Perioperative Enfortumab Vedotin (EV) Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Chemotherapy for Cisplatin-Eligible Muscle Invasive Bladder Cancer (MIBC) (MK-3475-B15/ KEYNOTE-B15 / EV-304)

Phase 3

Active, not recruiting

• Conditions: Bladder Cancer
• Interventions: Biological: Pembrolizumab; Biological: Enfortumab vedotin (EV); Drug: Gemcitabine; Procedure: RC + PLND; Drug: Cisplatin

• Registration Number: NCT04700124
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to assess the antitumor efficacy and safety of perioperative enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy \[gemcitabine plus cisplatin\] and RC + PLND) for participants with MIBC who are cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC + PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant gemcitabine + cisplatin and RC + PLND (Arm B).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-05
• Study First Submitted QC: 2021-01-05
• Study First Posted: 2021-01-07
• Study Start: 2021-04-21
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-24
• Primary Completion: 2026-12-23
• Study Completion: 2026-12-23

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 808

Inclusion Criteria

• Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology.
• Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
• Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Have adequate organ function.

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Exclusion Criteria

• Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions
• Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
• Has ≥N2 disease or metastatic disease (M1) as identified by imaging
• Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
• Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
• Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
• Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
• Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
• Has a known psychiatric or substance abuse disorder
• Has had an allogenic tissue/solid organ transplant
• Has ongoing sensory or motor neuropathy Grade 2 or higher
• Has active keratitis (superficial punctate keratitis) or corneal ulcerations
• Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to <8% with associated diabetes symptoms

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND	Enfortumab vedotin (EV)	Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND	RC + PLND	Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND	RC + PLND	Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND	Cisplatin	Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.
Arm B: Standard of Care (SOC)-Neoadjuvant chemotherapy (gemcitabine + cisplatin) and RC + PLND	Gemcitabine	Participants receive 4 cycles (each cycle length = 21 days) of standard of care (SOC) chemotherapy (gemcitabine IV infusion plus cisplatin IV infusion) preoperatively, followed by RC + PLND. The total treatment duration is up to approximately 3 months.
Arm A: Perioperative EV+ Pembrolizumab and RC + PLND	Pembrolizumab	Participants receive 4 cycles (each cycle length = 21 days) of EV intravenous (IV) infusion plus pembrolizumab IV infusion preoperatively, followed by RC + PLND, followed by 5 cycles of adjuvant EV IV infusion plus 13 cycles of adjuvant pembrolizumab IV infusion postoperatively. The total treatment duration is up to approximately 1 year.

Primary Outcome Measures

Name	Time	Method
Event-Free Survival (EFS)	Up to ~68 months	EFS is defined as the time from randomization to the first occurrence of following events: radiographic disease progression precluding RC + PLND, failure to undergo surgery in participants with residual disease, gross residual disease left behind at time of surgery, local or distant recurrence based on blinded independent central review (BICR) or death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Disease Free Survival (DFS)	From ~12 months to up to ~68 months	DFS is defined as the time from postsurgery baseline scan until the first occurrence of either local/distant recurrence as assessed by BICR imaging and/or biopsy or death from any cause.
Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score	Baseline, Up to ~68 months	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Participant responses to questions 29 ("How would you rate your overall health during the past week?") and 30 ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). A higher score indicates a better overall health/quality of life status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined scores will be presented.
Pathologic Complete Response (pCR) Rate	Up to ~47 months	pCR rate is defined as defined as the proportion of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from radical cystectomy (RC) + pelvic lymph node dissection (PLND), as assessed by blinded central pathologic review.
Pathologic Downstaging (pDS) Rate	Up to ~47 months	pDS is defined as participants with \<pT2 (includes pT0, pTis, pTa, and pT1) and N0 in examined tissue from RC plus PLND, based on central pathologic review.
Number of Participants Who Experienced An Adverse Event (AE) (Arm A only)	Up to ~68 months	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be presented.
Change From Baseline in Urinary, Bowel and Sexual Domains per Bladder Cancer Index (BCI)	Baseline, Up to ~68 months	The BCI is a 36-item validated, condition-specific health questionnaire to assess the quality of life among participants with bladder cancer. The BCI contains 3 domains: urinary (14 items), bowel (10 items), and sexual (12 items) with function (Likert response scale: 0 \[Never\] - 4 \[Always\]) and bother (Likert response scale: 0 \[No problem\] - 4 \[Big problem\]) subdomains. The domain and subdomain scores are standardized to a 0 to 100 point scale where higher scores correspond better functioning and health-related qualify of life. The change from baseline in the combined scores of the urinary, bowel, and sexual domains of the BCI will be presented.
Change from Baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS)	Baseline, Up to ~68 months	The EQ-5D-5L VAS records the respondent's self-rated health on a 10 centimeter (cm) vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". The change from baseline in EQ-5D-5L VAS will be presented.
Change from Baseline in EORTC QLQ-C30 Role Functioning Combined Score (Items 6-7)	Baseline, Up to ~68 months	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a better level of role functioning. Change from baseline in the role functioning (EORTC QLQ-C30 Items 6-7) combined score will be presented.
Overall Survival (OS)	Up to ~68 months	OS is defined as the time from randomization to death due to any cause.
Number of Participants Who Discontinued Study Treatment Due to An AE (Arm A only)	Up to ~68 months	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented.
Change from Baseline in EORTC QLQ-C30 Physical Functioning Scale	Baseline, Up to ~68 months	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=not at all to 4=very much). A higher score indicates a better quality of life. The change from baseline in physical function (EORTC QLQ-C30 Items 1-5) score will be presented.
Number of Participants Experiencing Perioperative Complications	Up to ~68 months	Perioperative complications are defined as both intraoperative and postoperative complications, potentially contributing to increased length of inpatient care and/or delay of adjuvant therapy. The number of participants experiencing perioperative complications will be presented.

Trial Locations

Locations (188)

Gifu University Hospital ( Site 1513); 🇯🇵 Gifu, Japan

Volgograd Regional Uronephrological Center ( Site 0870); 🇷🇺 Volzhsky, Volgogradskaya Oblast, Russian Federation

Municipal Non-profit Enterprise of Kharkiv Regional Council RCSDRPP ( Site 0965); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1801); 🇬🇧 London, London, City Of, United Kingdom

UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro; 🇺🇸 Los Angeles, California, United States

Duke University Medical Center ( Site 0017); 🇺🇸 Durham, North Carolina, United States

UT Southwestern Medical Center ( Site 0003); 🇺🇸 Dallas, Texas, United States

Houston Methodist Urology Associates ( Site 0033); 🇺🇸 Houston, Texas, United States

Urology of San Antonio ( Site 0020); 🇺🇸 San Antonio, Texas, United States

Sunway Medical Centre ( Site 0353); 🇲🇾 Petaling Jaya, Selangor, Malaysia

MHAT Serdika ( Site 1152); 🇧🇬 Sofia, Bulgaria

CHU Limoges Hopital Dupuytren ( Site 0459); 🇫🇷 Limoges, Haute-Vienne, France

Complex Oncology Center Plovdiv ( Site 1151); 🇧🇬 Plovdiv, Bulgaria

Klinički bolnički centar Sestre milosrdnice ( Site 1703); 🇭🇷 Zagreb, Grad Zagreb, Croatia

Fundacion Estudios Clinicos-Oncology ( Site 1557); 🇦🇷 Rosario, Santa Fe, Argentina

Fundacion Valle del Lili- CIC ( Site 1656); 🇨🇴 Cali, Valle Del Cauca, Colombia

Centro de Urología (CDU) ( Site 1552); 🇦🇷 Buenos Aires, Argentina

Klinički Bolnički Centar Split-Oncology and Radiotherapy ( Site 1702); 🇭🇷 Split, Splitsko-dalmatinska Zupanija, Croatia

CHU Jean Minjoz ( Site 0453); 🇫🇷 Besancon, Doubs, France

The University of Tennessee Medical Center ( Site 0034); 🇺🇸 Knoxville, Tennessee, United States

UNIVERSITY HOSPITAL OF PATRAS-DIVISION OF ONCOLOGY ( Site 0305); 🇬🇷 Patras, Achaia, Greece

General Hospital of Athens "Alexandra" ( Site 0303); 🇬🇷 Athens, Attiki, Greece

Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 1002); 🇭🇺 Szolnok, Jasz-Nagykun-Szolnok, Hungary

Sheba Medical Center-ONCOLOGY ( Site 0753); 🇮🇱 Ramat Gan, Israel

Hirosaki University Hospital ( Site 1501); 🇯🇵 Hirosaki, Aomori, Japan

University of Tsukuba Hospital ( Site 1502); 🇯🇵 Tsukuba, Ibaraki, Japan

Kitasato University Hospital ( Site 1506); 🇯🇵 Sagamihara, Kanagawa, Japan

Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1057); 🇵🇱 Siedlce, Mazowieckie, Poland

