Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)
- Conditions
- Prostatic Neoplasms
- Interventions
- Registration Number
- NCT03834493
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to assess the efficacy and safety of the combination of pembrolizumab (MK-3475) and enzalutamide in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC, are abiraterone-naïve, or are intolerant to or progressed on abiraterone acetate. There are two primary study hypotheses.
Hypothesis 1: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to Overall Survival (OS).
Hypothesis 2: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to Radiographic Progression-free Survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 1244
- Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
- Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to randomization
- Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
- Has met one of the following criteria with regard to abiraterone acetate exposure: (1) is abiraterone-naïve; (2) received prior abiraterone acetate for the treatment of mHSPC or mCRPC, for a minimum of 4 weeks and not progressed while on treatment; or (3) received prior abiraterone acetate for the treatment of mHSPC or mCRPC and progressed on treatment after a minimum of 8 weeks treatment (minimum 14 weeks for those with bone progression)
- Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
- Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
- Participants must agree to the following during the study treatment period and for at least 90 days after the last dose of enzalutamide: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom
- Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
- Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
- Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
- Has an active infection (including tuberculosis) requiring systemic therapy
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
- Has known active human immunodeficiency virus (HIV), concurrent active hepatitis B virus (HBV) or known active hepatitis C virus (HCV) infection
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
- Has a history of seizure or any condition that may predispose to seizure
- Has a history of loss of consciousness within 12 months of screening
- Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
- Has bradycardia (heart rate of <50 beats per minute) on the screening electrocardiogram (ECG)
- Has history of prostate cancer progression on ketoconazole
- Has had prior treatment with enzalutamide, apalutamide, darolutamide or cytochrome P450 (CYP) 17 inhibitor other than abiraterone acetate
- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
- Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
- Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization
- Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) prior to randomization
- Has received a live or live attenuated vaccine within 30 days prior to randomization
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
- Has a "superscan" bone scan
- Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of enzalutamide
- Has had an allogenic tissue/solid organ transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Enzalutamide Placebo Participants receive placebo by IV infusion administered on Day 1 Q3W for up to 35 cycles (approximately 2 years) PLUS enzalutamide 160 mg administered PO QD continuously until progression. Pembrolizumab + Enzalutamide Enzalutamide Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) PLUS enzalutamide 160 mg administered orally (PO) once a day (QD) continuously until progression. Placebo + Enzalutamide Enzalutamide Participants receive placebo by IV infusion administered on Day 1 Q3W for up to 35 cycles (approximately 2 years) PLUS enzalutamide 160 mg administered PO QD continuously until progression. Pembrolizumab + Enzalutamide Pembrolizumab Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) PLUS enzalutamide 160 mg administered orally (PO) once a day (QD) continuously until progression.
- Primary Outcome Measures
Name Time Method Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review Up to 40 months (through database cut-off date of 12-Dec-2022) rPFS was defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurred first. The rPFS per PCWG-modified RECIST for all participants is presented.
Overall Survival (OS) Up to 40 months (through database cut-off date of 12-Dec-2022) OS was defined as the time from randomization to death due to any cause. The OS for all participants is presented.
- Secondary Outcome Measures
Name Time Method Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) Up to 40 months (through database cut-off date of 12-Dec-2022) TFST was defined as time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever occurs first. The TFST for all participants is presented.
Time to Prostate-specific Antigen (PSA) Progression Up to 40 months (through database cut-off date of 12-Dec-2022) Time from randomization to PSA progression. PSA progression date is defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.
Prostate-specific Antigen (PSA) Response Rate Up to 40 months (through database cut-off date of 12-Dec-2022) PSA response rate was defined as percentage of participants in the analysis population who have a negative change (decrease) in PSA level of ≥50% measured twice ≥3 weeks apart. The analysis was performed on participants who had baseline PSA measurements.
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review Up to 40 months (through database cut-off date of 12-Dec-2022) Time from randomization to radiographic soft tissue progression per PCWG-modified RECIST 1.1
Time to First Symptomatic Skeletal-related Event (SSRE) Up to 40 months (through database cut-off date of 12-Dec-2022) Time from randomization to the first SSRE. SSRE is defined as radiation to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathological fracture, spinal cord compression, or surgery to bone.
Objective Response (OR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review Up to 40 months (through database cut-off date of 12-Dec-2022) OR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on bone scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable \[NE\], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).
Prostate-specific Antigen (PSA) Undetectable Rate Up to 40 months (through database cut-off date of 12-Dec-2022) PSA undetectable rate was defined as percentage of participants in the analysis population with PSA \<0.2 ng/mL during study treatment. The analysis was performed on participants who had baseline PSA measurements.
Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review Up to 40 months (through database cut-off date of 12-Dec-2022) DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for ≥6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. If a participant had not progressed, the participant was censored at the date of last disease assessment.
Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use (Analgesic Quantification Algorithm [AQA] Score) Up to 40 months (through database cut-off date of 12-Dec-2022) Time from randomization to pain progression. In this study, pain progression was assessed by participant responses to Item 3 of the BPI-SF and participant AQA Scores which are both assessed by participants daily for 7 consecutive days.
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) Up to 40 months (through database cut-off date of 12-Dec-2022) An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants who discontinued study treatment due to an AE is presented.
Number of Participants Who Experience an Adverse Event (AE) Up to 40 months (through database cut-off date of 12-Dec-2022) An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants who experienced an AE is presented.
Trial Locations
- Locations (258)
St. Joseph Heritage Healthcare ( Site 0069)
🇺🇸Fullerton, California, United States
Georgia Cancer Center at Augusta University ( Site 0026)
🇺🇸Augusta, Georgia, United States
Gabrail Cancer Center-Research ( Site 0096)
🇺🇸Canton, Ohio, United States
Inova Schar Cancer Institute ( Site 0006)
🇺🇸Fairfax, Virginia, United States
Sunnybrook Research Institute ( Site 0108)
🇨🇦Toronto, Ontario, Canada
University Hospitals Cleveland Medical Center ( Site 0036)
🇺🇸Cleveland, Ohio, United States
Mount Vernon Cancer Centre ( Site 0536)
🇬🇧Northwood, United Kingdom
Sanatorio Parque ( Site 1002)
🇦🇷Rosario, Santa Fe, Argentina
Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)
🇦🇷Buenos Aires, Argentina
Royal Adelaide Hospital ( Site 0154)
🇦🇺Adelaide, South Australia, Australia
Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0116)
🇨🇦Hamilton, Ontario, Canada
Grand River Hospital ( Site 0120)
🇨🇦Kitchener, Ontario, Canada
Princess Margaret Cancer Centre ( Site 0107)
🇨🇦Toronto, Ontario, Canada
CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0103)
🇨🇦Quebec, Canada
C.H. de Saint Quentin ( Site 0481)
🇫🇷Saint Quentin, Aisne, France
Centre Jean Perrin ( Site 0434)
🇫🇷Clermont-Ferrand, Auvergne, France
Centre D Oncologie de Gentilly ( Site 0432)
🇫🇷Nancy, Meurthe-et-Moselle, France
Mid Western Cancer Centre ( Site 0728)
🇮🇪Limerick, Ireland
Assuta Ashdod Medical Center ( Site 0550)
🇮🇱Ashdod, Israel
Soroka Medical Center ( Site 0549)
🇮🇱Beer Sheva, Israel
Fondazione Policlinico Universitario Agostino Gemelli ( Site 0801)
🇮🇹Roma, Italy
Samsung Medical Center ( Site 0172)
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital ( Site 0171)
🇰🇷Seoul, Korea, Republic of
Asan Medical Center ( Site 0176)
🇰🇷Songpagu, Seoul, Korea, Republic of
Hacettepe Universitesi-oncology hospital ( Site 0615)
🇹🇷Ankara, Turkey
Ankara City Hospital-Medical Oncology ( Site 0616)
🇹🇷Ankara, Turkey
University Hospitals Bristol NHS Foundation Trust ( Site 0530)
🇬🇧Bristol, Bristol, City Of, United Kingdom
Royal Marsden Hospital (Sutton) ( Site 0526)
🇬🇧London, Sutton, United Kingdom
Fiona Stanley Hospital ( Site 0162)
🇦🇺Perth, Western Australia, Australia
Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 1032)
🇧🇷Natal, Rio Grande Do Norte, Brazil
Universitaetsklinikum des Saarlandes ( Site 0348)
🇩🇪Homburg, Saarland, Germany
Universitaetsklinikum Schleswig Holstein. ( Site 0346)
🇩🇪Luebeck, Schleswig-Holstein, Germany
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Quiron Madrid ( Site 0325)
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Tulane Cancer Center ( Site 0066)
🇺🇸New Orleans, Louisiana, United States
Oregon Health Sciences University ( Site 0031)
🇺🇸Portland, Oregon, United States
University of Massachusetts Worcester ( Site 0053)
🇺🇸Worcester, Massachusetts, United States
Comprehensive Cancer Centers of Nevada ( Site 0092)
🇺🇸Las Vegas, Nevada, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)
🇺🇸Hackensack, New Jersey, United States
Instituto Medico Alexander Fleming ( Site 1010)
🇦🇷Buenos Aires, Caba, Argentina
Centro Oncologico de Integracion Regional. COIR ( Site 1007)
🇦🇷Mendoza, Argentina
MHAT Serdika-Second Department of Medical Oncology ( Site 0505)
🇧🇬Sofia, Sofia (stolitsa), Bulgaria
CISSS de la Monteregie-Centre ( Site 0119)
🇨🇦Greenfield Park, Quebec, Canada
Monash Health-Monash Medical Centre ( Site 0147)
🇦🇺Clayton, Victoria, Australia
Carolina Urologic Research Center ( Site 0070)
🇺🇸Myrtle Beach, South Carolina, United States
Munson Medical Center ( Site 0030)
🇺🇸Traverse City, Michigan, United States
Instituto de Investigaciones Clinicas ( Site 1000)
🇦🇷Mar del Plata, Buenos Aires, Argentina
Medizinische Universität Wien ( Site 0375)
🇦🇹Wien, Austria
Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 1040)
🇧🇷São Paulo, Sao Paulo, Brazil
Oncomedica S.A. ( Site 1057)
🇨🇴Monteria, Cordoba, Colombia
Institut De Cancerologie De L Ouest ( Site 0448)
🇫🇷Saint Herblain, Loire-Atlantique, France
Centre Hospitalier Regional du Orleans ( Site 0430)
🇫🇷Orleans, Loiret, France
Centre Hospitalier de Valenciennes ( Site 0439)
🇫🇷Valenciennes, Nord, France
C.H.U. Lyon Sud ( Site 0436)
🇫🇷Pierre Benite, Rhone, France
Klinikum Rechts der Isar ( Site 0300)
🇩🇪Muenchen, Bayern, Germany
Universitaetsklinikum Muenster ( Site 0320)
🇩🇪Muenster, Nordrhein-Westfalen, Germany
Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1321)
🇭🇺Kecskemét, Bacs-Kiskun, Hungary
Toho University Sakura Medical Center ( Site 0703)
🇯🇵Sakura, Chiba, Japan
Gold Coast University Hospital ( Site 0150)
🇦🇺Southport, Queensland, Australia
Centro Medico Dra De Salvo ( Site 1018)
🇦🇷Buenos Aires, Argentina
Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1036)
🇧🇷Curitiba, Parana, Brazil
A.C. Camargo Cancer Center ( Site 1026)
🇧🇷Sao Paulo, Brazil
Complex Cancer Center Plovdiv-First Medical Oncology Department ( Site 0507)
🇧🇬Plovdiv, Bulgaria
Bradfordhill ( Site 1044)
🇨🇱Santiago, Region M. De Santiago, Chile
Institut Claudius Regaud IUCT Oncopole ( Site 0418)
🇫🇷Toulouse, Haute-Garonne, France
Institut Gustave Roussy ( Site 0416)
🇫🇷Villejuif, Val-de-Marne, France
St. Vincent Frontier Cancer Center ( Site 0016)
🇺🇸Billings, Montana, United States
Gallipoli Medical Research Foundation ( Site 0149)
🇦🇺Greenslopes, Queensland, Australia
CIUSSS du Bas Saint Laurent - Hopital Regional de Rimouski ( Site 0102)
🇨🇦Rimouski, Quebec, Canada
Institut Mutualiste Montsouris ( Site 0446)
🇫🇷Paris, France
CHU de Brest -Site Hopital Morvan ( Site 0441)
🇫🇷Brest, Bretagne, France
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)
🇦🇷Berazategui, Buenos Aires, Argentina
Hospital Aleman ( Site 1004)
🇦🇷Buenos Aires, Argentina
Ordensklinikum Linz GmbH Elisabethinen ( Site 0373)
🇦🇹Linz, Oberosterreich, Austria
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)
🇨🇦Montreal, Quebec, Canada
Studienpraxis Urologie ( Site 0309)
🇩🇪Nuertingen, Baden-Wurttemberg, Germany
Centro de Diagnostico Urologico ( Site 1008)
🇦🇷Buenos Aires, Caba, Argentina
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1062)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
CHU Jean Minjoz ( Site 0423)
🇫🇷Besancon, Doubs, France
Hopital Foch ( Site 0428)
🇫🇷Suresnes, Hauts-de-Seine, France
Universitaetsklinik fuer Urologie ( Site 0307)
🇩🇪Tuebingen, Baden-Wurttemberg, Germany
Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 1325)
🇭🇺Budapest, Pest, Hungary
Tallaght University Hospital ( Site 0730)
🇮🇪Dublin, Ireland
Hadassah Ein Kerem Medical Center ( Site 0546)
🇮🇱Jerusalem, Israel
Chiba Cancer Center ( Site 0704)
🇯🇵Chiba, Japan
BC Cancer - Victoria ( Site 0111)
🇨🇦Victoria, British Columbia, Canada
Franciscus Gasthuis en Vlietland ( Site 0489)
🇳🇱Schiedam, Zuid-Holland, Netherlands
Salve Medica SP ( Site 0686)
🇵🇱Lodz, Lodzkie, Poland
Lakeridge Health ( Site 0117)
🇨🇦Oshawa, Ontario, Canada
Centro Medico Imbanaco de Cali S.A ( Site 1064)
🇨🇴Cali, Valle Del Cauca, Colombia
Hemato Oncologos S.A. ( Site 1065)
🇨🇴Cali, Valle Del Cauca, Colombia
Charite Universitaetsmedizin Berlin ( Site 0301)
🇩🇪Berlin, Germany
Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 0465)
🇮🇹Verona, Veneto, Italy
Fundacion Arturo Lopez Perez ( Site 1049)
🇨🇱Santiago, Region M. De Santiago, Chile
Biomelab S A S ( Site 1067)
🇨🇴Barranquilla, Atlantico, Colombia
Medical Oncology Ospedale San Donato ( Site 0461)
🇮🇹Arezzo, Italy
Az. Osp. Univ. Sta Maria della Misericordia di Udine ( Site 0460)
🇮🇹Udine, Italy
National Cancer Center Hospital East ( Site 0702)
🇯🇵Kashiwa, Chiba, Japan
Hakodate Goryoukaku Hospital ( Site 0739)
🇯🇵Hakodate, Hokkaido, Japan
Acıbadem Maslak Hastanesi ( Site 0660)
🇹🇷İstanbul, Turkey
Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)
🇩🇪Nuernberg, Bayern, Germany
Istituto Clinico Humanitas Research Hospital ( Site 0452)
🇮🇹Rozzano, Lombardia, Italy
National Hospital Organization Shikoku Cancer Center ( Site 0716)
🇯🇵Matsuyama, Ehime, Japan
Miyagi Cancer Center ( Site 0747)
🇯🇵Natori, Miyagi, Japan
Nara Medical University Hospital ( Site 0715)
🇯🇵Kashihara, Nara, Japan
Hamamatsu University Hospital ( Site 0720)
🇯🇵Hamamatsu, Shizuoka, Japan
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0636)
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Puerto Rico Medical Research Center LLC ( Site 1122)
🇵🇷San Juan, Puerto Rico
Central Clinical Hospital with Polyclinic ( Site 0562)
🇷🇺Moscow, Moskva, Russian Federation
SBHI Leningrad Regional Oncology Dispensary ( Site 0588)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Baskent University Dr. Turgut Noyan Research and Training Center-ONCCOLOGY ( Site 0618)
🇹🇷Adana, Turkey
Kanazawa University Hospital ( Site 0701)
🇯🇵Kanazawa, Ishikawa, Japan
Kitasato University Hospital ( Site 0705)
🇯🇵Sagamihara, Kanagawa, Japan
Yamaguchi University Hospital ( Site 0717)
🇯🇵Ube, Yamaguchi, Japan
Kindai University Hospital ( Site 0714)
🇯🇵Osakasayama, Osaka, Japan
Seoul National University Bundang Hospital ( Site 0175)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Tergooiziekenhuizen ( Site 0466)
🇳🇱Hilversum, Noord-Holland, Netherlands
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0585)
🇷🇺Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation
Dnepropetrovsk Regional Clinical Oncology Hospital-Clinical oncological dispensary ( Site 1201)
🇺🇦Dnipropetrovsk, Dnipropetrovska Oblast, Ukraine
Ivano-Frankivsk Regional Hospital-Urology department ( Site 1208)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
Ziekenhuisgroep Twente ( Site 0469)
🇳🇱Hengelo, Overijssel, Netherlands
Osaka University Hospital ( Site 0713)
🇯🇵Suita, Osaka, Japan
Saitama Medical University International Medical Center ( Site 0708)
🇯🇵Hidaka, Saitama, Japan
Dokkyo Medical University Saitama Medical Center ( Site 0707)
🇯🇵Koshigaya, Saitama, Japan
University of Miyazaki Hospital ( Site 0721)
🇯🇵Miyazaki, Japan
Nagasaki University Hospital ( Site 0719)
🇯🇵Nagasaki, Japan
Noordwest Ziekenhuisgroep NWZ ( Site 0468)
🇳🇱Alkmaar, Noord-Holland, Netherlands
National Cancer Center ( Site 0174)
🇰🇷Goyang-si, Kyonggi-do, Korea, Republic of
Tauranga Hospital ( Site 0215)
🇳🇿Tauranga, Bay Of Plenty, New Zealand
Clinical Best Solutions ( Site 0622)
🇵🇱Warszawa, Mazowieckie, Poland
Taichung Veterans General Hospital ( Site 0133)
🇨🇳Taichung, Taiwan
Russian Scientific Center of Roentgenoradiology ( Site 0559)
🇷🇺Moscow, Moskva, Russian Federation
Torbay Hospital ( Site 0532)
🇬🇧Torquay, Devon, United Kingdom
Musgrove Park Hospital ( Site 0537)
🇬🇧Taunton, Somerset, United Kingdom
Taipei Veterans General Hospital ( Site 0135)
🇨🇳Taipei, Taiwan
Cherkasy Regional Oncology Dispensary ( Site 1203)
🇺🇦Cherkassy, Cherkaska Oblast, Ukraine
Hospital Parc Tauli ( Site 0335)
🇪🇸Sabadell, Barcelona, Spain
China Medical University Hospital ( Site 0132)
🇨🇳Taichung, Taiwan
LISOD - Israeli Oncological Hospital ""MedX-ray Internationa-Department of Clinical and Scientific (
🇺🇦Kiev, Kyivska Oblast, Ukraine
T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training (
🇹🇷Istanbul, Turkey
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0619)
🇹🇷Istanbul, Turkey
Municipal non-profit enterprise Kyiv City Clinical Oncology -Oncourology department ( Site 1204)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
Cambridge University Hospitals NHS Trust ( Site 0540)
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Moffitt Cancer Center ( Site 0080)
🇺🇸Tampa, Florida, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0034)
🇺🇸Omaha, Nebraska, United States
Froedtert Hospital & the Medical College of Wisconsin ( Site 0045)
🇺🇸Milwaukee, Wisconsin, United States
Ege University Medicine of Faculty ( Site 0661)
🇹🇷Bornova, Izmir, Turkey
University of Colorado Cancer Center ( Site 0022)
🇺🇸Aurora, Colorado, United States
Smilow Cancer Hospital at Yale New Haven ( Site 0038)
🇺🇸New Haven, Connecticut, United States
University of South Alabama, Mitchell Cancer Institute ( Site 0065)
🇺🇸Mobile, Alabama, United States
UCLA Hematology/Oncology - Santa Monica ( Site 0081)
🇺🇸Los Angeles, California, United States
Mount Sinai Hospital Medical Center ( Site 0042)
🇺🇸Chicago, Illinois, United States
Methodist Hospitals. ( Site 0008)
🇺🇸Merrillville, Indiana, United States
Cancer & Hematology Centers of Western Michigan ( Site 0013)
🇺🇸Grand Rapids, Michigan, United States
Associated Medical Professionals of NY ( Site 0060)
🇺🇸Syracuse, New York, United States
Tri-State Urologic Services PSC, Inc. ( Site 0094)
🇺🇸Cincinnati, Ohio, United States
W. G. Bill Hefner VA Medical Center ( Site 0029)
🇺🇸Salisbury, North Carolina, United States
Virginia Cancer Institute ( Site 0052)
🇺🇸Richmond, Virginia, United States
Blue Ridge Cancer Care ( Site 0086)
🇺🇸Roanoke, Virginia, United States
Instituto de Oncologia de Rosario ( Site 1015)
🇦🇷Rosario, Santa Fe, Argentina
Centro Oncologico Riojano Integral ( Site 1005)
🇦🇷La Rioja, Argentina
St. Vincent's Hospital ( Site 0158)
🇦🇺Darlinghurst, New South Wales, Australia
CEMAIC ( Site 1014)
🇦🇷Cordoba, Argentina
St George Hospital ( Site 0157)
🇦🇺Kogarah, New South Wales, Australia
Port Macquarie Base Hospital ( Site 0153)
🇦🇺Port Macquarie, New South Wales, Australia
Macquarie University ( Site 0151)
🇦🇺Macquarie University, New South Wales, Australia
Calvary Mater Newcastle ( Site 0148)
🇦🇺Waratah, New South Wales, Australia
ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 1038)
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Hospital de Base de Sao Jose de Rio Preto ( Site 1022)
🇧🇷Sao Jose do Rio Preto, Sao Paulo, Brazil
Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 1035)
🇧🇷Itajai, Santa Catarina, Brazil
MHAT Central Hospital ( Site 0503)
🇧🇬Plovdiv, Bulgaria
Health Sciences North ( Site 0122)
🇨🇦Sudbury, Ontario, Canada
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0105)
🇨🇦Sherbrooke, Quebec, Canada
Centro Investigación del Cáncer James Lind ( Site 1041)
🇨🇱Temuco, Araucania, Chile
Rey y Oreilly Limitada ( Site 1048)
🇨🇱Temuco, Araucania, Chile
Pontificia Universidad Catolica de Chile ( Site 1047)
🇨🇱Santiago, Region M. De Santiago, Chile
Oncocentro ( Site 1045)
🇨🇱Vina del Mar, Valparaiso, Chile
Hospital Pablo Tobon Uribe ( Site 1066)
🇨🇴Medellin, Antioquia, Colombia
Clinica de la Costa Ltda. ( Site 1073)
🇨🇴Barranquilla, Atlantico, Colombia
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1068)
🇨🇴Valledupar, Cesar, Colombia
Fakultni Nemocnice u sv. Anny v Brne-Onkologicko-chirurgicke oddeleni ( Site 1303)
🇨🇿Brno, Brno-mesto, Czechia
Clinique Sainte Anne ( Site 0431)
🇫🇷Strasbourg, Alsace, France
Nemocnice AGEL Novy Jicin a.s. ( Site 1304)
🇨🇿Nový Jičín, Novy Jicin, Czechia
Fakultni nemocnice Olomouc ( Site 1301)
🇨🇿Olomouc, Czechia
Institut Bergonie ( Site 0421)
🇫🇷Bordeaux, Gironde, France
Institut Regional du Cancer de Montpellier - ICM ( Site 0443)
🇫🇷Montpellier, Herault, France
CHU Amiens Picardie Site Sud Amiens ( Site 0438)
🇫🇷Amiens, Somme, France
Institut Sainte Catherine ( Site 0447)
🇫🇷Avignon, Vaucluse, France
Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)
🇩🇪Freiburg, Baden-Wurttemberg, Germany
Uniklinik RWTH Aachen ( Site 0308)
🇩🇪Aachen, Nordrhein-Westfalen, Germany
Universitaetsklinikum Goettingen ( Site 0345)
🇩🇪Goettingen, Niedersachsen, Germany
Krankenhaus der Barmherzigen Brueder Trier ( Site 0310)
🇩🇪Trier, Rheinland-Pfalz, Germany
Petz Aladár Megyei Oktató Kórház-Onkológiai Osztály ( Site 1324)
🇭🇺Gyor, Gyor-Moson-Sopron, Hungary
Universitaetsklinikum Jena ( Site 0305)
🇩🇪Jena, Thuringen, Germany
Beaumont Hospital ( Site 0726)
🇮🇪Dublin, Ireland
Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 1326)
🇭🇺Budapest, Hungary
HaEmek Medical Center ( Site 0548)
🇮🇱Afula, Israel
Rambam Health Care Campus-Oncology Division ( Site 0543)
🇮🇱Haifa, Israel
Meir Medical Center ( Site 0544)
🇮🇱Kfar Saba, Israel
Rabin Medical Center ( Site 0545)
🇮🇱Petach-Tikwa, Israel
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-Oncologia Medica ( Site 0464)
🇮🇹Meldola, Emilia-Romagna, Italy
Sourasky Medical Center ( Site 0542)
🇮🇱Tel Aviv, Israel
Yitzhak Shamir Medical Center ( Site 0547)
🇮🇱Zerifin, Israel
Chaim Sheba Medical Center ( Site 0541)
🇮🇱Ramat Gan, Israel
Ospedale Policlinico S. Orsola-Malpighi ( Site 0453)
🇮🇹Bologna, Italy
Presidio Ospedaliero S. Maria Delle Grazie-U.O.C. ONCOLOGIA ( Site 0802)
🇮🇹Pozzuoli, Napoli, Italy
Centro Di Riferimento Oncologico ( Site 0800)
🇮🇹Aviano, Pordenone, Italy
A.O. Universitaria di Modena ( Site 0454)
🇮🇹Modena, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0462)
🇮🇹Napoli, Italy
Azienda Ospedaliera Santa Maria Terni ( Site 0456)
🇮🇹Terni, Italy
Azienda Ospedaliera San Camillo Forlanini ( Site 0455)
🇮🇹Roma, Italy
Azienda Ospedaliera Cannizzaro ( Site 0458)
🇮🇹Catania, Italy
Iizuka Hospital ( Site 0744)
🇯🇵Iizuka, Fukuoka, Japan
Yokohama City University Medical Center ( Site 0706)
🇯🇵Yokohama, Kanagawa, Japan
Saitama Medical Center ( Site 0743)
🇯🇵Kawagoe, Saitama, Japan
Kyushu University Hospital ( Site 0718)
🇯🇵Fukuoka, Japan
Hiroshima Prefectural Hospital ( Site 0748)
🇯🇵Hiroshima, Japan
Toranomon Hospital ( Site 0711)
🇯🇵Tokyo, Japan
Nippon Medical School Hospital ( Site 0709)
🇯🇵Tokyo, Japan
Keio University Hospital ( Site 0710)
🇯🇵Tokyo, Japan
Radboud University Medical Center ( Site 0470)
🇳🇱Nijmegen, Gelderland, Netherlands
Maastricht University Medical Centre ( Site 0467)
🇳🇱Maastricht, Limburg, Netherlands
Amphia Hospital Location Molengracht ( Site 0474)
🇳🇱Breda, Noord-Brabant, Netherlands
Catharina Ziekenhuis ( Site 0472)
🇳🇱Eindhoven, Noord-Brabant, Netherlands
Vrije Universiteit Medisch Centrum ( Site 0479)
🇳🇱Amsterdam, Noord-Holland, Netherlands
Spaarne Ziekenhuis ( Site 0473)
🇳🇱Hoofddorp, Noord-Holland, Netherlands
Haaglanden MC - locatie Antoniushove ( Site 0471)
🇳🇱Leidschendam, Zuid-Holland, Netherlands
Canterbury Regional Cancer & Blood Service ( Site 0195)
🇳🇿Christchurch, Canterbury, New Zealand
Auckland City Hospital ( Site 0193)
🇳🇿Auckland, New Zealand
Przychodnia Lekarska Komed ( Site 0628)
🇵🇱Konin, Wielkopolskie, Poland
Provita Prolife Centrum Medyczne ( Site 0630)
🇵🇱Tomaszow Mazowiecki, Lodzkie, Poland
Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0624)
🇵🇱Koszalin, Zachodniopomorskie, Poland
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0565)
🇷🇺Chelyabinsk, Chelyabinskaya Oblast, Russian Federation
Omsk Clinical Oncology Dispensary ( Site 0568)
🇷🇺Omsk, Omskaya Oblast, Russian Federation
Fundacion de Investigacion de Diego ( Site 1121)
🇵🇷San Juan, Puerto Rico
SBHI Samara Regional Clinical Oncology Dispensary ( Site 0576)
🇷🇺Samara, Samarskaya Oblast, Russian Federation
Clinical Research Center of specialized types medical care-Oncology ( Site 0570)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Instituto Catalan de Oncologia - ICO ( Site 0330)
🇪🇸L Hospitalet De Llobregat, Barcelona, Spain
Tomsk National Scientific Medical Center of Russian Academy of Science ( Site 0579)
🇷🇺Tomsk, Tomskaya Oblast, Russian Federation
Hospital Josep Trueta ( Site 0321)
🇪🇸Girona, Gerona, Spain
Hospital del Mar ( Site 0333)
🇪🇸Barcelona, Spain
Hospital Provincial San Pedro Alcantara ( Site 0326)
🇪🇸Caceres, Spain
Instituto Valenciano de Oncologia ( Site 0331)
🇪🇸Valencia, Valenciana, Comunitat, Spain
Hospital Universitario Gregorio Maranon ( Site 0327)
🇪🇸Madrid, Spain
MD Anderson Cancer Center Madrid ( Site 0332)
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria ( Site 0337)
🇪🇸Malaga, Spain
Hospital Virgen del Rocio ( Site 0329)
🇪🇸Sevilla, Spain
National Cheng Kung University Hospital ( Site 0134)
🇨🇳Tainen, Tainan, Taiwan
National Taiwan University Hospital ( Site 0131)
🇨🇳Taipei, Taiwan
Ankara University Hospital Cebeci ( Site 0613)
🇹🇷Ankara, Turkey
University College London Hospitals NHS Foundation Trust ( Site 0482)
🇬🇧London, London, City Of, United Kingdom
Western General Hospital ( Site 0531)
🇬🇧Edinburgh, Worcestershire, United Kingdom
Hospital Clinico San Carlos ( Site 0324)
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro ( Site 0322)
🇪🇸Madrid, Spain
Dnepropetrovsk Regional Clinical Hospital Mechnikov-Department of urology ( Site 1205)
🇺🇦Dnipro, Dnipropetrovska Oblast, Ukraine
Communal Non-Commercial Enterprise ""Prykarpatski Clinical Oncological Center"" of Ivano-Frankivsk R
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
CNPE Regional Center of Oncology-oncourology department ( Site 1202)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine