Phase III Study of DCVAC/PCa Added to Standard Chemotherapy for Men With Metastatic Castration Resistant Prostate Cancer

NCT02111577 | Completed Phase 3 Results DMC

• 2 other identifiers: SP0052012-002814-38
• Study Type: interventional
• Target: 1,182
• Locations: 20 countries
• Sites: 171

Brief Summary

The VIABLE study sought to confirm the hypothesis that the combination of docetaxel with DCVAC/PCa followed by a maintenance therapy with DCVAC/PCa would improve overall survival in patients with metastatic castration-resistant prostate cancer.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Immunotherapy; Metastatic; Castration-resistant; Prostate cancer; Biological; Vaccine

Outcome Measures

Primary Outcomes (1)

• Overall Survival, Intention-to-treat Population

  Overall survival is defined as the time from randomization until death due to any cause.

  From randomization to death due to any cause, up to 58 months

Secondary Outcomes (14)

• Overall Survival, Per Protocol Population

  From randomization to death due to any cause, up to 58 months

• Overall Survival, Intention-to-treat Population, Abiraterone as Prior Therapy

  From randomization to death due to any cause, up to 58 months

• Overall Survival, Intention-to-treat Population, Enzalutamide as Prior Therapy

  From randomization to death due to any cause, up to 58 months

• Overall Survival, Intention-to-treat Population, no Prior Abiraterone or Enzalutamide

  From randomization to death due to any cause, up to 58 months

• Radiological Progression-free Survival, Intention-to-treat Population

  Time from randomization to the date of the earliest objective evidence of either radiographic progression of bone lesions, radiographic progression of soft tissue lesions, or death due to any cause, up to 58 months

Study Arms (2)

DCVAC/PCa with standard of care chemotherapy

EXPERIMENTAL

Combination therapy with DCVAC/PCa and standard of care chemotherapy (docetaxel and prednisone)

Biological: DCVAC/PCa

Placebo with standard of care chemotherapy

PLACEBO COMPARATOR

Combination therapy with placebo and standard of care chemotherapy (docetaxel and prednisone) as comparator

Biological: Placebo

Interventions

DCVAC/PCa BIOLOGICAL

DCVAC/PCa concurrently with docetaxel plus prednisone every 3 weeks (± 7 days). DCVAC/PCa was administered at least 7 days before or and at least 7 days after the nearest chemotherapy (days 8-15 of chemotherapy cycles). After discontinuation of chemotherapy for any reason, each following dose of DCVAC/PCa was given every 4 weeks (-7/+14 days) for up to a total of 15 doses.

Also known as: Stapuldencel

DCVAC/PCa with standard of care chemotherapy

Placebo BIOLOGICAL

Placebo concurrently with docetaxel plus prednisone every 3 weeks (± 7 days). Placebo was administered at least 7 days before or and at least 7 days after the nearest chemotherapy (days 8-15 of chemotherapy cycles). After discontinuation of chemotherapy for any reason, each following dose of placebo was given every 4 weeks (-7/+14 days) for up to a total of 15 doses.

Placebo with standard of care chemotherapy

Eligibility Criteria

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

You may qualify if:

• Male 18 years and older.
• Histologically or cytologically confirmed prostate adenocarcinoma.
• Presence of skeletal, or soft-tissue/visceral/nodal metastases according to one of the following criteria:
• Confirmed pathological fracture related to the disease OR
• Confirmation of distant bone and/or soft-tissue and/or visceral metastases on CT or MRI scan or bone scintigraphy OR
• Positive pathology report of metastatic lesion
• Disease progression despite androgen-deprivation therapy (ADT) as indicated by:
• Prostate-specific antigen (PSA) increase that is ≥ 2 ng/mL and ≥ 25% above the minimum PSA as reached during ADT or above the pre-treatment level, if no response was observed and which is confirmed by a second value 1 or more weeks later OR
• Progression of measurable lymph nodes (short axis ≥ 15 mm) or visceral lesion measurable per RECIST v1.1 criteria, confirmation by an independent review facility (IRF) required OR
• Two or more new lesions appearing on bone scan/imaging compared with a previous scan (confirmation by IRF required)
• Maintenance of castrate conditions: patients, who have not had a surgical orchiectomy, must continue with hormone therapy with gonadotropin releasing hormone/ luteinizing hormone-releasing hormone (GnRH/LHRH) agonists or antagonists to reach levels of serum testosterone of ≤ 1.7 nmol/L (50 ng/dL). The duration of the castration period must be at least 4 months before screening as evidenced by combination of clinical/laboratory data (see section 6.8.1).
• Laboratory criteria:
• White blood cells (WBC) greater than 4,000/mm3 (4.0 x109/L)
• Neutrophil count greater than 1,500/mm3 (1.5 x109/L).
• Hemoglobin of at least 10 g/dL (100 g/L).

You may not qualify if:

• Confirmed brain and/or leptomeningeal metastases (other visceral metastases are acceptable).
• Current symptomatic spinal cord compression requiring surgery or radiation therapy.
• Prior chemotherapy for prostate cancer.
• Patient co-morbidities:
• Subjects who are not indicated for chemotherapy treatment with first line Standard of Care chemotherapy (docetaxel and prednisone).
• HIV positive, human T-lymphotropic virus positive.
• Active hepatitis B (active hepatitis B), active hepatitis C (HCV), active syphilis.
• Evidence of active bacterial, viral or fungal infection requiring systemic treatment.
• Clinically significant cardiovascular disease including:
• symptomatic congestive heart failure.
• unstable angina pectoris.
• serious cardiac arrhythmia requiring medication.
• uncontrolled hypertension.
• myocardial infarction or ventricular arrhythmia or stroke within a 6 months before screening, known left ventricular ejection fraction (LVEF) \< 40% or serious cardiac conduction system disorders, if a pacemaker is not present.
• Pleural and pericardial effusion of any NCI CTCAE grade.

Sponsors & Collaborators

• SOTIO a.s.: lead

Study Sites (177)

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

Location

Ironwood Cancer & Research Centers

Chandler, Arizona, 85224, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259-5499, United States

Location

Compassionate Care Research Group, Inc.

Corona, California, 92879, United States

Location

California Cancer Associates for Research and Excellence

Encinitas, California, 92024, United States

Location

Compassionate Care Research Group, Inc.

Fountain Valley, California, 92708, United States

Location

St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

Hao Wei Zhang, MD, LLC

Los Angeles, California, 90033, United States

Location

Desert Hematology Oncology Medical Group

Rancho Mirage, California, 92270, United States

Location

Compassionate Care Research Group, Inc.

Riverside, California, 92501, United States

Location

Sharp Clinical Oncology Research

San Diego, California, 92123, United States

Location

Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Eastern CT Hematology and Oncololgy Associates

Norwich, Connecticut, 06360, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Univ. of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Saint Luke's Cancer Institute

Kansas City, Kansas, 64111, United States

Location

University of Kansas Cancer Center & Medical Pavilion

Westwood, Kansas, 66205, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Associates In Oncology/Hematology,P.C

Rockville, Maryland, 20850, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Umass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48202, United States

Location

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, 55404, United States

Location

GU Research Network

Omaha, Nebraska, 68130, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Research Centers of Nevada

Henderson, Nevada, 89052, United States

Location

New Jersey Hematology Oncology Associates

Brick, New Jersey, 08724, United States

Location

Premier Urology Associates, LLC / AdvanceMed Research

Lawrenceville, New Jersey, 08648, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

UC Health University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, 97062, United States

Location

Urologic Consultants of Southeastern Pennsylvania

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Cancer Care Associates St. Luke's University and Health Network

Easton, Pennsylvania, 18045, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Associates in Oncology & Hematology

Chattanooga, Tennessee, 37421, United States

Location

Arlington Cancer Center

Arlington, Texas, 76012, United States

Location

UT Health, Internal Medicine, Division of Oncology

Houston, Texas, 77030, United States

Location

Texas Health Physicians Group

Plano, Texas, 75093, United States

Location

Cancer Care Network of South Texas

San Antonio, Texas, 78217, United States

Location

Tyler Hematology Oncology

Tyler, Texas, 75701, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, 22060, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98012, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

West Virginia University Mary Babb Randolph Cancer Center

Morgantown, West Virginia, 26506, United States

Location

Universitatsklinikum fur Urologie und Andrologie

Salzburg, 5020, Austria

Location

Krankenhaus Barmherzige Brueder

Vienna, 1020, Austria

Location

AKH Universitatskrankenhaus Wien

Vienna, 1090, Austria

Location

N.N. Alexandrov National Research Center

Lesnoy, 223040, Belarus

Location

Minsk City Oncological Hospital

Minsk, 220013, Belarus

Location

Clinique d'Oncologie Medicale Institut Jules Bordet

Brussels, 01000, Belgium

Location

Erasme Hospital- Urologie

Brussels, 01070, Belgium

Location

Cliniques Universitaires Saint Luc- Urologie

Brussels, 01200, Belgium

Location

Urologie UZ Gent

Ghent, 09000, Belgium

Location

Urology Department St. Elizabeth Ziekenhuis

Turnhout, 02300, Belgium

Location

Specialized Hospital for Active treatment in Oncology

Haskovo, 6300, Bulgaria

Location

Central Oncology Hospital

Plovdiv, 4000, Bulgaria

Location

Complex Oncology Center

Plovdiv, 4000, Bulgaria

Location

Multifunctional Hospital for Active Treatment Serdika

Sofia, 1303, Bulgaria

Location

Specialized Hospital for Active Treatment of Oncology Diseases

Sofia, 1784, Bulgaria

Location

General Hospital Varazdin

Varaždin, 42000, Croatia

Location

Clinical Hospital Center Zagreb

Zagreb, 10000, Croatia

Location

University Hospital Center Sisters of Charity

Zagreb, 10000, Croatia

Location

Onkologicke centrum, Nemocnice Chomutov

Chomutov, 430 12, Czechia

Location

Klinika onkologie a radioterapie, Fakultni nemocnice

Hradec Králové, 500 05, Czechia

Location

Nemocnice Jihlava, urologicke oddeleni

Jihlava, 586 33, Czechia

Location

Urologicke oddeleni, Krajska nemocnice

Liberec, 46003, Czechia

Location

Onkologicka klinika, Fakultni nemocnice

Olomouc, 775 20, Czechia

Location

Klinika onkologicka, Fakultni nemocnice

Ostrava-Poruba, 708 52, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 100 34, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 12 808, Czechia

Location

Thomayerova nemocnice

Prague, 140 00, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Krajska zdravotni, urologicke oddeleni

Ústí nad Labem, 401 13, Czechia

Location

Rigshospitalet

Copenhagen, 02100, Denmark

Location

St-Louis IDF Medical Oncology

Paris, 75 010, France

Location

Hopital St. Joseph

Paris, 75 014, France

Location

Hospital Cochin, Service de Urologie

Paris, 75014, France

Location

HEGP medical oncology

Paris, 75908, France

Location

HIA Begin

Saint-Mandé, 94160, France

Location

Hospital Civil de Strasbourg

Strasbourg, 67091, France

Location

Charite Universitatsklinikum Berlin

Berlin, 12200, Germany

Location

Stadtisches Klinikum Braunschweig

Braunschweig, 38126, Germany

Location

Klinik und Poliklinik Urologie

Cologne, 50937, Germany

Location

Universtatsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Waldkrankenhaus St. Marien

Erlangen, 91054, Germany

Location

Krankenhaus Nordwest

Frankfurt, 60 439, Germany

Location

Universitatsklinikum Halle (Saale)

Halle, 06120, Germany

Location

Asklepios-Klinik Hamburg-Altona

Hamburg, 22763, Germany

Location

Vinzenkrankenhaus Hannover

Hanover, 30 559, Germany

Location

Medizinische hochschule Hannover

Hanover, 30625, Germany

Location

Universitatskinikum Jena

Jena, 07743, Germany

Location

Universitatsmedizin Mannheim

Mannheim, 68167, Germany

Location

Universtatsklinikum Munster

Münster, 48 149, Germany

Location

Studienpraxis Urologie

Nürtingen, 72622, Germany

Location

Klinikum Oldenburg AOR

Oldenburg, 26133, Germany

Location

Universitastsklinikum Tubingen

Tübingen, 72076, Germany

Location

Universitatsklinikum Ulm

Ulm, 89075, Germany

Location

Ammerland Klinik fur Urologie

Westerstede, 26655, Germany

Location

Praxigemeinschaft fur Onkologie und Urologie

Wilhelmshaven, 26389, Germany

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, H-1062, Hungary

Location

Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointeszet

Budapest, H-1097, Hungary

Location

Bajcsy-Zsilinsky Korhaz

Budapest, H-1106, Hungary

Location

Jasz-Nagykun-Szolnok Megyei

Szolnok, H-5004, Hungary

Location

CRO Aviano

Aviano, Italy

Location

A.O.U. Policlinico Vittorio Emanuele

Catania, 95123, Italy

Location

A.O. Istituti Ospitalieri di Cremona

Cremona, 26100, Italy

Location

A.O. Santa Croce e Carle Oespedale

Cuneo, 12100, Italy

Location

Universita di Roma Sapienza

Rome, 00161, Italy

Location

Azienda Ospedialiera Universitaria Senese

Siena, 53100, Italy

Location

Oncologia medica Ospedale S. Vincenzo

Taormina, 98039, Italy

Location

Paula Stradina Kliniska Universitates slimnica

Riga, LV-1079, Latvia

Location

Lithuanian University of Health Science Oncology Institute

Kaunas, 50009, Lithuania

Location

Klaipeda University Hospital

Klaipėda, 92288, Lithuania

Location

Vilnius University Hospital

Vilnius, 08 661, Lithuania

Location

National Cancer Institute

Vilnius, 08660, Lithuania

Location

VU medical Center

Amsterdam, 1007 MB, Netherlands

Location

Wilhemina Ziekenhuis

Assen, 9401 RK, Netherlands

Location

Tergooi Ziekenhuizen

Hilversum, 1213 XZ, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, 2134 TM, Netherlands

Location

Oncology Medisch Centrum

Leeuwarden, 08934, Netherlands

Location

UMC St.Radboud

Nijmegen, 06525, Netherlands

Location

Oncology Maasstad Ziekenhuis

Rotterdam, 03079, Netherlands

Location

Przychodnia Lekarska (KOMED)

Konin, 62-500, Poland

Location

Szpital im M.Kopernika

Lodz, 93-513, Poland

Location

INSTYTUT im. Marii Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

Centrum Medyczne Ostrobramska

Warsaw, 04-125, Poland

Location

Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego

Wroclaw, 50-556, Poland

Location

Hospital da Luz

Lisbon, 1500-650, Portugal

Location

Centro Hospitalar de Lisboa Norte, E.P.E - Hospital de Santa Maria

Lisbon, 1645-039, Portugal

Location

Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E

Porto, 4200-319, Portugal

Location

CHC Zemun

Belgrade, 11000, Serbia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Institute of Oncology and Radiology of Serbia

Belgrade, 11000, Serbia

Location

KBC Bezanijska Kosa

Belgrade, 11080, Serbia

Location

J.Breza MEDICAL s.r.o.

Bratislava, 851 01, Slovakia

Location

Urologicka ambulancia CUIMED s.r.o.

Bratislava, 851 05, Slovakia

Location

Univerzitna nemocnica Martin

Martin, 036 59, Slovakia

Location

Urologicka ambulancia Uroexam, spol. s r.o.

Nitra, 949 01, Slovakia

Location

UROX s.r.o.

Piešťany, 921 01, Slovakia

Location

Urocentrum MILAB s.r.o.

Prešov, 080 01, Slovakia

Location

Privatna urologicka ambulancia

Trenčín, 911 01, Slovakia

Location

Fakultna nemocnica s poliklinikou Zilina

Žilina, 012 07, Slovakia

Location

Hospital Universitario Príncipe de Asturias

Alcalá de Henares, 28805, Spain

Location

Hospital Clinic I Provincial de Barcelona

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Maranón

Madrid, 28007, Spain

Location

Hosp. Clinico Univ. San Carlos

Madrid, 28040, Spain

Location

Instituto de Investigaciones Sanitarias (IIS), Fundacíon Jimenez Díaz (FJD)

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Centro Integral Oncológico Clara Campal (CIOCC)

Madrid, 28050, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Madrid, 28222, Spain

Location

Hospital Carlos Haya

Málaga, 29010, Spain

Location

Hospital Universitario Quiron Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Örebro University Hospital

Örebrö, SE-701 85, Sweden

Location

University Hospital Umeå, Dept Oncology

Umeå, 901 85, Sweden

Location

The Clatterbridge Cancer Centre

Bebington, CH63 4JY, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

St. Luke's Cancer Centre Royal Surrey County Hospital NHS Foundation Trust

Guildford, GU2 7XX, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Northern Centre for Cancer Care, Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (2)

• Hensler M, Rakova J, Kasikova L, Lanickova T, Pasulka J, Holicek P, Hraska M, Hrnciarova T, Kadlecova P, Schoenenberger A, Sochorova K, Rozkova D, Sojka L, Drozenova J, Laco J, Horvath R, Podrazil M, Hongyan G, Brtnicky T, Halaska MJ, Rob L, Ryska A, Coosemans A, Vergote I, Garg AD, Cibula D, Bartunkova J, Spisek R, Fucikova J. Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines. Oncoimmunology. 2022 Jul 22;11(1):2101596. doi: 10.1080/2162402X.2022.2101596. eCollection 2022.

  PMID: 35898703 DERIVED

• Vogelzang NJ, Beer TM, Gerritsen W, Oudard S, Wiechno P, Kukielka-Budny B, Samal V, Hajek J, Feyerabend S, Khoo V, Stenzl A, Csoszi T, Filipovic Z, Goncalves F, Prokhorov A, Cheung E, Hussain A, Sousa N, Bahl A, Hussain S, Fricke H, Kadlecova P, Scheiner T, Korolkiewicz RP, Bartunkova J, Spisek R; VIABLE Investigators. Efficacy and Safety of Autologous Dendritic Cell-Based Immunotherapy, Docetaxel, and Prednisone vs Placebo in Patients With Metastatic Castration-Resistant Prostate Cancer: The VIABLE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 Apr 1;8(4):546-552. doi: 10.1001/jamaoncol.2021.7298.

  PMID: 35142815 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Prof. Radek Spisek, M.D., Ph.D.
• Organization: SOTIO a.s.

spisek@sotio.com

+420 2241 75101

Study Officials

• Nicholas J. Vogelzang

  US Oncology Research/Comprehensive Cancer Centers of Nevada

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: April 11, 2014
• Study Start: May 26, 2014
• Primary Completion: January 28, 2020
• Study Completion: January 28, 2020
• Last Updated: April 6, 2021
• Results First Posted: April 6, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

HU (4); BU (5); DK (1); SE (2); FR (6); LA (1); LI (4); AU (3); CR (3); GB (9); BE (5); DE (19); IT (7); US (58); NL (7); PL (5); CZ (11); PT (3); SL (8); ES (10)