Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010)
- Conditions
- Prostatic Neoplasms
- Interventions
- Registration Number
- NCT03834519
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to assess the efficacy and safety of the combination of the polyadenosine 5'-diphosphoribose poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and pembrolizumab in the treatment of participants with mCRPC who have failed to respond to either abiraterone acetate or enzalutamide (but not both) and to chemotherapy.
The primary study hypotheses are that the combination of pembrolizumab plus olaparib is superior to abiraterone acetate or enzalutamide with respect to:
1. Overall Survival (OS) and
2. Radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 as assessed by blinded independent central review (BICR)
As of Amendment 06, the Data Monitoring Committee (DMC) is no longer applicable. Participants still on treatment may have the option to continue receiving study intervention or SOC if they are deriving clinical benefit, until criteria for discontinuation are met. Participants who are still on study treatment and deriving clinical benefit will no longer have tumor response assessments by BICR. However, local tumor imaging assessments should continue per standard of care (SOC) schedule. In addition, electronic patient-reported outcome (ePRO) assessments will no longer be performed and biomarker samples will no longer be collected.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 793
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Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
-
Has prostate cancer progression while receiving androgen deprivation therapy (or post bilateral orchiectomy) within 6 months before screening
-
Has current evidence of metastatic disease documented by bone lesions on bone scan and/or soft tissue disease shown by computed tomography/magnetic resonance imaging (CT/MRI)
-
Has received prior treatment with abiraterone acetate OR enzalutamide, but not both
- Have disease that progressed during or after treatment with abiraterone acetate for either metastatic hormone-sensitive prostate cancer (mHSPC) or mCRP or enzalutamide for mCRPC for at least 8 weeks (at least 14 weeks for participants with bone progression)
- Participants that received abiraterone acetate for mHSPC may not have received abiraterone acetate or enzalutamide for mCRPC
-
Have received docetaxel chemotherapy regimen for metastatic castration-resistant prostate cancer (mCRPC) and have had progressive disease during or after treatment with docetaxel
-
Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
-
If receiving bone resorptive therapy, including but not limited to bisphosphonates or denosumab, must have been receiving stable doses before randomization
-
Must agree to refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention PLUS be abstinent from heterosexual intercourse OR must agree to use contraception unless confirmed to be azoospermic
-
Contraception use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirement above, the local label requirements are to be followed.
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Has provided tumor tissue from a fresh core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed. Participants with bone-only or bone-predominant disease may provide a bone biopsy sample
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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 the past 2 years
- Has a history of (noninfectious) pneumonitis requiring steroids, or has current pneumonitis
- Has known active human immunodeficiency virus (HIV), hepatitis B virus (e.g., hepatitis B surface antigen reactive) or hepatitis C virus (HCV) infection (e.g., HCV RNA [qualitative] is detected)
- Has known active 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 myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- Has (≥Grade 3) hypersensitivity to pembrolizumab and/or any of its excipients
- Has known hypersensitivity to the components or excipients in olaparib, abiraterone acetate, prednisone or prednisolone, or enzalutamide
- Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
- Has received an anticancer monoclonal antibody (mAb) before randomization
- Has received prior treatment with olaparib or any other PARP inhibitor
- Has received prior treatment with apalutamide or darolutamide
- Has received prior treatment with enzalutamide or apalutamide for metastatic hormone-sensitive prostate cancer
- Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA (e.g., saw palmetto) before the date of randomization
- Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
- Has received prior treatment with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, or CD137)
- Is currently receiving either strong or moderate inhibitors of cytochrome P450 [CYP] (CYP3A4) that cannot be discontinued for the duration of the study
- Has received a previous allogenic bone marrow transplant or double umbilical cord transplantation (dUCBT) or a solid organ transplant
- Has received a live vaccine within 30 days prior to the date of randomization
- Is currently participating in or has participated in a study of an investigational agent, or has used an investigational device, within 4 weeks before the date of randomization
- Has a bone "superscan"
- Is expecting to father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of study intervention
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Olaparib Pembrolizumab Participants will receive olaparib 600 mg as two 150 mg oral tablets twice daily (BID) continuously until progression PLUS on Day 1 of each 21-day cycle, pembrolizumab 200 mg by intravenous (IV) infusion for up to 35 cycles (approximately 2 years). Pembrolizumab + Olaparib Olaparib Participants will receive olaparib 600 mg as two 150 mg oral tablets twice daily (BID) continuously until progression PLUS on Day 1 of each 21-day cycle, pembrolizumab 200 mg by intravenous (IV) infusion for up to 35 cycles (approximately 2 years). Next-generation Hormonal Agent Monotherapy (NHA) Abiraterone acetate Participants will receive a single NHA, which will be either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression. Next-generation Hormonal Agent Monotherapy (NHA) Prednisone Participants will receive a single NHA, which will be either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression. Next-generation Hormonal Agent Monotherapy (NHA) Enzalutamide Participants will receive a single NHA, which will be either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression. Next-generation Hormonal Agent Monotherapy (NHA) Prednisolone Participants will receive a single NHA, which will be either abiraterone acetate (participants previously treated with enzalutamide) 1000 mg as two 500 mg or four 250 mg oral tablets once daily (QD) PLUS prednisone or prednisolone 10 mg as one 5 mg tablet BID until progression OR enzalutamide (participants previously treated with abiraterone acetate) 160 mg as four 40 mg oral tablets or capsules OR two 80 mg tablets QD until progression.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to ~31 months Overall survival (OS) is defined as the time from randomization to death due to any cause. The nonparametric Kaplan-Meier method was used to estimate the survival curves.
Radiographic Progression-Free Survival (rPFS) Up to ~26 months rPFS is defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on BICR or death due to any cause, whichever occurred first. Per PCWG-modified RECIST 1.1, PD is 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 or ≥2 new bone lesions was also considered PD. PCWG-modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (\>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1 and PCWG rules include new bone lesions. The rPFS per PCWG-modified RECIST as assessed by BICR for all participants is presented. The nonparametric Kaplan-Meier method was used to estimate the survival curves.
- Secondary Outcome Measures
Name Time Method Time to Initiation of the First Subsequent Anticancer Therapy (TFST) Up to ~26 months TFST is the time from randomization to initiation of the first subsequent anticancer therapy defined as the first anti-cancer treatment not part of the study arm for a given participant, or death, whichever occurs first. The nonparametric Kaplan-Meier method was used to estimate the survival curves.
Objective Response Rate (ORR) Up to ~31 months ORR is 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) bone scan) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1 and Non-PD, non-evaluable (NE), or NED bone scan or CR with non-PD or NE bone scan.) The percentage of participants who experienced CR or PR as assessed by BICR is presented.
Duration of Response (DOR) Up to ~26 months DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per PCWG-modified RECIST 1.1, PD is 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. The appearance of ≥ 2 new bone lesions is also considered PD. DOR as assessed by BICR is presented.
Time to Prostate-Specific Antigen (PSA) Progression Up to ~31 months Time to PSA progression is defined as the 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. The nonparametric Kaplan-Meier method was used to estimate the survival curves.Time to First Symptomatic Skeletal-Related Event (SSRE) Up to ~31 months SSRE is defined as the time from randomization to the first symptomatic skeletal-related event, defined as whichever occurs first:
* First 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 interventionTime to Radiographic Soft Tissue Progression Up to ~31 months Time to radiographic soft tissue progression is defined as the time from randomization to radiographic soft tissue progression per soft tissue rule of PCWG-modified RECIST 1.1. Progression is 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. The appearance of one or more new lesions is also considered progression. Time to radiographic soft tissue progression as assessed by BICR is presented.
Time to Pain Progression (TTPP) Up to ~31 months TTPP is defined as the time from randomization to pain progression as determined by Item 3 of the Brief Pain Inventory Short Form (BPI-SF) and by the Analgesic Quantification Algorithm (AQA) score.
Pain progression is defined as:
1. For participants who are asymptomatic at baseline, a ≥2-point change from baseline in the average (4-7 days) BPI-SF item 3 score at 2 consecutive visits OR initiation of opioid use for pain
2. For participants who are 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 an average worst pain score ≥4 and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of 2 or higher) OR any increase in opioid use at 2 consecutive follow-up visits.
Participants who had more than 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.Number of Participants Who Experience an Adverse Event (AE) Up to ~55 months An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an adverse event are presented.
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) Up to ~1461 Days An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE are presented.
Trial Locations
- Locations (193)
UCLA Hematology/Oncology - Santa Monica ( Site 0081)
🇺🇸Los Angeles, California, United States
Princess Margaret Cancer Centre ( Site 0107)
🇨🇦Toronto, Ontario, Canada
Beth Israel Deaconess Medical Ctr. ( Site 0093)
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute ( Site 0033)
🇺🇸Boston, Massachusetts, United States
The Urology Group- Cincinnati ( Site 0094)
🇺🇸Cincinnati, Ohio, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0005)
🇺🇸Baltimore, Maryland, United States
Chesapeake Urology Research Associates ( Site 0076)
🇺🇸Towson, Maryland, United States
Antoni van Leeuwenhoek Ziekenhuis ( Site 0480)
🇳🇱Amsterdam, Noord-Holland, Netherlands
Vrije Universiteit Medisch Centrum ( Site 0479)
🇳🇱Amsterdam, Noord-Holland, Netherlands
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
C.H. de Saint Quentin ( Site 0481)
🇫🇷Saint Quentin, Aisne, France
National Cheng Kung University Hospital ( Site 0134)
🇨🇳Tainen, Tainan, Taiwan
Medizinische Universitat Graz ( Site 0374)
🇦🇹Graz, Steiermark, Austria
Centre Hospitalier Regional du Orleans ( Site 0430)
🇫🇷Orleans, Loiret, France
CHU Amiens Picardie Site Sud Amiens ( Site 0438)
🇫🇷Amiens, Somme, France
Institut Gustave Roussy ( Site 0416)
🇫🇷Villejuif, Val-de-Marne, France
Cambridge University Hospitals NHS Trust ( Site 0540)
🇬🇧Cambridge, Cambridgeshire, United Kingdom
University of North Midlands NHS Foundation Trust ( Site 0527)
🇬🇧Stoke-on-Trent, Staffordshire, United Kingdom
CHU de Brest -Site Hopital Morvan ( Site 0441)
🇫🇷Brest, Bretagne, France
Radboud University Medical Center ( Site 0470)
🇳🇱Nijmegen, Gelderland, Netherlands
National Taiwan University Hospital ( Site 0131)
🇨🇳Taipei, Taiwan
Musgrove Park Hospital ( Site 0537)
🇬🇧Taunton, England, United Kingdom
Institut Bergonie ( Site 0421)
🇫🇷Bordeaux, Gironde, France
Institut Sainte Catherine ( Site 0447)
🇫🇷Avignon, Vaucluse, France
Sibley Memorial Hospital ( Site 0096)
🇺🇸Washington, District of Columbia, United States
Georgia Cancer Center at Augusta University ( Site 0026)
🇺🇸Augusta, Georgia, United States
Tulane Cancer Center ( Site 0066)
🇺🇸New Orleans, Louisiana, United States
St. Vincent Frontier Cancer Center ( Site 0016)
🇺🇸Billings, Montana, United States
St. Joseph Heritage Healthcare ( Site 0069)
🇺🇸Fullerton, California, United States
Virginia Cancer Institute ( Site 0052)
🇺🇸Richmond, Virginia, United States
Instituto Medico Alexander Fleming ( Site 1010)
🇦🇷Buenos Aires, Argentina
Quincy Medical Group ( Site 0021)
🇺🇸Quincy, Illinois, United States
Gabrail Cancer Center-Research ( Site 0097)
🇺🇸Canton, Ohio, United States
University Hospitals of Cleveland Seidman Cancer Center ( Site 0036)
🇺🇸Cleveland, Ohio, United States
University of New Mexico Cancer Center ( Site 0048)
🇺🇸Albuquerque, New Mexico, United States
Memorial Medical Center ( Site 0095)
🇺🇸Las Cruces, New Mexico, United States
Hospital Britanico de Buenos Aires ( Site 1006)
🇦🇷Buenos Aires, Caba, Argentina
Blue Ridge Cancer Care ( Site 0086)
🇺🇸Roanoke, Virginia, United States
Sanatorio Parque ( Site 1002)
🇦🇷Rosario, Santa Fe, Argentina
Medizinische Universitaet Wien ( Site 0375)
🇦🇹Wien, Austria
Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 1035)
🇧🇷Itajai, Santa Catarina, Brazil
Associated Medical Professionals of NY ( Site 0060)
🇺🇸Syracuse, New York, United States
Duke Cancer Center Cary ( Site 0010)
🇺🇸Cary, North Carolina, United States
Carolina Urologic Research Center ( Site 0070)
🇺🇸Myrtle Beach, South Carolina, United States
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)
🇦🇷Berazategui, Buenos Aires, Argentina
Box Hill Hospital ( Site 0146)
🇦🇺Box Hill, Victoria, Australia
Bradford Hill Centro de Investigaciones Clinicas ( Site 1044)
🇨🇱Santiago, Region M. De Santiago, Chile
Clinique Sainte Anne ( Site 0431)
🇫🇷Strasbourg, Alsace, France
CHU Jean Minjoz ( Site 0423)
🇫🇷Besancon, Doubs, France
Hopital Foch ( Site 0428)
🇫🇷Suresnes, Hauts-de-Seine, France
Royal Brisbane and Women s Hospital ( Site 0155)
🇦🇺Herston, Queensland, Australia
Ordensklinikum Linz GmbH Elisabethinen ( Site 0373)
🇦🇹Linz, Oberosterreich, Austria
SCRI-CCCIT GesmbH ( Site 0371)
🇦🇹Salzburg, Austria
Fiona Stanley Hospital ( Site 0162)
🇦🇺Murdoch, Western Australia, Australia
John Flynn Hospital & Medical Centre ( Site 0164)
🇦🇺Tugun, Queensland, Australia
Hospital de Caridade de Ijui ( Site 1038)
🇧🇷Ijui, Rio Grande Do Sul, Brazil
BC Cancer-Vancouver Center ( Site 0112)
🇨🇦Vancouver, British Columbia, Canada
William Osler Health System (Brampton Civic Hospital) ( Site 0121)
🇨🇦Brampton, Ontario, Canada
Centro Investigación del Cáncer James Lind ( Site 1041)
🇨🇱Temuco, Araucania, Chile
Pontificia Universidad Catolica de Chile ( Site 1047)
🇨🇱Santiago, Region M. De Santiago, Chile
CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0103)
🇨🇦Quebec, Canada
BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0113)
🇨🇦Kelowna, British Columbia, Canada
Rey y Oreilly Limitada ( Site 1048)
🇨🇱Temuco, Araucania, Chile
Institut Claudius Regaud IUCT Oncopole ( Site 0418)
🇫🇷Toulouse, Haute-Garonne, France
Universitaetsklinikum Duesseldorf ( Site 0306)
🇩🇪Duesseldorf, Nordrhein-Westfalen, Germany
Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0116)
🇨🇦Hamilton, Ontario, Canada
Soroka Medical Center ( Site 0549)
🇮🇱Beer Sheva, Israel
Institut Paoli Calmettes ( Site 0419)
🇫🇷Marseille, Bouches-du-Rhone, France
Institut De Cancerologie De L Ouest ( Site 0448)
🇫🇷Saint Herblain, Loire-Atlantique, France
Klinikum Rechts der Isar ( Site 0300)
🇩🇪Muenchen, Bayern, Germany
C.H.U. Lyon Sud ( Site 0436)
🇫🇷Pierre Benite, Rhone, France
National Hospital Organization Shikoku Cancer Center ( Site 0716)
🇯🇵Matsuyama, Ehime, Japan
Toho University Sakura Medical Center ( Site 0703)
🇯🇵Sakura, Chiba, Japan
Krankenhaus der Barmherzigen Brueder Trier ( Site 0310)
🇩🇪Trier, Rheinland-Pfalz, Germany
Hadassah Ein Kerem Medical Center ( Site 0546)
🇮🇱Jerusalem, Israel
Sourasky Medical Center ( Site 0542)
🇮🇱Tel-Aviv, Israel
Centre D Oncologie de Gentilly ( Site 0432)
🇫🇷Nancy, Meurthe-et-Moselle, France
Meir Medical Center ( Site 0544)
🇮🇱Kfar Saba, Israel
Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)
🇩🇪Nuernberg, Bayern, Germany
Fujita Health University Hospital ( Site 0724)
🇯🇵Toyoake, Aichi, Japan
Studienpraxis Urologie ( Site 0309)
🇩🇪Nuertingen, Baden-Wurttemberg, Germany
Tallaght University Hospital ( Site 0730)
🇮🇪Dublin, Ireland
Azienda Ospedaliera San Camillo Forlanini ( Site 0455)
🇮🇹Roma, Italy
Istituto Clinico Humanitas Research Hospital ( Site 0452)
🇮🇹Rozzano, Lombardia, Italy
Osaka International Cancer Institute ( Site 0722)
🇯🇵Osaka, Japan
Dokkyo Medical University Saitama Medical Center ( Site 0707)
🇯🇵Koshigaya, Saitama, Japan
Universitaetsklinikum Erlangen ( Site 0303)
🇩🇪Erlangen, Bayern, Germany
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0565)
🇷🇺Chelyabinsk, Chelyabinskaya Oblast, Russian Federation
Kobe City Medical Center General Hospital ( Site 0726)
🇯🇵Kobe, Hyogo, Japan
Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Ziekenhuisgroep Twente ( Site 0469)
🇳🇱Hengelo, Overijssel, Netherlands
Assaf Harofe ( Site 0547)
🇮🇱Be'er- Ya'akov, Israel
Rabin Medical Center ( Site 0545)
🇮🇱Petach-Tikwa, Israel
Medical Oncology Ospedale San Donato ( Site 0461)
🇮🇹Arezzo, Italy
Presidio Ospedaliero Santa Chiara ( Site 0451)
🇮🇹Trento, Italy
Ha Emek Medical Center ( Site 0548)
🇮🇱Afula, Israel
Yokohama City University Medical Center ( Site 0706)
🇯🇵Yokohama, Kanagawa, Japan
Nagasaki University Hospital ( Site 0719)
🇯🇵Nagasaki, Japan
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0462)
🇮🇹Meldola, Emilia-Romagna, Italy
National Cancer Center Hospital East ( Site 0702)
🇯🇵Kashiwa, Chiba, Japan
Chaim Sheba Medical Center ( Site 0541)
🇮🇱Ramat Gan, Israel
Kyushu University Hospital ( Site 0718)
🇯🇵Fukuoka, Japan
Nagano Municipal Hospital ( Site 0723)
🇯🇵Nagano, Japan
Asan Medical Center ( Site 0171)
🇰🇷Songpagu, Seoul, Korea, Republic of
Haaglanden MC - locatie Antoniushove ( Site 0471)
🇳🇱Leidschendam, Zuid-Holland, Netherlands
Toranomon Hospital ( Site 0711)
🇯🇵Tokyo, Japan
SBHI Samara Regional Clinical Oncology Dispensary ( Site 0576)
🇷🇺Samara, Samarskaya Oblast, Russian Federation
Keio University Hospital ( Site 0710)
🇯🇵Tokyo, Japan
Clinical Research Center of specialized types medical care-Oncology ( Site 0570)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Central Clinical Hospital with Polyclinic ( Site 0562)
🇷🇺Moscow, Moskva, Russian Federation
Severance Hospital Yonsei University Health System ( Site 0173)
🇰🇷Seoul, Korea, Republic of
Erasmus MC ( Site 0475)
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Auckland City Hospital ( Site 0193)
🇳🇿Auckland, New Zealand
SBHI Leningrad Regional Oncology Dispensary ( Site 0588)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
National Cancer Center ( Site 0176)
🇰🇷Goyang-si, Kyonggi-do, Korea, Republic of
Omsk Clinical Oncology Dispensary ( Site 0568)
🇷🇺Omsk, Omskaya Oblast, Russian Federation
Hospital Universitario Virgen de la Victoria ( Site 0337)
🇪🇸Malaga, Spain
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0585)
🇷🇺Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation
Instituto Catalan de Oncologia - ICO ( Site 0330)
🇪🇸L Hospitalet De Llobregat, Barcelona, Spain
Taichung Veterans General Hospital ( Site 0133)
🇨🇳Taichung, Taiwan
University Hospitals Bristol NHS Foundation Trust ( Site 0530)
🇬🇧Bristol, Bristol, City Of, United Kingdom
Mount Vernon Cancer Centre ( Site 0536)
🇬🇧Northwood, United Kingdom
Taipei Veterans General Hospital ( Site 0135)
🇨🇳Taipei, Taiwan
Royal Marsden Hospital ( Site 0526)
🇬🇧Sutton, England, United Kingdom
Azienda Ospedaliera Cannizzaro ( Site 0458)
🇮🇹Catania, Italy
Fondazione Policlinico Universitario A. Gemelli ( Site 0463)
🇮🇹Roma, Italy
Azienda Ospedaliera Santa Maria Terni ( Site 0456)
🇮🇹Terni, Italy
IBCC - Instituto Brasileiro de Controle do Câncer ( Site 1040)
🇧🇷São Paulo, Sao Paulo, Brazil
CIUSSS du Bas Saint Laurent - Hopital Regional de Rimouski ( Site 0102)
🇨🇦Rimouski, Quebec, Canada
Nova Scotia Health Authority QEII-HSC ( Site 0114)
🇨🇦Halifax, Nova Scotia, Canada
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0105)
🇨🇦Sherbrooke, Quebec, Canada
Kanazawa University Hospital ( Site 0701)
🇯🇵Kanazawa, Ishikawa, Japan
Nara Medical University Hospital ( Site 0715)
🇯🇵Kashihara, Nara, Japan
Osaka University Hospital ( Site 0713)
🇯🇵Suita, Osaka, Japan
Saitama Medical University International Medical Center ( Site 0708)
🇯🇵Hidaka, Saitama, Japan
Fuji City General Hospital ( Site 0725)
🇯🇵Fuji, Shizuoka, Japan
Hamamatsu University Hospital ( Site 0720)
🇯🇵Hamamatsu, Shizuoka, Japan
Yamaguchi University Hospital ( Site 0717)
🇯🇵Ube, Yamaguchi, Japan
Nippon Medical School Hospital ( Site 0709)
🇯🇵Tokyo, Japan
Chiba Cancer Center ( Site 0704)
🇯🇵Chiba, Japan
University of Miyazaki Hospital ( Site 0721)
🇯🇵Miyazaki, Japan
Samsung Medical Center ( Site 0172)
🇰🇷Seoul, Korea, Republic of
Hospital Quiron Madrid ( Site 0325)
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Universitaetsklinikum Jena ( Site 0305)
🇩🇪Jena, Thuringen, Germany
Peter MacCallum Cancer Centre ( Site 0152)
🇦🇺Melbourne, Victoria, Australia
Calvary Mater Newcastle ( Site 0148)
🇦🇺Waratah, New South Wales, Australia
Centro de Diagnostico Urologico ( Site 1008)
🇦🇷Buenos Aires, Caba, Argentina
Instituto de Investigaciones Metabolicas ( Site 1011)
🇦🇷Buenos Aires, Argentina
CEMAIC ( Site 1014)
🇦🇷Cordoba, Argentina
UMass Memorial Medical Center ( Site 0053)
🇺🇸Worcester, Massachusetts, United States
Hospital Aleman ( Site 1004)
🇦🇷Buenos Aires, Argentina
Barbara Ann Karmanos Cancer Institute ( Site 0077)
🇺🇸Detroit, Michigan, United States
Henry Ford Health System ( Site 0039)
🇺🇸Detroit, Michigan, United States
Nebraska Cancer Specialists ( Site 0034)
🇺🇸Omaha, Nebraska, United States
Huntsman Cancer Institute ( Site 0002)
🇺🇸Salt Lake City, Utah, United States
Froedtert and Medical College of Wisconsin ( Site 0045)
🇺🇸Milwaukee, Wisconsin, United States
Comprehensive Cancer Centers of Nevada ( Site 0092)
🇺🇸Las Vegas, Nevada, United States
Seattle Cancer Care Alliance ( Site 0079)
🇺🇸Seattle, Washington, United States
A.C. Camargo Cancer Center ( Site 1026)
🇧🇷Sao Paulo, Brazil
Macquarie University ( Site 0151)
🇦🇺Macquarie University, New South Wales, Australia
Port Macquarie Base Hospital ( Site 0153)
🇦🇺Port Macquarie, New South Wales, Australia
Southern Medical Day Care Centre ( Site 0160)
🇦🇺Wollongong, New South Wales, Australia
St. Vincent's Hospital ( Site 0158)
🇦🇺Darlinghurst, New South Wales, Australia
Hospital de Base de Sao Jose de Rio Preto ( Site 1022)
🇧🇷Sao Jose do Rio Preto, Sao Paulo, Brazil
Cross Cancer Institute ( Site 0110)
🇨🇦Edmonton, Alberta, Canada
Fundacion Arturo Lopez Perez ( Site 1049)
🇨🇱Santiago, Region M. De Santiago, Chile
Centre Jean Perrin ( Site 0434)
🇫🇷Clermont-Ferrand, Auvergne, France
Institut Regional du Cancer de Montpellier - ICM ( Site 0443)
🇫🇷Montpellier, Herault, France
Centre Leon Berard ( Site 0422)
🇫🇷Lyon, Rhone, France
Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)
🇩🇪Freiburg, Baden-Wurttemberg, Germany
Institut Mutualiste Montsouris ( Site 0446)
🇫🇷Paris, France
Universitaetsklinikum in Mannheim ( Site 0314)
🇩🇪Mannheim, Baden-Wurttemberg, Germany
Universitaetsklinik fuer Urologie ( Site 0307)
🇩🇪Tuebingen, Baden-Wurttemberg, Germany
Mid Western Cancer Centre ( Site 0728)
🇮🇪Limerick, Ireland
Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0301)
🇩🇪Berlin, Germany
Policlinico S.Orsola-Malpighi ( Site 0453)
🇮🇹Bologna, Italy
Rambam Medical Center ( Site 0543)
🇮🇱Haifa, Israel
Kindai University Hospital ( Site 0714)
🇯🇵Osakasayama, Osaka, Japan
Kitasato University Hospital ( Site 0705)
🇯🇵Sagamihara, Kanagawa, Japan
Chonnam National University Hwasun Hospital ( Site 0174)
🇰🇷Hwasun Gun, Jeonranamdo, Korea, Republic of
Spaarne Ziekenhuis ( Site 0473)
🇳🇱Hoofddorp, Noord-Holland, Netherlands
Medisch Centrum Leeuwarden ( Site 0477)
🇳🇱Leeuwarden, Fryslan, Netherlands
Franciscus Gasthuis en Vlietland ( Site 0489)
🇳🇱Schiedam, Zuid-Holland, Netherlands
Russian Scientific Center of Roentgenoradiology ( Site 0559)
🇷🇺Moscow, Moskva, Russian Federation
Hospital San Pedro de Alcantara ( Site 0326)
🇪🇸Caceres, Extremadura, Spain
Tomsk National Scientific Medical Center of Russian Academy of Science ( Site 0579)
🇷🇺Tomsk, Tomskaya Oblast, Russian Federation
Hospital Parc Tauli ( Site 0335)
🇪🇸Sabadell, Barcelona, Spain
China Medical University Hospital ( Site 0132)
🇨🇳Taichung, Taiwan
Hospital Josep Trueta ( Site 0321)
🇪🇸Girona, Gerona, Spain
Hospital Clinic ( Site 0323)
🇪🇸Barcelona, Spain
Hospital del Mar ( Site 0333)
🇪🇸Barcelona, Spain
Hospital General Universitari Vall d Hebron ( Site 0334)
🇪🇸Barcelona, Spain
Torbay Hospital ( Site 0532)
🇬🇧Torquay, Devon, United Kingdom