Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Participants Who Are Cisplatin-ineligible or Decline Cisplatin With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)

Phase 3

Active, not recruiting

• Conditions: Urinary Bladder Cancer, Muscle-invasive
• Interventions: Drug: Enfortumab Vedotin; Drug: Pembrolizumab; Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])

• Registration Number: NCT03924895
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This is a study of perioperative pembrolizumab or enfortumab vedotin in combination with pembrolizumab in participants who are cisplatin-ineligible or decline cisplatin with muscle-invasive bladder cancer (MIBC).

The primary hypothesis is that perioperative pembrolizumab plus radical cystectomy (RC) plus pelvic lymph node dissection (PLND) and perioperative enfortumab vedotin in combination with pembrolizumab plus RC+PLND will achieve superior event-free survival (EFS) compared with RC+PLND alone.

With Amendment 5, outcome measures for programmed cell death ligand 1 (PD-L1) combined positive score (CPS) were removed.

With Amendment 8, the primary outcome measure of pathologic complete response (pCR) rates was changed to a secondary outcome measure.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-22
• Study First Submitted QC: 2019-04-22
• Study First Posted: 2019-04-23
• Study Start: 2019-07-24
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-14
• Primary Completion: 2027-05-31
• Study Completion: 2027-12-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 857

Inclusion Criteria

• Have a histologically confirmed diagnosis of urothelial carcinoma/muscle-invasive bladder cancer [MIBC] (cT2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology to be confirmed by Blinded Independent Central Review (BICR) (central pathology and/or imaging).

• Clinically nonmetastatic bladder cancer determined by imaging

• Eligible for radical cystectomy (RC) + pelvic lymph node dissection (PLND), and agreement to undergo curative intent standard RC + PLND (including prostatectomy if applicable)

• Ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria OR be eligible for treatment with cisplatin but decline treatment with cisplatin-based chemotherapy:

  • Impaired renal function with measured or calculated creatinine clearance (CrCl) 30 to 59 mL/min (calculated by Cockcroft-Gault method, Modification of Diet of Renal Disease [MDRD] equations, or measured by 24-hour urine collection)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 2
  • Common Terminology Criteria for Adverse Events (CTCAE) v.4 Grade ≥2 audiometric hearing loss
  • New York Heart Association (NYHA) Class III heart failure

• Transurethral resection (TUR) of a bladder tumor that is submitted for central pathology assessment and adequate to determine urothelial histology and PD-L1 expression assessment

• ECOG performance status of 0, 1, or 2

• Adequate organ function

• A male participant is eligible to participate if he agrees to use contraception and refrain from donating sperm during the intervention period and for at least 180 days after the last dose of enfortumab vedotin. If the male participants are receiving pembrolizumab only or undergoing surgery only, there are no contraception requirements

• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to use a highly effective contraceptive method or be abstinent from heterosexual intercourse (as their preferred and usual lifestyle) during the intervention period and for at least 120 days after the last dose of pembrolizumab and at least 180 days after the last dose of enfortumab vedotin; whichever comes last. A female participant must agree not to donate eggs during this period as well

• A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention

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Exclusion Criteria

• Known additional nonurothelial malignancy that is progressing or has required active anticancer treatment ≤3 years of study randomization, with certain exceptions
• Has ≥ N2 or metastatic disease (M1) as identified by imaging
• Received any prior systemic treatment, chemoradiation, and/or radiation therapy for for muscle-invasive bladder cancer (MIBC) or non-muscle invasive bladder cancer (NMIBC)
• Received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• Received prior systemic anticancer therapy including investigational agents within 3 years prior to randomization
• Received any prior radiotherapy to the bladder
• Received a partial cystectomy of the bladder to remove any non-muscle-invasive bladder cancer (NMIBC) or MIBC
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Current participation in or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of study intervention
• Ongoing sensory or motor neuropathy Grade 2 or higher
• Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
• Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
• Severe hypersensitivity (≥ Grade 3) to enfortumab vedotin or any excipient contained in the drug formulation of enfortumab vedotin
• Active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator
• Active autoimmune disease that has required systemic therapy in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy and is allowed
• Has uncontrolled diabetes
• History of (noninfectious) pneumonitis that required steroids, or current pneumonitis
• Active infection requiring systemic therapy
• Has had an allogeneic tissue/solid organ transplant

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery	Enfortumab Vedotin	Participants receive 3 preoperative cycles of enfortumab vedotin + pembrolizumab, followed by standard of care surgery, followed by 6 cycles of postoperative enfortumab vedotin + pembrolizumab, followed by 8 cycles of pembrolizumab alone. Each cycle is 21 days.
Arm A: Pembrolizumab + Surgery	Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])	Participants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by 14 cycles of postoperative pembrolizumab. Each cycle is 21 days.
Arm B: Surgery alone	Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])	Participants receive standard of care surgery alone.
Arm A: Pembrolizumab + Surgery	Pembrolizumab	Participants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by 14 cycles of postoperative pembrolizumab. Each cycle is 21 days.

Primary Outcome Measures

Name	Time	Method
Event-Free Survival (EFS) between Arm C and Arm B	Up to approximately 6.75 years	EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery or failure to undergo RC surgery in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy, or death due to any cause.

Secondary Outcome Measures

Name	Time	Method
EFS between Arm A and Arm B	Up to approximately 6.75 years	EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery or failure to undergo RC surgery in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy, or death due to any cause.
Overall Survival (OS) between Arm C and Arm B	Up to approximately 7.6 years	OS is defined as the time from randomization to death due to any cause.
OS between Arm A and Arm B	Up to approximately 7.6 years	OS is defined as the time from randomization to death due to any cause.
Pathologic Complete Response (pCR) Rate between Arm C and Arm B	Up to approximately 5.7 years	Pathologic complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as determined centrally.
pCR Rate between Arm A and Arm B	Up to approximately 5.7 years	Pathologic complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as determined centrally.
Disease-Free Survival (DFS)	Up to approximately 6.75 years	DFS is defined as the time from first post-surgery baseline scan until: * local or distant recurrence as assessed by imaging and/or biopsy; * Death due to any cause
Pathologic Downstaging (pDS) Rate between Arm A and Arm B	Up to approximately 5.7 years	Pathologic downstaging rate is defined as the percentage of participants having pDS. pDS is defined as participants with a tumor classification of \<pT2 (includes pT0, pTis, pTa, pT1) and N0 in examined tissue from RC and PLND.
pDS Rate between Arm C and Arm B	Up to approximately 5.7 years	Pathologic downstaging rate is defined as the percentage of participants having pDS. pDS is defined as participants with a tumor classification of \<pT2 (includes pT0, pTis, pTa, pT1) and N0 in examined tissue from RC and PLND.
Number of Participants Experiencing Adverse Events (AEs)	Up to approximately 7.6 years	An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs)	Up to approximately 1 year	An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
Number of Participants Experiencing Perioperative Complications	Up to approximately 1 year	The number of participants who experience perioperative complications will be presented.

Trial Locations

Locations (242)

Princess Margaret Cancer Centre ( Site 0107); 🇨🇦 Toronto, Ontario, Canada

University of Chicago ( Site 0068); 🇺🇸 Chicago, Illinois, United States

Hospital Universitario San Carlos ( Site 0678); 🇪🇸 Madrid, Spain

Scripps MD Anderson ( Site 0010); 🇺🇸 La Jolla, California, United States

Greater Baltimore Medical Center ( Site 0014); 🇺🇸 Baltimore, Maryland, United States

M Health Fairview Ridges Hospital ( Site 1555); 🇺🇸 Burnsville, Minnesota, United States

Morristown Medical Center ( Site 0015); 🇺🇸 Morristown, New Jersey, United States

UNM Comprehensive Cancer Center-Clinical Research Office ( Site 0045); 🇺🇸 Albuquerque, New Mexico, United States

New York University Perlmutter Cancer Center ( Site 0008); 🇺🇸 New York, New York, United States

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0021); 🇺🇸 Tulsa, Oklahoma, United States

Abramson Cancer Center of the University of Pennsylvania ( Site 0074); 🇺🇸 Philadelphia, Pennsylvania, United States

Thomas Jefferson University ( Site 1579); 🇺🇸 Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center ( Site 0055); 🇺🇸 Philadelphia, Pennsylvania, United States

Allegheny General Hospital ( Site 0048); 🇺🇸 Pittsburgh, Pennsylvania, United States

Inova Schar Cancer Institute ( Site 0007); 🇺🇸 Fairfax, Virginia, United States

Charleston Area Medical Center ( Site 0023); 🇺🇸 Charleston, West Virginia, United States

Macquarie University ( Site 1251); 🇦🇺 Macquarie Park, New South Wales, Australia

Western Sydney Local Health District ( Site 1259); 🇦🇺 Blacktown, New South Wales, Australia

Cairns Base Hospital ( Site 1257); 🇦🇺 Cairns, Queensland, Australia

Mater Misericordiae Ltd ( Site 1258); 🇦🇺 South Brisbane, Queensland, Australia

Monash Health ( Site 1260); 🇦🇺 Clayton, Victoria, Australia

UCL Saint-Luc - Oncologie Medicale ( Site 0357); 🇧🇪 Bruxelles, Bruxelles-Capitale, Region De, Belgium

UZ Leuven ( Site 0361); 🇧🇪 Leuven, Vlaams-Brabant, Belgium

Tom Baker Cancer Centre ( Site 0100); 🇨🇦 Calgary, Alberta, Canada

Dana-Farber Cancer Institute ( Site 1596); 🇺🇸 Boston, Massachusetts, United States

Hopital Bichat du Paris ( Site 0462); 🇫🇷 Paris, France

Vivantes Klinikum am Urban ( Site 0529); 🇩🇪 Berlin, Germany

A.O.U. Policlinico Vittorio Emanuele - Presidio Gaspare Rodolico ( Site 0559); 🇮🇹 Catania, Italy

Azienda Ospedaliera Santa Maria Terni-S.C. Oncologia Medica e Traslazionale ( Site 0564); 🇮🇹 Terni, Italy

Kyungpook National University Chilgok Hospital-Urology ( Site 1357); 🇰🇷 Deagu, Taegu-Kwangyokshi, Korea, Republic of

Centro de Urologia Avanzada del Noreste S.A. de C.V. ( Site 0253); 🇲🇽 Monterrey, Nuevo Leon, Mexico

Leningrad Regional Oncology Center ( Site 0868); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Hospital Clinic i Provincial ( Site 0674); 🇪🇸 Barcelona, Cataluna, Spain

Karadeniz Teknik Universitesi Tip Fakultesi Farabi Hastanesi ( Site 0924); 🇹🇷 Trabzon, Turkey

Indiana University Melvin and Bren Simon Comprehensive Cancer Center ( Site 0004); 🇺🇸 Indianapolis, Indiana, United States

Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council (; 🇺🇦 Antonivka Village, Khersonska Oblast, Ukraine

CHU UCL Namur Site de Godinne ( Site 0354); 🇧🇪 Yvoir, Namur, Belgium

Zhytomyr Regional Oncology Center ( Site 0971); 🇺🇦 Zhytomyr, Zhytomyrska Oblast, Ukraine

Wichita Urology Group ( Site 0059); 🇺🇸 Wichita, Kansas, United States

Urology Associates [Nashville, TN] ( Site 0053); 🇺🇸 Nashville, Tennessee, United States

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0105); 🇨🇦 Montreal, Quebec, Canada

BC Cancer Vancouver-Clinical Trials Unit ( Site 0121); 🇨🇦 Vancouver, British Columbia, Canada

Silverado Resarch Inc. ( Site 0111); 🇨🇦 Victoria, British Columbia, Canada

Vanderbilt University Medical Center ( Site 0017); 🇺🇸 Nashville, Tennessee, United States

AZ Maria Middelares Gent ( Site 0353); 🇧🇪 Gent, Oost-Vlaanderen, Belgium

CIUSSS du Saguenay-Lac-St-Jean ( Site 0116); 🇨🇦 Chicoutimi, Quebec, Canada

Soroka Medical Center ( Site 0849); 🇮🇱 Beer Sheva, Israel

Rabin Medical Center ( Site 0847); 🇮🇱 Petach Tikva, Israel

Tohoku University Hospital ( Site 2301); 🇯🇵 Sendai-shi, Miyagi, Japan

Nagano Municipal Hospital ( Site 2309); 🇯🇵 Tomitake, Nagano, Japan

Centro Estatal de Cancerologia de Chihuahua ( Site 0254); 🇲🇽 Chihuahua, Mexico

Bialostockie Centrum Onkologii ( Site 1072); 🇵🇱 Bialystok, Podlaskie, Poland

Bayandin Murmansk Regional Clinical Hospital ( Site 0859); 🇷🇺 Murmansk, Murmanskaya Oblast, Russian Federation

Volga District Medical Center Federal Medical and Biological Agency ( Site 0857); 🇷🇺 Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation

CARTI Cancer Center ( Site 1577); 🇺🇸 Little Rock, Arkansas, United States

Carolina Urologic Research Center ( Site 0062); 🇺🇸 Myrtle Beach, South Carolina, United States

Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 1001); 🇭🇺 Budapest, Hungary

Bon Secours St. Francis Health System ( Site 1572); 🇺🇸 Greenville, South Carolina, United States

AZ Sint-Jan Brugge ( Site 0352); 🇧🇪 Brugge, West-Vlaanderen, Belgium

AZ Delta vzw-Oncology ( Site 0362); 🇧🇪 Roeselare, West-Vlaanderen, Belgium

Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 1007); 🇭🇺 Kaposvar, Hungary

Rambam Health Care Campus-Oncology Division ( Site 0845); 🇮🇱 Haifa, Israel

St. Marianna University Hospital ( Site 2321); 🇯🇵 Kawasaki, Kanagawa, Japan

Kitasato University Hospital ( Site 2306); 🇯🇵 Sagamihara, Kanagawa, Japan

Nara Medical University Hospital ( Site 2312); 🇯🇵 Kashihara, Nara, Japan

Osaka Rosai Hospital ( Site 2320); 🇯🇵 Sakai, Osaka, Japan

Tokyo Medical and Dental University Hospital ( Site 2303); 🇯🇵 Bunkyō, Tokyo, Japan

Centro de Tratamiento de Cancer ( Site 0266); 🇲🇽 Metepec, Mexico

The Medical City ( Site 1752); 🇵🇭 Pasig City, National Capital Region, Philippines

St. Luke s Medical Center ( Site 1751); 🇵🇭 Quezon City, National Capital Region, Philippines

Luxmed Onkologia sp. z o. o. ( Site 1051); 🇵🇱 Warszawa, Mazowieckie, Poland

Saratov State Medical University n.a. V.I.Razumovskiy ( Site 0866); 🇷🇺 Saratov, Saratovskaya Oblast, Russian Federation

Fundacion Valle del Lili- CIC-Fundacion Valle del Lili ( Site 2005); 🇨🇴 Cali, Valle Del Cauca, Colombia

Moncton Hospital - Horizon Health Network ( Site 0112); 🇨🇦 Moncton, New Brunswick, Canada

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 2002); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0492); 🇫🇷 Rennes, Ille-et-Vilaine, France

Asociación de Beneficencia Hospital Sirio Libanés ( Site 2102); 🇦🇷 Buenos Aires, Caba, Argentina

Oncomédica S.A.S ( Site 2001); 🇨🇴 Montería, Cordoba, Colombia

Centre Francois Baclesse ( Site 0459); 🇫🇷 Caen, Calvados, France

Hadassah Ein Kerem Medical Center ( Site 0841); 🇮🇱 Jerusalem, Israel

Meir Medical Center ( Site 0846); 🇮🇱 Kfar Saba, Israel

Sourasky Medical Center ( Site 0850); 🇮🇱 Tel Aviv, Israel

Dokkyo Medical University Saitama Medical Center ( Site 2304); 🇯🇵 Koshigaya, Saitama, Japan

Hamamatsu University Hospital ( Site 2311); 🇯🇵 Hamamatsu, Shizuoka, Japan

Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V. ( Site 0300); 🇲🇽 Aguascalientes, Mexico

Europejskie Centrum Zdrowia Otwock ( Site 1058); 🇵🇱 Otwock, Mazowieckie, Poland

Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1061); 🇵🇱 Bielsko-Biala, Slaskie, Poland

Clinical Research Center Medic-R ( Site 1073); 🇵🇱 Poznań, Wielkopolskie, Poland

Ivanovo Regional Oncology Dispensary ( Site 0852); 🇷🇺 Ivanovo, Ivanovskaya Oblast, Russian Federation

Medical Sanitary Unit Neftyannik ( Site 0888); 🇷🇺 Tyumen, Tyumenskaya Oblast, Russian Federation

Ramathibodi Hospital. ( Site 1451); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

Lister Hospital ( Site 0739); 🇬🇧 Stevenage, Hertfordshire, United Kingdom

Eastern Health ( Site 1255); 🇦🇺 Box Hill, Victoria, Australia

Toranomon Hospital ( Site 2322); 🇯🇵 Minato-ku, Tokyo, Japan

Sarawak General Hospital ( Site 1701); 🇲🇾 Kuching, Sarawak, Malaysia

MNPE City Clinical Hospital #4 of Dnipro Regional Council ( Site 0951); 🇺🇦 Dnipro, Dnipropetrovska Oblast, Ukraine

Jewish General Hospital ( Site 0120); 🇨🇦 Montreal, Quebec, Canada

Fundación Colombiana de Cancerología Clínica Vida ( Site 2003); 🇨🇴 Medellin, Antioquia, Colombia

Institut de Cancerologie du Gard - CHU Caremeau ( Site 0490); 🇫🇷 Nimes, Gard, France

Institut Gustave Roussy ( Site 0487); 🇫🇷 Villejuif, Val-de-Marne, France

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

University Hospital Waterford ( Site 0747); 🇮🇪 Waterford, Ireland

National Cancer Center Hospital East ( Site 2305); 🇯🇵 Kashiwa, Chiba, Japan

Yokosukakyosai ( Site 2307); 🇯🇵 Yokosuka, Kanagawa, Japan

Toyama University Hospital ( Site 2308); 🇯🇵 Toyoma, Toyama, Japan

Instituto Nacional de Cancerologia. ( Site 0256); 🇲🇽 Ciudad de Mexico, Mexico

Central Clinical Hospital with outpatient Clinic ( Site 0856); 🇷🇺 Moscow, Moskva, Russian Federation

First St. Petersburg State Medical University n.a. acad. I.P. Pavlov ( Site 0872); 🇷🇺 Saint-Petersburg, Sankt-Peterburg, Russian Federation

Tan Tock Seng Hospital ( Site 1804); 🇸🇬 Singapore, Central Singapore, Singapore

SNPE National Cancer Institute ( Site 0962); 🇺🇦 Kyiv, Kyivska Oblast, Ukraine

Fundación Cardiovascular de Colombia ( Site 2004); 🇨🇴 Piedecuesta, Santander, Colombia

Cherkasy Regional Oncology Dispensary ( Site 0959); 🇺🇦 Cherkasy, Cherkaska Oblast, Ukraine

Kursk Regional Clinical Oncology Dispensary ( Site 0854); 🇷🇺 Kursk, Kurskaya Oblast, Russian Federation

CHU Hotel Dieu Nantes ( Site 0458); 🇫🇷 Nantes, Loire-Atlantique, France

Petz Aladar Megyei Oktato Korhaz ( Site 1012); 🇭🇺 Gyor, Hungary

THE MEDICAL CITY ILOILO ( Site 1756); 🇵🇭 Iloilo City, Iloilo, Philippines

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0861); 🇷🇺 Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation

First Moscow State Medical University n.a. I.M.Sechenov ( Site 0884); 🇷🇺 Moscow, Moskva, Russian Federation

Sverdlovsk Regional Oncology Hospital ( Site 0874); 🇷🇺 Ekaterinburg, Sverdlovskaya Oblast, Russian Federation

AULSS8 Berica-Ospedale S.Bortolo-ONCOLOGIA CLINICA ( Site 0562); 🇮🇹 Vicenza, Veneto, Italy

Lviv State Regional Oncological Center ( Site 0967); 🇺🇦 Lviv, Lvivska Oblast, Ukraine

National University Hospital ( Site 1802); 🇸🇬 Singapore, Central Singapore, Singapore

Hosp. Gral. Universitari Germans Trias i Pujol ( Site 0675); 🇪🇸 Badalona, Barcelona, Spain

Municipal Non-profit Enterprise of Kharkiv Regional Council RCSDRPP ( Site 0973); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

Faculty of Medicine Siriraj Hospital ( Site 1452); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

ME І.І. Mechnykov Dnipro Regional Clinical Hospital ( Site 0963); 🇺🇦 Dnipropetrovsk, Dnipropetrovska Oblast, Ukraine

MNPE Lviv Regional Clinical Hospital of Lviv Regional Council ( Site 0955); 🇺🇦 Lviv, Lvivska Oblast, Ukraine

Odense Universitetshospital ( Site 0413); 🇩🇰 Odense, Syddanmark, Denmark

University of South Alabama, Mitchell Cancer Institute ( Site 1582); 🇺🇸 Mobile, Alabama, United States

St. Joseph Heritage Healthcare ( Site 0046); 🇺🇸 Fullerton, California, United States

Emory School of Medicine ( Site 0006); 🇺🇸 Atlanta, Georgia, United States

John Wayne Cancer Institute ( Site 0075); 🇺🇸 Santa Monica, California, United States

Parkview Cancer Institute ( Site 0077); 🇺🇸 Fort Wayne, Indiana, United States

Georgetown University Medical Center ( Site 0022); 🇺🇸 Washington, District of Columbia, United States

John H. Stroger Jr. Hospital of Cook County ( Site 1551); 🇺🇸 Chicago, Illinois, United States

New England Cancer Specialists ( Site 0070); 🇺🇸 Scarborough, Maine, United States

Icahn School of Medicine at Mount Sinai ( Site 0031); 🇺🇸 New York, New York, United States

Cleveland Clinic Main ( Site 1576); 🇺🇸 Cleveland, Ohio, United States

Northwell Health - Monter Cancer Center ( Site 0083); 🇺🇸 Lake Success, New York, United States

MidLantic Urology ( Site 0089); 🇺🇸 Bala-Cynwyd, Pennsylvania, United States

Texas Oncology-Baylor Sammons Cancer Center ( Site 1552); 🇺🇸 Dallas, Texas, United States

Sunnybrook Research Institute ( Site 0110); 🇨🇦 Toronto, Ontario, Canada

CIUSSS de l'Estrie-CHUS ( Site 0106); 🇨🇦 Sherbrooke, Quebec, Canada

McGill University Health Centre ( Site 0123); 🇨🇦 Montréal, Quebec, Canada

Herlev og Gentofte Hospital. ( Site 0412); 🇩🇰 Herlev, Hovedstaden, Denmark

Rigshospitalet University Hospital ( Site 0411); 🇩🇰 Kobenhavn, Hovedstaden, Denmark

Aarhus University Hospital Skejby ( Site 0418); 🇩🇰 Aarhus, Midtjylland, Denmark

Centre Georges Francois Leclerc ( Site 0488); 🇫🇷 Dijon, Cote-d Or, France

Hopital de la Timone ( Site 0489); 🇫🇷 Marseille, Bouches-du-Rhone, France

CHU Jean Minjoz ( Site 0455); 🇫🇷 Besancon, Doubs, France

Hopital Belle Isle ( Site 0452); 🇫🇷 Vantoux, Moselle, France

CHU de Bordeaux- Hopital Saint Andre ( Site 0456); 🇫🇷 Bordeaux, Gironde, France

C.H.U. Lyon Sud ( Site 0466); 🇫🇷 Pierre Benite, Rhone, France

Institut Claudius Regaud IUCT Oncopole ( Site 0486); 🇫🇷 Toulouse, Haute-Garonne, France

CHU de Montpellier - Hopital Saint-Eloi ( Site 0469); 🇫🇷 Montpellier, Languedoc-Roussillon, France

Hopital Europeen Georges Pompidou ( Site 0476); 🇫🇷 Paris, France

CHU Cochin ( Site 0475); 🇫🇷 Paris, France

Klinikum der Universitaet Muenchen - Grosshadern ( Site 0548); 🇩🇪 Muenchen, Bayern, Germany

Klinikum Stuttgart - Katharinenhospital ( Site 0520); 🇩🇪 Stuttgart, Baden-Wurttemberg, Germany

Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0549); 🇩🇪 Tuebingen, Baden-Wurttemberg, Germany

Universitaetsklinikum Wuerzburg ( Site 0547); 🇩🇪 Wuerzburg, Bayern, Germany

Universitaetsklinikum Bonn ( Site 0550); 🇩🇪 Bonn, Nordrhein-Westfalen, Germany

Universitaetsklinikum Magdeburg A.o.R. ( Site 0535); 🇩🇪 Magdeburg, Sachsen-Anhalt, Germany

SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 1010); 🇭🇺 Szeged, Csongrad, Hungary

SRH Wald-Klinikum Gera-Zentrum für klinische Studien ( Site 0533); 🇩🇪 Gera, Thuringen, Germany

Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0528); 🇩🇪 Hamburg, Germany

Tallaght University Hospital ( Site 0734); 🇮🇪 Dublin, Ireland

Ha Emek Medical Center ( Site 0843); 🇮🇱 Afula, Israel

Shaare Zedek Medical Center ( Site 0842); 🇮🇱 Jerusalem, Israel

Sheba Medical Center ( Site 0844); 🇮🇱 Ramat Gan, Israel

Yitzhak Shamir Medical Center. ( Site 0848); 🇮🇱 Zerifin, Israel

Policlinico Gemelli di Roma ( Site 0558); 🇮🇹 Roma, Abruzzo, Italy

Azienda USL 8 di Arezzo-Medical Oncology ( Site 0565); 🇮🇹 Arezzo, Italy

Istituto Nazionale Studio e Cura dei Tumori ( Site 0551); 🇮🇹 Milano, Italy

Ospedale San Raffaele-Oncologia Medica ( Site 0561); 🇮🇹 Milano, Lombardia, Italy

Fondazione Salvatore Maugeri IRCCS ( Site 0554); 🇮🇹 Pavia, Italy

Azienda Sanitaria Ospedaliera S Luigi Gonzaga-SCDU Oncologia Medica ( Site 0563); 🇮🇹 Orbassano, Piemonte, Italy

Istituto Nazionale Per Lo Studio E La Cura Dei Tumori ( Site 0552); 🇮🇹 Napoli, Italy

Tsukuba University Hospital ( Site 2302); 🇯🇵 Tsukuba, Ibaraki, Japan

Saitama Prefectural Cancer Center ( Site 2319); 🇯🇵 Ina-machi, Saitama, Japan

Gifu University Hospital ( Site 2310); 🇯🇵 Gifu, Japan

Kagoshima University Hospital ( Site 2317); 🇯🇵 Kagoshima, Japan

National Cancer Center ( Site 1354); 🇰🇷 Goyang-si, Kyonggi-do, Korea, Republic of

Nagasaki University Hospital ( Site 2315); 🇯🇵 Nagasaki, Japan

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

Seoul National University Bundang Hospital ( Site 1356); 🇰🇷 Seongnam-si, Kyonggi-do, Korea, Republic of

Seoul National University Hospital ( Site 1352); 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center ( Site 1355); 🇰🇷 Songpagu, Seoul, Korea, Republic of

Samsung Medical Center ( Site 1353); 🇰🇷 Seoul, Korea, Republic of

University Malaya Medical Centre ( Site 1702); 🇲🇾 Lembah Pantai, Kuala Lumpur, Malaysia

Hospital Pulau Pinang ( Site 1703); 🇲🇾 Georgetown, Pulau Pinang, Malaysia

Hospital Angeles Roma ( Site 0262); 🇲🇽 Mexico City, Mexico

Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 1068); 🇵🇱 Bydgoszcz, Kujawsko-pomorskie, Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 1063); 🇵🇱 Wroclaw, Dolnoslaskie, Poland

Szpital Wojewodzki ( Site 1062); 🇵🇱 Tarnow, Malopolskie, Poland

Clinic of Bashkortostan State Medical University ( Site 0873); 🇷🇺 Ufa, Baskortostan, Respublika, Russian Federation

Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 0878); 🇷🇺 Moscow, Moskva, Russian Federation

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku ( Site 1057); 🇵🇱 Slupsk, Pomorskie, Poland

Omsk Clinical Oncology Dispensary ( Site 0865); 🇷🇺 Omsk, Omskaya Oblast, Russian Federation

National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0860); 🇷🇺 Saint-Petersburg, Sankt-Peterburg, Russian Federation

Clinical Hospital Saint Luka ( Site 0867); 🇷🇺 St. Petersburg, Sankt-Peterburg, Russian Federation

Hospital San Pedro de Alcantara ( Site 0697); 🇪🇸 Caceres, Extremadura, Spain

Steve Biko Academic Hospital-Medical Oncology ( Site 1601); 🇿🇦 Pretoria, Gauteng, South Africa

Hospital Universitario Quiron Madrid ( Site 0694); 🇪🇸 Pozuelo de Alarcon, Madrid, Comunidad De, Spain

Institut Català d'Oncologia (ICO) - Girona ( Site 0700); 🇪🇸 Girona, Gerona, Spain

Hospital del Mar ( Site 0698); 🇪🇸 Barcelona, Spain

Akademiska Sjukhuset ( Site 1211); 🇸🇪 Uppsala, Uppsala Lan, Sweden

Hospital Universitario la Paz ( Site 0690); 🇪🇸 Madrid, Spain

Hospital de Nuestra Senora de Valme ( Site 0693); 🇪🇸 Sevilla, Spain

Instituto Valenciano de Oncologia - IVO ( Site 0679); 🇪🇸 Valencia, Valenciana, Comunitat, Spain

Laenssjukhuset Ryhov ( Site 1215); 🇸🇪 Jonkoping, Jonkopings Lan, Sweden

Karolinska Universitetssjukhuset Solna ( Site 1212); 🇸🇪 Stockholm, Stockholms Lan, Sweden

Onkologiska kliniken ( Site 1217); 🇸🇪 Goteborg, Vastra Gotalands Lan, Sweden

Hospital Universitario Ramon y Cajal ( Site 0691); 🇪🇸 Madrid, Spain

Cancercentrum ( Site 1214); 🇸🇪 Umea, Vasterbottens Lan, Sweden

Srinagarind Hospital ( Site 1454); 🇹🇭 Khon Kaen, Thailand

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0926); 🇹🇷 Istanbul, Turkey

Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0929); 🇹🇷 Konya, Turkey

Hacettepe Universitesi Tıp Fakultesi ( Site 0931); 🇹🇷 Ankara, Turkey

Maharaj Nakorn Chiangmai Hospital ( Site 1453); 🇹🇭 Chiang Mai, Thailand

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0930); 🇹🇷 Istanbul, Turkey

Sakarya Universitesi Tip Fakultesi ( Site 0933); 🇹🇷 Sakarya, Turkey

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0921); 🇹🇷 Istanbul, Turkey

Regional Oncology Center of Kharkiv ( Site 0958); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

MNPE V.I. Shapoval Regional Medical Clinical Urology and Nephrology Center of KharkivRegCouncil ( Si; 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

The Royal Marsden Foundation Trust ( Site 0726); 🇬🇧 London, London, City Of, United Kingdom

Kent and Canterbury Hospital ( Site 0733); 🇬🇧 Canterbury, England, United Kingdom

Imperial College Healthcare NHS Trust ( Site 0745); 🇬🇧 London, London, City Of, United Kingdom

Kyiv City Clinical Oncology Center ( Site 0960); 🇺🇦 Kyiv, Ukraine

The James Cook University Hospital ( Site 0730); 🇬🇧 Middlesbrough, England, United Kingdom

Barts Health NHS Trust - St Bartholomew s Hospital ( Site 0725); 🇬🇧 London, London, City Of, United Kingdom

Western General Hospital ( Site 0749); 🇬🇧 Edinburgh, Midlothian, United Kingdom

Walsall Manor Hospital-Oncology ( Site 0743); 🇬🇧 Walsall, United Kingdom

Clatterbridge Oncology Centre ( Site 0731); 🇬🇧 Wirral, United Kingdom

Royal Cornwall Hospital ( Site 0727); 🇬🇧 Truro, United Kingdom

Universitaetsklinikum Erlangen ( Site 0546); 🇩🇪 Erlangen, Bayern, Germany

Hoag Memorial Hospital Presbyterian ( Site 1595); 🇺🇸 Newport Beach, California, United States

Universitaetsklinikum Carl Gustav Carus ( Site 0532); 🇩🇪 Dresden, Sachsen, Germany

University of Colorado Hospital ( Site 0098); 🇺🇸 Aurora, Colorado, United States

Providence Portland Medical Center [Portland, OR] ( Site 0095); 🇺🇸 Portland, Oregon, United States

Groote Schuur Hospital ( Site 1602); 🇿🇦 Cape Town, Western Cape, South Africa

Tulane University School of Medicine ( Site 0088); 🇺🇸 New Orleans, Louisiana, United States