions
- Registration Number
- NCT03767244
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to determine if treatment with apalutamide plus androgen deprivation therapy (ADT) before and after radical prostatectomy (RP) with pelvic lymph node dissection (pLND) in participants with high-risk localized or locally advanced prostate cancer results in an improvement in pathological complete response (pCR) rate and metastasis-free survival (MFS) as compared to placebo plus ADT.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 2517
- Histologically confirmed adenocarcinoma of the prostate
- High-risk disease defined by a total Gleason Sum Score greater than equal to (>=) 4+3 (=Grade Groups [GG] 3 5) and >=1 of the following 4 criteria: a) Any combination of Gleason Score 4+3 (= 3) and Gleason Score 8 (4+4 or 5+3) in >= 6 systematic cores (with >=1 core Gleason Score 8 [4+4 or 5+3] included); b) Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in >=3 systematic cores and Prostate-specific antigen (PSA) >=20 ng/mL (with >= 1 core Gleason Score 8 [4+4 or 5+3] included); c) Gleason Score >=9 (=GG 5) in at least 1 systematic or targeted core; d) At least 2 systematic or targeted cores with continuous Gleason Score >=8 (=GG 4), each with > 80 percent (%) involvement
- Candidate for radical prostatectomy with pelvic lymph node dissection as per the investigator
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Contraceptive use by male participants (and female partners of male participants enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
- Able to receive androgen deprivation therapy (ADT) for at least 13 months
- Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Participants are considered eligible only if the central radiological review confirms clinical stage M0
- (a) Prior treatment with androgen receptor antagonists; (b) Treatment with gonadotropin-releasing hormone analog (GnRHa) prior to informed consent form (ICF) signature
- History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer
- Use of any investigational agent less than or equals to (<=)4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time
- Major surgery <=4 weeks prior to randomization
- Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Apalutamide + ADT Androgen Deprivation Therapy (ADT) Participants will receive androgen deprivation therapy (ADT) plus oral administration of apalutamide 240 milligram (mg) (4 tablets of 60 mg each) daily in each cycle (each cycle of 28 days). Participants will receive six cycles of treatment, followed by radical prostatectomy (RP) with pelvic lymph node dissection (pLND), followed by an additional six cycles of treatment. Placebo + ADT Androgen Deprivation Therapy (ADT) Participants will receive ADT with oral administration of matching placebo treatment daily in each cycle (each cycle of 28 days). Participants will receive six cycles of placebo treatment, followed by RP with pLND, followed by an additional six cycles of placebo treatment. Placebo + ADT Placebo Participants will receive ADT with oral administration of matching placebo treatment daily in each cycle (each cycle of 28 days). Participants will receive six cycles of placebo treatment, followed by RP with pLND, followed by an additional six cycles of placebo treatment. Apalutamide + ADT Apalutamide Participants will receive androgen deprivation therapy (ADT) plus oral administration of apalutamide 240 milligram (mg) (4 tablets of 60 mg each) daily in each cycle (each cycle of 28 days). Participants will receive six cycles of treatment, followed by radical prostatectomy (RP) with pelvic lymph node dissection (pLND), followed by an additional six cycles of treatment.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Pathologic complete response (pCR) Approximately 4 years pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter.
Metastasis-Free Survival (MFS) Up to 7 years and 5 months MFS is defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Time to Subsequent First Treatments (TTST-1) Up to 7 years and 5 months TTST-1 is defined as the time from randomization to the date of first subsequent therapy.
Prostate Specific Antigen (PSA)-Free Survival Approximately 4 years PSA-free survival with testosterone recovery defined as the time from randomization to the first detectable serum PSA level with recovered testosterone levels after undetectable PSA post-radical prostatectomy with pelvic lymph node dissection or death, whichever occurs first.
Event Free Survival (EFS) Up to 7 years and 5 months EFS defined as time from randomization to any of the following events: biochemical failure (BCF); or local or regional recurrence by BICR or histopathological assessment; or distant metastasis by BICR or histopathological assessment; or death.
Number of Participants with Physical Examinations Abnormalities as a Measure of Safety and Tolerability Up to 30 days after last dose of study drug (Approximately 8 years) Number of participants with physical examinations (including general appearance of the participant, height, weight, and examination of the skin, ears, nose, throat, lungs, heart, abdomen, extremities, musculoskeletal system, lymphatic system, and nervous system) abnormalities will be reported.
Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability Up to 30 days after last dose of study drug (Approximately 8 years) Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.
Number of Participants with Treatment Compliance Rate Up to 30 days after last dose of study drug (Approximately 8 years) Number of participants who are complaint with study treatment will be assessed.
Time to Distant Metastasis (TTDM) Up to 7 years and 5 months TTDM is defined as the time from the date of enrollment until the first date of distant metastasis.
MFS Based on Conventional Imaging Up to 7 years and 5 months MFS based on conventional imaging, defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis on CT/MRI and bone scan by radiology BICR, pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
Number of Participants with No Evidence of Disease (NED) at 4 Years Up to 4 years Number of participants with NED at 4 years will be reported. NED at 4 years is defined as: (a) alive, (b) Undetectable prostate-specific antigen (PSA), (c) No distant metastasis, (d) No local or regional recurrence, (e) No subsequent therapy for prostate cancer, (f) Testosterone recovery to physiological testosterone levels, defined as 200 nanograms per deciliter (ng/dL).
Number of Participants with Vital Signs Abnormalities as a Measure of Safety and Tolerability Up to 30 days after last dose of study drug (Approximately 8 years) Number of participants with vital signs (including body temperature, heart rate, respiratory rate, and blood pressure) abnormalities will be reported.
Trial Locations
- Locations (202)
Oklahoma City VAMC
🇺🇸Oklahoma City, Oklahoma, United States
Omega Medical Research
🇺🇸Warwick, Rhode Island, United States
Urology of Virginia, PLCC
🇺🇸Virginia Beach, Virginia, United States
Austin Health
🇦🇺Heidelberg, Australia
Australian Clinical Trials - SAN Clinic
🇦🇺Wahroonga, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge
🇧🇷Goiania, Brazil
Prostate Cancer Centre
🇨🇦Calgary, Alberta, Canada
Irmandade Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Princess Margaret Cancer Centre University Health Network
🇨🇦Toronto, Ontario, Canada
CHRU Besancon Hopital Jean Minjoz
🇫🇷Besancon Cedex, France
Chu Rennes Hopital Pontchaillou
🇫🇷Rennes Cedex, France
CHRU Tours Hopital Bretonneau
🇫🇷Tours, France
Universitaetsklinikum der RWTH Aachen
🇩🇪Aachen, Germany
Universitaetsklinikum Koelnt
🇩🇪Koeln, Germany
Kliniken Nordoberpfalz, Klinik für Urologie
🇩🇪Weiden/Opf, Germany
Northern Cancer Institute
🇦🇺St Leonards, Australia
Liga Norte Riograndense Contra O Cancer
🇧🇷Natal, Brazil
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
APHP - Hopital Henri Mondor
🇫🇷Créteil, France
Hopital Edouard Herriot - CHU Lyon
🇫🇷Lyon cedex 03, France
Miami Cancer Institute at Baptist Health / Baptist Health Medical Group
🇺🇸Miami, Florida, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Michigan Institute of Urology, PC
🇺🇸Troy, Michigan, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Duke University School of Medicine
🇺🇸Durham, North Carolina, United States
Medication Management LLC
🇺🇸Greensboro, North Carolina, United States
MidLantic Urology
🇺🇸Bala-Cynwyd, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
VA North Texas Health Care System
🇺🇸Dallas, Texas, United States
Virginia Urology
🇺🇸Richmond, Virginia, United States
Epworth Eastern Hospital
🇦🇺Box Hill, Australia
St Vincent s Hospital Sydney
🇦🇺Darlinghurst, Australia
Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda
🇧🇷Ijui, Brazil
Universidade do Estado do Rio de Janeiro - UERJ
🇧🇷Rio de Janeiro, Brazil
Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
🇧🇷Sao Paulo, Brazil
Instituto Do Cancer Brasil
🇧🇷Tres Lagoas, Brazil
Nova Scotia Health Authority
🇨🇦Halifax, Nova Scotia, Canada
Sunnybrook Health Sciences Center
🇨🇦Toronto, Ontario, Canada
University of Southern California
🇺🇸Los Angeles, California, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Cleveland VA Medical Center
🇺🇸Cleveland, Ohio, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Centro Urologico Profesor Bengio
🇦🇷Cordoba, Argentina
Royal Melbourne Hospital
🇦🇺Parkville, Australia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha, Czechia
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
AdventHealth Medical Group Urology of Denver
🇺🇸Denver, Colorado, United States
Colorado Clinical Research
🇺🇸Lakewood, Colorado, United States
Urology Specialists LLC
🇺🇸Hialeah, Florida, United States
Mayo Clinic - Division Of Hematology/oncology
🇺🇸Jacksonville, Florida, United States
Emory University Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Ochsner LSU Health Shreveport - Regional Urology
🇺🇸Shreveport, Louisiana, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Carolina Urology Partners, PLLC
🇺🇸Huntersville, North Carolina, United States
Vancouver Prostate Centre, Gordon and Leslie Diamond Health Care Centre
🇨🇦Vancouver, British Columbia, Canada
London Health Sciences Center
🇨🇦London, Ontario, Canada
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Králove, Czechia
Australian Urology Associates Pty Ltd
🇦🇺Malvern, Australia
University of California Irvine Medical Center Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Stamford Hospital
🇺🇸Stamford, Connecticut, United States
Albany Medical College
🇺🇸Albany, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Greenville Health
🇺🇸Greenville, South Carolina, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
CAMC Memorial Hospital, Charleston Area Medical Center Physicians
🇺🇸Charleston, West Virginia, United States
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma de, Argentina
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Beth Isreal Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Urology Cancer Center, PC
🇺🇸Omaha, Nebraska, United States
Great Lakes Physician PC d/b/a Western New York Urology Associates
🇺🇸Cheektowaga, New York, United States
Ralph H. Johnson Veterans Affairs Medical Center
🇺🇸Charleston, South Carolina, United States
Hospital Aleman
🇦🇷Caba, Argentina
Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
🇦🇷Cordoba, Argentina
Uroclinica
🇦🇷Mendoza, Argentina
Clinica Mayo de UMCB
🇦🇷San Miguel de Tucuman, Argentina
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Associacao Umane
🇧🇷Sao Paulo, Brazil
CHU de Quebec Universite Laval Hopital de l Enfant Jesus
🇨🇦Quebec, Canada
Krajská nemocnice Liberec
🇨🇿Liberec, Czechia
CHU de Nantes hotel Dieu
🇫🇷Nantes, France
CHU de Toulouse - Hôpital Rangueil
🇫🇷Toulouse Cedex 9, France
Asaf Harofe Medical Center
🇮🇱Beer Yaakov, Israel
Thomayerova nemocnice
🇨🇿Praha 4, Czechia
City Clinic Sp. z o.o.
🇵🇱Warszawa, Poland
Dolnoslaskie Centrum Onkologii, Oddzial Chirurgii Onkologicznej II - Urologia
🇵🇱Wroclaw, Poland
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
CHUM - Centre hospitalier universitaire de Montreal
🇨🇦Montreal, Quebec, Canada
Uromedical Center s.r.o.
🇨🇿Olomouc, Czechia
Fakultni nemocnice Plzen, Urologicka klinika
🇨🇿Plzen, Czechia
Clinique de la Croix du Sud
🇫🇷Quint-Fonsegrives, France
Universitatsklinikum Frankfurt
🇩🇪Frankfurt am Main, Germany
Universitätsklinikum des Saarlandes
🇩🇪Homburg/Saar, Germany
Universitatsklinikum Schleswig Holstein Campus Lubeck
🇩🇪Lubeck, Germany
Praxisgemeinschaft f. Onkologie u. Urologie - Germany
🇩🇪Wilhelmshaven, Germany
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Ospedale di Bassano del Grappa
🇮🇹Bassano del Grappa, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
Chiba University Hospital
🇯🇵Chiba, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Japan
Dokkyo Medical University Saitama Medical Center
🇯🇵Koshigaya, Japan
Kitasato University Hospital
🇯🇵Minami-Ku, Japan
Kindai University Hospital
🇯🇵Osaka Sayama shi, Japan
Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
St. Antonius Ziekenhuis (St. Antonius Hospital)
🇳🇱Nieuwegein, Netherlands
Samodzielny Publiczny Wielospecjalistyczny Zaklad Opieki Zdrowotnej Mswia W Bydgoszczy
🇵🇱Bydgoszcz, Poland
University College London
🇬🇧London, United Kingdom
Mid Yorkshire NHS Trust
🇬🇧Wakefield, United Kingdom
CHU d'Angers
🇫🇷Angers, France
Hopital Pellegrin CHU Bordeaux
🇫🇷Bordeaux N/a, France
Institut Mutualiste Montsouris
🇫🇷Paris, France
Städtisches Klinikum Braunschweig gGmbH - Standort Salzdahlumer
🇩🇪Braunschweig, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Prostata zentrum Nordwest
🇩🇪Gronau, Germany
Generale Regionale F. Miulli
🇮🇹Acquaviva delle Fonti, Italy
San Raffaele Turro - Istituto di Ricovero e Cura a Carattere Scientifico
🇮🇹MIlano, Italy
Universita degli Studi di Torino - Azienda Ospedaliero-Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Italy
Hakodate Goryoukaku Hospital
🇯🇵Hakodate, Japan
Hirosaki University Hospital
🇯🇵Hirosaki, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Aso Co.,Ltd Iizuka Hospital
🇯🇵Matsuyama, Japan
Toho University Sakura Medical Center
🇯🇵Sakura, Japan
Yokohama City University Medical Center
🇯🇵Yokohama, Japan
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Catharinaziekenhuis
🇳🇱Eindhoven, Netherlands
Szpital Wojewodzki im Mikolaja Kopernika w Koszalinie
🇵🇱Koszalin, Poland
Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
Hosp Univ A Coruna
🇪🇸A Coruna, Spain
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Inst. Valenciano de Oncologia
🇪🇸Valencia, Spain
Tungs' Taichung MetroHarbor Hospital
🇨🇳Taichung, Taiwan
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Martini-Klinik am Universitätsklinikum Hamburg-Eppendorf Urologie
🇩🇪Hamburg, Germany
Klinikum St. Elisabeth Straubing GmbH
🇩🇪Straubing, Germany
ASST Spedali Civili Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliera Sant Andrea
🇮🇹Roma, Italy
Nagano Municipal Hospital
🇯🇵Nagano, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Yamaguchi University Hospital
🇯🇵Ube, Japan
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Altai Regional Oncology Dispensary
🇷🇺Barnaul, Russian Federation
Chelyabinsk Regional Clinical Center Of Oncology And Nuclear Medicine
🇷🇺Chelyabinsk, Russian Federation
Hertzen Oncology Research Institute
🇷🇺Moscow, Russian Federation
Hosp. de Jerez de La Frontera
🇪🇸Jerez de la Frontera, Spain
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
Kaohsiung Medical University Chung Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Taiwan University Hospital.
🇨🇳Taipei, Taiwan
The Royal Marsden NHS Trust
🇬🇧London, United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust Royal Preston Hospital
🇬🇧Preston, United Kingdom
Praxis Dr. med. Ralf Eckert
🇩🇪Lutherstadt Eisleben, Germany
Rambam Health Care Campus
🇮🇱Haifa, Israel
Tel Aviv University Sackler School of Medicine - Meir Medical Center (MMC)
🇮🇱Kfar Saba, Israel
Policlinico Abano Terme
🇮🇹Abano Terme, Italy
ASL2 Lanciano - Vasto - Chieti - Ospedale 'SS Annunziata' di Chieti
🇮🇹Chieti, Italy
Azienda Ospedaliero Universitaria Careggi
🇮🇹Firenze, Italy
Clinica di Urologia Policlinico di Modena - Universita di Modena e reggio Emilia
🇮🇹Modena, Italy
Universita Campus Bio-Medico di Roma
🇮🇹Roma, Italy
Ospedale Molinette, AO Città della Salute e della Scienza di
🇮🇹Torino, Italy
UOC di Urologia AOU Integrata di Verona - Polo Chirurgico Confortini - Ospedale Borgo Trento
🇮🇹Verona, Italy
Kurume University Hospital
🇯🇵Kurume, Japan
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Pratia MCM Krakow
🇵🇱Krakow, Poland
Moscow City Clinical Hospital # 62
🇷🇺Moscow, Russian Federation
Medical-sanitary unit 'Neftyanik'
🇷🇺Tyumen, Russian Federation
Hosp. Puerta Del Mar
🇪🇸Cadiz, Spain
Hosp. Gral. Univ. de Castellon
🇪🇸Castellón, Spain
Hosp Virgen de La Victoria
🇪🇸Málaga, Spain
Hosp. Clinico Univ. de Valencia
🇪🇸Valencia, Spain
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Chi Mei Medical Center Yong Kang
🇨🇳Tainan, Taiwan
Southmead Hospital
🇬🇧Bristol, United Kingdom
Rabin Medical Center
🇮🇱Petach Tikva, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Ospedale San Raffaele
🇮🇹Milano, Italy
Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara
🇮🇹Novara, Italy
Akita University Hospital
🇯🇵Akita, Japan
Chiba Cancer Center
🇯🇵Chuo-ku, Japan
University of Miyazaki Hospital
🇯🇵Miyazaki, Japan
Osaka International Cancer Institute
🇯🇵Osaka City, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Japan
Iwate Medical University Hospital
🇯🇵Shiwa-gun, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Japan
Canisius-Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Netherlands
Szpital Uniwersytecki NR 1 IM Dr Antoniego Jurasza
🇵🇱Bydgoszcz, Poland
Vologda Regional Oncological Dispensary
🇷🇺Vologda, Russian Federation
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Fund. Hosp. de Manacor
🇪🇸Manacor, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Ninewells Hospital
🇬🇧Dundee, United Kingdom