Saint Francis Cancer Center ( Site 0008); 🇺🇸 Greenville, South Carolina, United States

Hospital Británico de Buenos Aires-Oncology ( Site 1551); 🇦🇷 Ciudad autónoma de Buenos Aires, Buenos Aires, Argentina

Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 1558); 🇦🇷 Buenos Aires, Caba, Argentina

Polyclinique du Bois ( Site 0458); 🇫🇷 Lille, Nord, France

Klinički bolnički centar Zagreb-Klinika za onkologiju ( Site 1701); 🇭🇷 Zagreb, Grad Zagreb, Croatia

Klinički bolnički centar Osijek ( Site 1705); 🇭🇷 Osijek, Osjecko-baranjska Zupanija, Croatia

Athens Medical Center ( Site 0304); 🇬🇷 Athens, Attiki, Greece

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ ( Site 1010); 🇭🇺 Szeged, Csongrad, Hungary

Rabin Medical Center-Oncology ( Site 0752); 🇮🇱 Petah-Tikva, Israel

Hadassah Medical Center-Oncology ( Site 0757); 🇮🇱 Jerusalem, Israel

Meir Medical Center-oncology ( Site 0754); 🇮🇱 Kfar Saba, Israel

ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 0301); 🇬🇷 Chaidari, Attiki, Greece

Nagoya University Hospital ( Site 1512); 🇯🇵 Nagoya, Aichi, Japan

Kanagawa Cancer Center ( Site 1507); 🇯🇵 Yokohama, Kanagawa, Japan

University General Hospital of Larissa ( Site 0302); 🇬🇷 Larissa, Thessalia, Greece

Rambam Health Care Campus-Oncology ( Site 0751); 🇮🇱 Haifa, Israel

Kanazawa University Hospital ( Site 1509); 🇯🇵 Kanazawa, Ishikawa, Japan

Hospital Geral de Santo Antonio ( Site 0408); 🇵🇹 Porto, Portugal

Sourasky Medical Center-Oncology ( Site 0755); 🇮🇱 Tel Aviv, Israel

Tohoku University Hospital ( Site 1503); 🇯🇵 Sendai, Miyagi, Japan

Okayama University Hospital ( Site 1516); 🇯🇵 Okayama, Japan

Tokyo Medical and Dental University Hospital ( Site 1505); 🇯🇵 Tokyo, Japan

Institutul Oncologic Cluj-Oncologie Medicala ( Site 1109); 🇷🇴 Cluj, Romania

Chang Gung Memorial Hospital at Kaohsiung ( Site 1203); 🇨🇳 Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan

Keio University Hospital ( Site 1504); 🇯🇵 Tokyo, Japan

Hospital Pulau Pinang ( Site 0355); 🇲🇾 George Town, Pulau Pinang, Malaysia

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu ( Site 1058); 🇵🇱 Wrocław, Dolnoslaskie, Poland

Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1053); 🇵🇱 Przemysl, Podkarpackie, Poland

Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1055); 🇵🇱 Koszalin, Zachodniopomorskie, Poland

Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0409); 🇵🇹 Lisboa, Portugal

Hospital Germans Trias i Pujol. ICO de Badalona ( Site 0658); 🇪🇸 Badalona, Barcelona, Spain

Centro Hospitalar e Universitario de Coimbra ( Site 0406); 🇵🇹 Coimbra, Portugal

Cardiomed SRL Cluj-Napoca ( Site 1101); 🇷🇴 Cluj-Napoca, Cluj, Romania

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1107); 🇷🇴 Craiova, Dolj, Romania

National Medical Research Centre of Oncology named after N.N. Blokhin ( Site 0865); 🇷🇺 Moscow, Moskva, Russian Federation

St.Petersburg Clinical Hospital RAS ( Site 0864); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

St.Petersburg State Medical Univ. n.a. acad. I.P.Pavlov ( Site 0856); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Tan Tock Seng Hospital ( Site 0704); 🇸🇬 Singapore, Central Singapore, Singapore

China Medical University Hospital ( Site 1202); 🇨🇳 Taichung, Taiwan

MI Clinical oncology dispensary of Dnipropetrovsk regional council ( Site 0954); 🇺🇦 Dnipro, Dnipropetrovska Oblast, Ukraine

Torbay Hospital ( Site 1804); 🇬🇧 Torquay, Devon, United Kingdom

Oregon Health and Science University ( Site 0028); 🇺🇸 Portland, Oregon, United States

Mayo Clinic in Arizona - Phoenix ( Site 0043); 🇺🇸 Phoenix, Arizona, United States

University of Colorado, Anschutz Cancer Pavilion ( Site 0009); 🇺🇸 Aurora, Colorado, United States

St Joseph Heritage Healthcare-Oncology ( Site 0035); 🇺🇸 Fullerton, California, United States

University of California San Francisco ( Site 0010); 🇺🇸 San Francisco, California, United States

Stanford University ( Site 0023); 🇺🇸 Stanford, California, United States

University of Iowa Hospital and Clinics ( Site 0029); 🇺🇸 Iowa City, Iowa, United States

White Plains Hospital ( Site 0039); 🇺🇸 White Plains, New York, United States

Indiana University Melvin and Bren Simon Cancer Center ( Site 0050); 🇺🇸 Indianapolis, Indiana, United States

Icahn School of Medicine at Mount Sinai ( Site 0011); 🇺🇸 New York, New York, United States

MidLantic Urology ( Site 0002); 🇺🇸 Bala-Cynwyd, Pennsylvania, United States

Hospital Italiano de Buenos Aires ( Site 1554); 🇦🇷 ABB, Caba, Argentina

Macquarie University-MQ Health Clinical Trials Unit ( Site 1259); 🇦🇺 Macquarie University, New South Wales, Australia

Asociación de Beneficencia Hospital Sirio Libanés ( Site 1553); 🇦🇷 Buenos Aires, Argentina

Lyell McEwin Hospital ( Site 1252); 🇦🇺 Elizabeth Vale, South Australia, Australia

Frankston Hospital-Oncology and Haematology ( Site 1258); 🇦🇺 Frankston, Victoria, Australia

Mater Hospital Brisbane ( Site 1257); 🇦🇺 South Brisbane, Queensland, Australia

MHAT Central Onco Hospital OOD ( Site 1158); 🇧🇬 Plovdiv, Bulgaria

MHAT "Uni Hospital" OOD ( Site 1154); 🇧🇬 Panagyurishte, Pazardzhik, Bulgaria

BC Cancer - Vancouver Center ( Site 0110); 🇨🇦 Vancouver, British Columbia, Canada

Ottawa Hospital Research Institute ( Site 0109); 🇨🇦 Ottawa, Ontario, Canada

Moncton Hospital ( Site 0107); 🇨🇦 Moncton, New Brunswick, Canada

Jewish General Hospital ( Site 0106); 🇨🇦 Montreal, Quebec, Canada

SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1406); 🇨🇳 Guangzhou, Guangdong, China

Hunan Cancer Hospital ( Site 1403); 🇨🇳 Changsha, Hunan, China

Fudan University Shanghai Cancer Center-Urology department ( Site 1401); 🇨🇳 Shanghai, Shanghai, China

Nantong Tumor Hospital-Urology ( Site 1405); 🇨🇳 Nantong, Jiangsu, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University ( Site 1413); 🇨🇳 Guangzhou, Guangdong, China

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S; 🇨🇳 Nanjing, Jiangsu, China

Oncomédica S.A.S ( Site 1652); 🇨🇴 Montería, Cordoba, Colombia

Fundación Colombiana de Cancerología Clínica Vida ( Site 1653); 🇨🇴 Medellin, Antioquia, Colombia

Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1402); 🇨🇳 Shanghai, Shanghai, China

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1654); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Fundación Cardiovascular de Colombia-Santander ( Site 1657); 🇨🇴 Piedecuesta, Santander, Colombia

Fakultni nemocnice u sv. Anny v Brne ( Site 0253); 🇨🇿 Brno, Jihomoravsky Kraj, Czechia

Fakultni nemocnice Hradec Kralove-Klinika onkologie a radioterapie ( Site 0254); 🇨🇿 Hradec Kralove, Czechia

Fakultni Thomayerova nemocnice ( Site 0252); 🇨🇿 Praha 4, Czechia

Fakultni Nemocnice Olomouc ( Site 0251); 🇨🇿 Olomouc, Czechia

CHU La Timone ( Site 0456); 🇫🇷 Marseille, Bouches-du-Rhone, France

Institut Universitaire du Cancer Toulouse - Oncopole ( Site 0455); 🇫🇷 Toulouse, Haute-Garonne, France

CHU de Brest -Site Hopital Morvan ( Site 0461); 🇫🇷 Brest, Finistere, France

Centre Hospitalier Regional du Orleans ( Site 0463); 🇫🇷 Orleans, Loiret, France

Gustave Roussy ( Site 0467); 🇫🇷 Villejuif, Ile-de-France, France

CHU GRENOBLE ALPES ( Site 0468); 🇫🇷 La Tronche, Isere, France

Hopital Diaconesses Croix Saint Simon ( Site 0465); 🇫🇷 Paris, France

Caritas Krankenhaus St. Josef ( Site 0502); 🇩🇪 Regensburg, Bayern, Germany

Universitaetsklinikum Wuerzburg ( Site 0520); 🇩🇪 Wuerzburg, Bayern, Germany

Universitaetsklinik fuer Urologie ( Site 0501); 🇩🇪 Tuebingen, Baden-Wurttemberg, Germany

Vivantes Klinikum Am Urban ( Site 0519); 🇩🇪 Berlin, Germany

Universitaetsklinikum Freiburg ( Site 0512); 🇩🇪 Freiburg, Baden-Wurttemberg, Germany

Krankenhaus Martha Maria Halle-Doelau ( Site 0507); 🇩🇪 Halle, Sachsen-Anhalt, Germany

Universitaetsklinikum Muenster ( Site 0516); 🇩🇪 Muenster, Nordrhein-Westfalen, Germany

Kath. Krankenhaus Marienhospital. Universitaetsklinik ( Site 0511); 🇩🇪 Herne, Nordrhein-Westfalen, Germany

Universitaetsklinikum Carl Gustav Carus ( Site 0509); 🇩🇪 Dresden, Sachsen, Germany

Debreceni Egyetem Klinikai Kozpont ( Site 1006); 🇭🇺 Debrecen, Hungary

Yitzhak Shamir Medical Center-Oncology ( Site 0756); 🇮🇱 Zerifin, Israel

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0588); 🇮🇹 Milan, Lombardia, Italy

Presidio Ospedaliero Santa Maria delle Grazie ( Site 0599); 🇮🇹 Pozzuoli, Napoli, Italy

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento ( Site 0598); 🇮🇹 Verona, Veneto, Italy

AOU San Luigi Gonzaga di Orbassano ( Site 0595); 🇮🇹 Orbassano, Torino, Italy

Azienda Ospedaliero Universitaria delle Marche-Clinica Oncologica ( Site 0593); 🇮🇹 Ancona, Italy

Ospedale Cannizzaro ( Site 0590); 🇮🇹 Catania, Italy

IRCCS Ospedale San Raffaele ( Site 0596); 🇮🇹 Milano, Italy

Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 0600); 🇮🇹 Padova, Italy

Yokohama City University Medical Center ( Site 1508); 🇯🇵 Yokohama, Kanagawa, Japan

Hamamatsu University Hospital ( Site 1511); 🇯🇵 Hamamatsu, Shizuoka, Japan

Nagasaki University Hospital ( Site 1517); 🇯🇵 Nagasaki, Japan

Osaka Metropolitan University Hospital ( Site 1515); 🇯🇵 Osaka, Japan

Osaka International Cancer Institute ( Site 1514); 🇯🇵 Osaka, Japan

Toyama University Hospital ( Site 1510); 🇯🇵 Toyama, Japan

Chonnam National University Hwasun Hospital ( Site 1353); 🇰🇷 Jeollanam-do, Jeonranamdo, Korea, Republic of

Seoul National University Bundang Hospital ( Site 1355); 🇰🇷 Gyeonggi-do, Kyonggi-do, Korea, Republic of

Asan Medical Center ( Site 1352); 🇰🇷 Songpagu, Seoul, Korea, Republic of

Gachon University Gil Medical Center ( Site 1356); 🇰🇷 Incheon, Korea, Republic of

Kyungpook National University Chilgok Hospital ( Site 1354); 🇰🇷 Daegu, Taegu-Kwangyokshi, Korea, Republic of

University Malaya Medical Centre ( Site 0352); 🇲🇾 Lembah Pantai, Kuala Lumpur, Malaysia

THE MEDICAL CITY ILOILO-The Medical City Iloilo - Clinical and Translational Research Institute-Ilo; 🇵🇭 Iloilo City, Iloilo, Philippines

Sarawak General Hospital ( Site 0351); 🇲🇾 Kuching, Sarawak, Malaysia

Narodowy Instytut Onkologii ( Site 1051); 🇵🇱 Warszawa, Mazowieckie, Poland

Clinical Research Center Medic-R ( Site 1061); 🇵🇱 Poznan, Wielkopolskie, Poland

CHLO, EPE - Hospital de Sao Francisco Xavier ( Site 0401); 🇵🇹 Lisboa, Portugal

Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1103); 🇷🇴 Cluj-Napoca, Cluj, Romania

Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1102); 🇷🇴 Cluj Napoca, Cluj, Romania

SC Radiotherapy Center Cluj SRL ( Site 1108); 🇷🇴 Comuna Floresti, Cluj, Romania

SC Focus Lab Plus SRL ( Site 1104); 🇷🇴 Bucuresti, Romania

Policlinica Oncomed SRL ( Site 1106); 🇷🇴 Timisoara, Timis, Romania

Altay Regional Oncology Dispensary ( Site 0851); 🇷🇺 Barnaul, Altayskiy Kray, Russian Federation

National Medical Research Radiology Centre ( Site 0869); 🇷🇺 Obninsk, Kaluzskaja Oblast, Russian Federation

First Moscow State Medical University n.a. I.M.Sechenov ( Site 0871); 🇷🇺 Moscow, Moskva, Russian Federation

Volga District Medical Center ( Site 0876); 🇷🇺 Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0852); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Sverdlovsky Regional Clinical hospital #1 ( Site 0868); 🇷🇺 Ekaterinburg, Sverdlovskaya Oblast, Russian Federation

Wits Clinical Research ( Site 0603); 🇿🇦 Johannesburg, Gauteng, South Africa

Sverdlovsk Regional Oncology Hospital ( Site 0867); 🇷🇺 Ekaterinburg, Sverdlovskaya Oblast, Russian Federation

Steve Biko Academic Hospital ( Site 0601); 🇿🇦 Pretoria, Gauteng, South Africa

Hospital Universitario Central de Asturias ( Site 0654); 🇪🇸 Oviedo, Asturias, Spain

Institut Català d'Oncologia (ICO) - Girona ( Site 0653); 🇪🇸 Girona, Gerona, Spain

Groote Schuur Hospital ( Site 0602); 🇿🇦 Cape Town, Western Cape, South Africa

Xarxa Assistencial Universitaria Manresa ( Site 0655); 🇪🇸 Manresa, Barcelona, Spain

CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 0660); 🇪🇸 Santiago de Compostela, La Coruna, Spain

Fundación Instituto Valenciano de Oncología-Oncologico ( Site 0662); 🇪🇸 Valencia, Valenciana, Comunitat, Spain

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0661); 🇪🇸 Barcelona, Spain

Hospital Virgen del Rocio ( Site 0659); 🇪🇸 Sevilla, Spain

Taipei Veterans General Hospital ( Site 1201); 🇨🇳 Taipei, Taiwan

MNPE Regional Center of Oncology ( Site 0955); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

Zhytomyr Regional Oncology Center ( Site 0961); 🇺🇦 Zhytomyr, Zhytomyrska Oblast, Ukraine

Lviv Oncology Regional Treatment and Diagnostic Center ( Site 0960); 🇺🇦 Lviv, Lvivska Oblast, Ukraine

Imperial College Healthcare NHS Foundation Trust - St Mary's Hospital ( Site 1802); 🇬🇧 London, London, City Of, United Kingdom

Korea University Anam Hospital ( Site 1357); 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital ( Site 1351); 🇰🇷 Seoul, Korea, Republic of

Hospital Clinico Universitario San Carlos de Madrid ( Site 0651); 🇪🇸 Madrid, Spain

CancerCare Manitoba ( Site 0108); 🇨🇦 Winnipeg, Manitoba, Canada

UF Health ( Site 0031); 🇺🇸 Gainesville, Florida, United States

University of Louisville, James Graham Brown Cancer Center ( Site 0022); 🇺🇸 Louisville, Kentucky, United States

Wake Forest Baptist Health ( Site 0014); 🇺🇸 Winston-Salem, North Carolina, United States

University of Wisconsin Hospital and Clinics ( Site 0037); 🇺🇸 Madison, Wisconsin, United States

Hospital Universitario Insular de Gran Canaria ( Site 0657); 🇪🇸 Las Palmas de Gran Canaria, Las Palmas, Spain

I.I. Mechnykov Dnipropetrovsk Regional Clinical Hospital ( Site 0959); 🇺🇦 Dnipro, Dnipropetrovska Oblast, Ukraine

Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval ( Site 0952); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine