Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)
- Conditions
- Metastatic Hormone-Sensitive Prostate Cancer
- Interventions
- Registration Number
- NCT04191096
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus Androgen Deprivation Therapy (ADT) versus placebo plus enzalutamide plus ADT in participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) and 2) overall survival (OS). As of 19-JAN-2023, the study was unblinded and all study participants stopped ongoing treatment with pembrolizumab/placebo and will continue to receive Standard of Care treatment until meeting protocol-specified discontinuation criteria if deriving clinical benefit. Safety analysis will be performed at the end of the study; there will be no further analyses for efficacy and electronic patient-reported outcome (ePRO) endpoints collected from participants beyond the IA1 cutoff date. All study participants will stop ongoing treatment with pembrolizumab/placebo. Exceptions may be requested for study participants who, in the assessment of their study physician, are benefitting from the combination of enzalutamide and pembrolizumab, after consulting with the Sponsor. All other study participants should be discontinued from study and be offered standard of care (SOC) treatment as deemed necessary by the Investigator. If enzalutamide as SOC is not accessible off study to the participant, central sourcing may continue. As of Amendment 04, disease progression will no longer be centrally verified, participants will only be assessed locally. As of Amendment 4, Second Course treatment is not an option for participants. There are currently no participants in the Second Course Phase.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 1251
- Male participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
- Has metastatic disease assessed by investigator and verified by BICR by either ≥2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
- Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study treatment or have a history of bilateral orchiectomy
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
- Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
- Has adequate organ function
- 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
- Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
- Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex
-
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 (non-infectious) pneumonitis that required steroids or has current pneumonitis
-
Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
-
Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
-
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 had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
-
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 a history of clinically significant ventricular arrhythmias
-
Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
-
Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for >39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
-
Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
-
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-programmed cell death-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
-
Has received a live vaccine within 30 days prior to randomization
-
Has a "superscan" bone scan
-
Has had an allogenic tissue/solid organ transplant
-
Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
-
Has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer with the following exceptions:
- Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel
- May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization
- For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization
- Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Enzalutamide + ADT Pembrolizumab Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met. Pembrolizumab + Enzalutamide + ADT Enzalutamide Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met. Pembrolizumab + Enzalutamide + ADT Androgen Deprivation Therapy (ADT) Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met. Placebo + Enzalutamide + ADT Enzalutamide Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met. Placebo + Enzalutamide + ADT Androgen Deprivation Therapy (ADT) Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met. Placebo + Enzalutamide + ADT Placebo Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.
- 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 (BICR) Up to approximately 32 months rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.
Overall Survival (OS) Up to approximately 32 months OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
- Secondary Outcome Measures
Name Time Method Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) Up to Approximately 32 months TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.
Time to First Symptomatic Skeletal-related Event (TTSSRE) Up to Approximately 32 months TTSSRE was the time from randomization to the first symptomatic skeletal-related event defined as: use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.
Time to Prostate-specific Antigen (PSA) Progression Up to Approximately 32 months Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was 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. Time to PSA was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date.
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR Up to Approximately 32 months The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable 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 Use Up to Approximately 32 months TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a \>2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) For participants symptomatic at baseline (average BPI-SF Item 3 score \>0 and/or currently taking opioids; a \>2-point change from baseline in the average BPI-SF Item 3 score and the average worst pain score \>4 and no decrease in average opioid use. TTPP was calculated using the Kaplan-Meier method for censored data. Participants who had \> 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.
Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2) Up to Approximately 32 months PFS2 was defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first.
Prostate-specific Antigen (PSA) Response Rate Up to Approximately 32 Months PSA response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by \>50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed \>3 weeks from the original response.
Prostate-specific Antigen (PSA) Undetectable Up to Approximately 32 Months PSA undetectable rate was defined as the percentage of participants with detectable PSA (\> 0.2 ng/mL) at baseline, which becomes undetectable (\< 0.2 ng/mL) during study treatment.
Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR Up to Approximately 32 Months ORR 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 base 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).
Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR Up to Approximately 32 Months 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 a 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.
Number of Participants Who Experience an Adverse Event (AE) Up to Approximately 59 Months An AE was defined as 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. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Participants who experienced an AE will be reported for each arm.
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) Up to Approximately 59 Months An AE was 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported for each arm.
Trial Locations
- Locations (213)
UCLA Hematology/Oncology - Santa Monica ( Site 0241)
🇺🇸Los Angeles, California, United States
Grupo Medico Camino SC ( Site 2613)
🇲🇽Mexico City, Mexico
Klinikum der Universitaet Muenchen - Grosshadern ( Site 1210)
🇩🇪Muenchen, Bayern, Germany
Klinikum Rechts der Isar ( Site 1206)
🇩🇪Munchen, Bayern, Germany
Radboud University Medical Center ( Site 1606)
🇳🇱Nijmegen, Gelderland, Netherlands
Asan Medical Center ( Site 0403)
🇰🇷Seoul, Korea, Republic of
Isala Klinieken, Locatie Sophia ( Site 1604)
🇳🇱Zwolle, Overijssel, Netherlands
Centro Estatal de Cancerologia de Chihuahua ( Site 2608)
🇲🇽Chihuahua, Mexico
St. Antonius Ziekenhuis ( Site 1600)
🇳🇱Utrecht, Netherlands
Meander Medisch Centrum ( Site 1602)
🇳🇱Amersfoort, Utrecht, Netherlands
Hospital Militar Central [Lima, Peru] ( Site 2704)
🇵🇪Lima, Peru
Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1709)
🇵🇱Koszalin, Zachodniopomorskie, Poland
Hospital San Lucas Cardiologica del Sureste ( Site 2606)
🇲🇽Tuxtla Gutierrez, Chiapas, Mexico
Centro Oncologico Internacional. SEDNA ( Site 2609)
🇲🇽Mexico City, Mexico
Hospital Universitario Ramon y Cajal ( Site 1902)
🇪🇸Madrid, Spain
Auckland City Hospital ( Site 0321)
🇳🇿Auckland, New Zealand
Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1720)
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Staedtisches Klinikum Braunschweig gGmbH ( Site 1217)
🇩🇪Braunschweig, Niedersachsen, Germany
Szpital Uniwersytecki w Krakowie ( Site 1707)
🇵🇱Krakow, Malopolskie, Poland
Hospital Josep Trueta ( Site 1900)
🇪🇸Girona, Gerona, Spain
Hacettepe Universitesi Tıp Fakultesi ( Site 2105)
🇹🇷Ankara, Turkey
Hospital 12 de Octubre de Madrid ( Site 1903)
🇪🇸Madrid, Spain
Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 2607)
🇲🇽Guadalajara, Jalisco, Mexico
Toho University Sakura Medical Center ( Site 0732)
🇯🇵Sakura, Chiba, Japan
Russian Scientific Center of Roentgenoradiology ( Site 1800)
🇷🇺Moscow, Moskva, Russian Federation
Boca Raton Clinical Research QTO ( Site 2611)
🇲🇽Queretaro, Mexico
Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 2706)
🇵🇪Lima, Peru
Twoja Przychodnia - Szczeciskie Centrum Medyczne ( Site 1721)
🇵🇱Szczecin, Zachodniopomorskie, Poland
Yamaguchi University Hospital ( Site 0746)
🇯🇵Ube, Yamaguchi, Japan
Hospital Clinico San Carlos ( Site 1906)
🇪🇸Madrid, Spain
Harasanshin Hospital ( Site 0747)
🇯🇵Fukuoka, Japan
Nagano Municipal Hospital ( Site 0731)
🇯🇵Nagano, Japan
SBIH City clinical hospital named after D.D. Pletniov ( Site 1813)
🇷🇺Moscow, Moskva, Russian Federation
Hospital Virgen de la Macarena ( Site 1904)
🇪🇸Sevilla, Spain
Nara Medical University Hospital ( Site 0744)
🇯🇵Kashihara, Nara, Japan
Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 2100)
🇹🇷Istanbul, Turkey
Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 2700)
🇵🇪Arequipa, Ariqipa, Peru
Nasz Lekarz Przychodnie Medyczne ( Site 1718)
🇵🇱Torun, Kujawsko-pomorskie, Poland
Kantonsspital St. Gallen ( Site 2000)
🇨🇭St. Gallen, Sankt Gallen, Switzerland
Aberdeen Royal Infirmary ( Site 1315)
🇬🇧Aberdeen, Aberdeen City, United Kingdom
Instituto Catalan de Oncologia - ICO ( Site 1901)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Omsk Clinical Oncology Dispensary ( Site 1809)
🇷🇺Omsk, Omskaya Oblast, Russian Federation
Kantonsspital Graubuenden ( Site 2003)
🇨🇭Chur, Grisons, Switzerland
National Cheng Kung University Hospital ( Site 0503)
🇨🇳Tainan, Taiwan
Hospital Universitario Lucus Augusti ( Site 1905)
🇪🇸Lugo, Spain
Universitaetsspital Zuerich ( Site 2001)
🇨🇭Zuerich, Zurich, Switzerland
Kaohsiung Chang Gung Memorial Hospital ( Site 0504)
🇨🇳Kaohsiung, Taiwan
Chulalongkorn Hospital, Medical Oncology Unit ( Site 0600)
🇹🇭Bangkok, Krung Thep Maha Nakhon, Thailand
Velindre Cancer Centre Hospital ( Site 1322)
🇬🇧Cardiff, United Kingdom
Royal Marsden NHS Foundation Trust ( Site 1318)
🇬🇧London, London, City Of, United Kingdom
National Taiwan University Hospital ( Site 0500)
🇨🇳Taipei, Taiwan
The University of Chicago ( Site 0264)
🇺🇸Chicago, Illinois, United States
Antoni van Leeuwenhoek Ziekenhuis ( Site 1603)
🇳🇱Amsterdam, Noord-Holland, Netherlands
Vrije Universiteit Medisch Centrum ( Site 1601)
🇳🇱Amsterdam, Noord-Holland, Netherlands
Franciscus Gasthuis en Vlietland ( Site 1605)
🇳🇱Schiedam, Zuid-Holland, Netherlands
Comprehensive Cancer Centers of Nevada ( Site 0269)
🇺🇸Las Vegas, Nevada, United States
Tri-State Urologic Services PSC, Inc. ( Site 0253)
🇺🇸Cincinnati, Ohio, United States
Peking University First Hospital ( Site 0800)
🇨🇳Beijing, Beijing, China
Hospital Sao Vicente de Paulo ( Site 2303)
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Cotton-O'Neil Cancer Center ( Site 0228)
🇺🇸Topeka, Kansas, United States
Fiona Stanley Hospital ( Site 0311)
🇦🇺Murdoch, Western Australia, Australia
Centre D Oncologie de Gentilly ( Site 1107)
🇫🇷Nancy, Meurthe-et-Moselle, France
Hospital de Clinicas de Porto Alegre ( Site 2304)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Clinica Universidad Catolica del Maule ( Site 2407)
🇨🇱Talca, Maule, Chile
Herlev og Gentofte Hospital. ( Site 1004)
🇩🇰Herlev, Hovedstaden, Denmark
Odense Universitetshospital ( Site 1003)
🇩🇰Odense, Syddanmark, Denmark
Acibadem Adana Hastanesi ( Site 2106)
🇹🇷Adana, Turkey
Ankara Universitesi Tip Fakultesi. ( Site 2101)
🇹🇷Ankara, Turkey
Ankara Sehir Hastanesi ( Site 2103)
🇹🇷Ankara, Turkey
Konya Necmettin Erbakan University Medical Faculty ( Site 2104)
🇹🇷Konya, Turkey
Osaka City University Hospital ( Site 0741)
🇯🇵Osaka, Japan
University of Colorado, Anschutz Cancer Pavilion ( Site 0236)
🇺🇸Aurora, Colorado, United States
Alaska Clinical Research Center ( Site 0274)
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center ( Site 0276)
🇺🇸Anchorage, Alaska, United States
Hartford HealthCare Medical Group ( Site 0212)
🇺🇸Manchester, Connecticut, United States
City of Hope Medical Center ( Site 0217)
🇺🇸Duarte, California, United States
Winship Cancer Institute of Emory University ( Site 0209)
🇺🇸Atlanta, Georgia, United States
Sibley Memorial Hospital ( Site 0275)
🇺🇸Washington, District of Columbia, United States
The Sidney Kimmel Comprehensive Cancer Center ( Site 0204)
🇺🇸Baltimore, Maryland, United States
Springfield Clinic [Springfield, IL] ( Site 0240)
🇺🇸Springfield, Illinois, United States
Associated Medical Professionals of NY ( Site 0251)
🇺🇸Syracuse, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0270)
🇺🇸New York, New York, United States
Weill Cornell Medical College ( Site 0263)
🇺🇸New York, New York, United States
Duke University ( Site 0206)
🇺🇸Durham, North Carolina, United States
Urology Associates [Nashville, TN] ( Site 0233)
🇺🇸Nashville, Tennessee, United States
Carolina Urologic Research Center ( Site 0259)
🇺🇸Myrtle Beach, South Carolina, United States
Inova Health System ( Site 0205)
🇺🇸Fairfax, Virginia, United States
Seattle Cancer Care Alliance ( Site 0258)
🇺🇸Seattle, Washington, United States
Riverina Cancer Care Center ( Site 0302)
🇦🇺Wagga Wagga, New South Wales, Australia
Port Macquarie Base Hospital ( Site 0301)
🇦🇺Port Macquarie, New South Wales, Australia
Medizinische Universitaet Wien ( Site 0903)
🇦🇹Wien, Austria
Oncocentro Ceara ( Site 2309)
🇧🇷Fortaleza, Ceara, Brazil
Ordensklinikum Linz GmbH Elisabethinen ( Site 0901)
🇦🇹Linz, Oberosterreich, Austria
Krankenhaus der Barmherzigen Brüder Wien ( Site 0904)
🇦🇹Wien, Austria
Instituto de Cancer e Transplante de Curitiba ICTR ( Site 2306)
🇧🇷Curitiba, Parana, Brazil
Clinica de Oncologia Reichow ( Site 2308)
🇧🇷Blumenau, Santa Catarina, Brazil
Fundacao Dr Amaral Carvalho ( Site 2302)
🇧🇷Jau, Sao Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2305)
🇧🇷Sao Paulo, Brazil
CISSS de la Monteregie-Centre ( Site 0105)
🇨🇦Greenfield Park, Quebec, Canada
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0109)
🇨🇦Montreal, Quebec, Canada
CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0106)
🇨🇦Montreal, Quebec, Canada
IC La Serena Research ( Site 2406)
🇨🇱La Serena, Coquimbo, Chile
Centro Investigación del Cáncer James Lind ( Site 2401)
🇨🇱Temuco, Araucania, Chile
CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0101)
🇨🇦Quebec, Canada
Oncocentro ( Site 2400)
🇨🇱Vina del Mar, Valparaiso, Chile
Zhejiang Provincial People's Hospital ( Site 0809)
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University ( Site 0834)
🇨🇳Wenzhou, Zhejiang, China
Institucion Prestadora de Servicios de Salud Clinica de la Costa LTDA ( Site 2504)
🇨🇴Barranquilla, Atlantico, Colombia
Instituto Nacional de Cancerologia E.S.E ( Site 2506)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2509)
🇨🇴Valledupar, Cesar, Colombia
Hemato Oncologos ( Site 2503)
🇨🇴Cali, Valle Del Cauca, Colombia
Rigshospitalet ( Site 1005)
🇩🇰Copenhagen, Hovedstaden, Denmark
Vejle Sygehus ( Site 1002)
🇩🇰Vejle, Syddanmark, Denmark
Aalborg Universitetshospital ( Site 1000)
🇩🇰Aalborg, Nordjylland, Denmark
Keski-Suomen keskussairaala ( Site 1017)
🇫🇮Jyvaskyla, Mellersta Finland, Finland
Tampereen yliopistollinen sairaala ( Site 1022)
🇫🇮Tampere, Pirkanmaa, Finland
HYKS ( Site 1020)
🇫🇮Helsinki, Varsinais-Suomi, Finland
TYKS T-sairaala Syopatautien pkl ( Site 1019)
🇫🇮Turku, Varsinais-Suomi, Finland
Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1114)
🇫🇷Strasbourg, Bas-Rhin, France
Centre Leon-Berard ( Site 1110)
🇫🇷Lyon, Auvergne, France
CHU-Jean Minjoz ( Site 1101)
🇫🇷Besancon, Doubs, France
Centre Georges Francois Leclerc ( Site 1112)
🇫🇷Dijon, Cote-d Or, France
Institut Bergonie ( Site 1104)
🇫🇷Bordeaux, Gironde, France
C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 1117)
🇫🇷Rennes, Ille-et-Vilaine, France
Institut Jean Godinot-Clinical Research Unit ( Site 1118)
🇫🇷Reims, Marne, France
Centre Bourgogne ( Site 1119)
🇫🇷Lille, Nord-Pas-de-Calais, France
St Vincents University Hospital ( Site 1300)
🇮🇪Dublin, Ireland
Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 1102)
🇫🇷Pierre Benite, Rhone, France
Hopital Henri Mondor ( Site 1116)
🇫🇷Creteil, Val-de-Marne, France
Klinikum Nuernberg Nord ( Site 1213)
🇩🇪Nurnberg, Bayern, Germany
Universitaetsklinikum der Technischen Universitaet Dresden ( Site 1204)
🇩🇪Dresden, Sachsen, Germany
Charite Universitaetsmedizin Berlin ( Site 1201)
🇩🇪Berlin, Germany
Universitaetsklinikum Hamburg-Eppendorf ( Site 1212)
🇩🇪Hamburg, Germany
Cork University Hospital ( Site 1304)
🇮🇪Cork, Ireland
Beaumont Hospital ( Site 1302)
🇮🇪Dublin, Ireland
University Hospital Limerick ( Site 1305)
🇮🇪Limerick, Ireland
Tallaght University Hospital ( Site 1301)
🇮🇪Dublin, Ireland
Rambam Medical Center ( Site 1400)
🇮🇱Haifa, Israel
University Hospital Waterford ( Site 1303)
🇮🇪Waterford, Ireland
Hadassah Ein Kerem Medical Center ( Site 1404)
🇮🇱Jerusalem, Israel
Sourasky Medical Center ( Site 1403)
🇮🇱Tel Aviv, Israel
Rabin Medical Center ( Site 1402)
🇮🇱Petach Tikva, Israel
Assaf Harofeh Medical Center ( Site 1405)
🇮🇱Zerifin, Israel
Istituto Clinico Humanitas Research Hospital ( Site 1500)
🇮🇹Rozzano, Lombardia, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 1503)
🇮🇹Meldola, Emilia-Romagna, Italy
Azienda Ospedaliera Cannizzaro ( Site 1501)
🇮🇹Catania, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1508)
🇮🇹Napoli, Italy
Centro Di Riferimento Oncologico ( Site 1511)
🇮🇹Aviano, Pordenone, Italy
IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1509)
🇮🇹Bari, Italy
Istituto Nazionale dei Tumori ( Site 1510)
🇮🇹Milano, Italy
Fondazione Policlinico Universitario A. Gemelli ( Site 1512)
🇮🇹Roma, Italy
Azienda Ospedaliera Santa Maria ( Site 1502)
🇮🇹Terni, Italy
A.O. Verona-Ospedale Civile Maggiore Borgo-Trento ( Site 1504)
🇮🇹Verona, Italy
Ehime University Hospital ( Site 0745)
🇯🇵Toon, Ehime, Japan
Kitasato University Hospital ( Site 0734)
🇯🇵Sagamihara, Kanagawa, Japan
Yokohama City University Medical Center ( Site 0735)
🇯🇵Yokohama, Kanagawa, Japan
Kindai University Hospital ( Site 0743)
🇯🇵Osakasayama, Osaka, Japan
Osaka University Hospital ( Site 0742)
🇯🇵Suita, Osaka, Japan
Saitama Medical University International Medical Center ( Site 0737)
🇯🇵Hidaka, Saitama, Japan
Dokkyo Medical University Saitama Medical Center ( Site 0736)
🇯🇵Koshigaya, Saitama, Japan
Toranomon Hospital ( Site 0740)
🇯🇵Tokyo, Japan
National Cancer Center ( Site 0400)
🇰🇷Gyeonggi-do, Kyonggi-do, Korea, Republic of
Chonnam National University Hwasun Hospital ( Site 0406)
🇰🇷Jeollanam-do, Jeonranamdo, Korea, Republic of
Nippon Medical School Hospital ( Site 0738)
🇯🇵Tokyo, Japan
Tokyo Women's Medical University Hospital ( Site 0739)
🇯🇵Tokyo, Japan
Seoul National University Bundang Hospital ( Site 0401)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Seoul National University Hospital ( Site 0405)
🇰🇷Seoul, Korea, Republic of
Volga District Medical Center Federal Medical and Biological Agency ( Site 1805)
🇷🇺Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1810)
🇷🇺Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation
CHUV (centre hospitalier universitaire vaudois) ( Site 2002)
🇨🇭Lausanne, Vaud, Switzerland
Ramathibodi Hospital. ( Site 0601)
🇹🇭Bangkok, Krung Thep Maha Nakhon, Thailand
Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 2102)
🇹🇷Izmir, Turkey
University College London Hospitals NHS Foundation Trust ( Site 1320)
🇬🇧London, London, City Of, United Kingdom
MidLantic Urology ( Site 0273)
🇺🇸Bala-Cynwyd, Pennsylvania, United States
Gallipoli Medical Research Foundation ( Site 0309)
🇦🇺Greenslopes, Queensland, Australia
Urology of Virginia ( Site 0224)
🇺🇸Virginia Beach, Virginia, United States
Chris OBrien Lifehouse ( Site 0300)
🇦🇺Camperdown, New South Wales, Australia
Peter MacCallum Cancer Centre ( Site 0306)
🇦🇺Melbourne, Victoria, Australia
John Flynn Hospital & Medical Centre ( Site 0308)
🇦🇺Tugun, Queensland, Australia
Box Hill Hospital ( Site 0304)
🇦🇺Box Hill, Victoria, Australia
Monash Health ( Site 0305)
🇦🇺Clayton, Victoria, Australia
CHU de Brest -Site Hopital Morvan ( Site 1103)
🇫🇷Brest, Bretagne, France
The Ottawa Hospital ( Site 0100)
🇨🇦Ottawa, Ontario, Canada
Niagara Health System - St. Catharines ( Site 0107)
🇨🇦St. Catharines, Ontario, Canada
Meir Medical Center ( Site 1401)
🇮🇱Kfar Saba, Israel
Hamamatsu University Hospital ( Site 0748)
🇯🇵Hamamatsu, Shizuoka, Japan
Universitaetsklinikum Freiburg ( Site 1200)
🇩🇪Freiburg, Baden-Wurttemberg, Germany
Universitaetsklinikum Magdeburg A.o.R. ( Site 1211)
🇩🇪Magdeburg, Sachsen-Anhalt, Germany
Kyungpook National University Chilgok Hospital ( Site 0404)
🇰🇷Daegu, Taegu-Kwangyokshi, Korea, Republic of
Sapporo Medical University Hospital ( Site 0730)
🇯🇵Sapporo, Hokkaido, Japan
Chiba Cancer Center ( Site 0733)
🇯🇵Chiba, Japan
Severance Hospital Yonsei University Health System ( Site 0402)
🇰🇷Seoul, Korea, Republic of
Sociedad Medica Aren y Bachero Limitada ( Site 2403)
🇨🇱Santiago, Region M. De Santiago, Chile
Hopital Foch ( Site 1105)
🇫🇷Suresnes, Hauts-de-Seine, France
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1716)
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
St. Vincent Frontier Cancer Center-Research ( Site 0213)
🇺🇸Billings, Montana, United States
Hospital Nacional Guillermo Almenara Irigoyen ( Site 2708)
🇵🇪Lima, Peru
Pontificia Universidad Catolica de Chile ( Site 2402)
🇨🇱Santiago, Region M. De Santiago, Chile
Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1717)
🇵🇱Bytom, Slaskie, Poland
Chang Gung Medical Foundation. Linkou ( Site 0502)
🇨🇳Taoyuan, Taiwan
Taipei Veterans General Hospital ( Site 0501)
🇨🇳Taipei, Taiwan
Administradora Country SA - Clinica del Country ( Site 2507)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Srinagarind Hospital ( Site 0604)
🇹🇭Khon Kaen, Thailand
Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 0900)
🇦🇹Salzburg, Austria
Clinica Alemana ( Site 2408)
🇨🇱Santiago, Region M. De Santiago, Chile
Radomskie Centrum Onkologii ( Site 1701)
🇵🇱Radom, Mazowieckie, Poland
Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna
🇵🇱Poznan, Wielkopolskie, Poland
Faculty of Medicine Siriraj Hospital ( Site 0602)
🇹🇭Bangkok, Krung Thep Maha Nakhon, Thailand
Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1700)
🇵🇱Przemysl, Podkarpackie, Poland
Royal Cornwall Hospitals NHS Trust ( Site 1317)
🇬🇧Truro, Cornwall, United Kingdom
Smilow Cancer Center at Yale-New Haven ( Site 0250)
🇺🇸New Haven, Connecticut, United States
Ralph H. Johnson VA Center ( Site 0256)
🇺🇸Charleston, South Carolina, United States
Clinica Peruano Americana S.A. ( Site 2702)
🇵🇪Trujillo, La Libertad, Peru