Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)
- Conditions
- Prostatic Neoplasms
- Interventions
- Registration Number
- NCT03834506
- 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 docetaxel in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC but have progressed on or are intolerant to Next Generation Hormonal Agent (NHA).
There are two primary study hypotheses.
Hypothesis 1: The combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone with respect to Overall Survival (OS).
Hypothesis 2: The combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone 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
With Amendment 6 (effective date: 29-Sep-2022), all participants will be unblinded and placebo treatment will be stopping. Participants who are deemed to be deriving clinical benefit from treatment may continue at the discretion of the investigator.
The global study for MK-3475-921 enrolled 1030 participants. Of the 1030 total participants enrolled in the global study, 21 were also enrolled in the China extension study for MK-3475-921 (NCT04907227).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 1030
- 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 screening
- 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 received prior treatment with one (but not more than one) NHA (eg, abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC) and either a) progressed through treatment OR b) has become intolerant of the drug
- 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 120 days after the last dose of pembrolizumab or for at least 180 days after the last dose of docetaxel (whichever is longer): Refrain from donating sperm PLUS Use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
- 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 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 (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
- Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
- Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization or who has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to mAbs
- Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g. saw palmetto) prior to randomization
- Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
- 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 co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
- Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
- Has hypersensitivity to docetaxel or polysorbate 80
- Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
- Has received prior targeted small molecule therapy or abiraterone acetate, enzalutamide, apalutamide, or darolutamide within 4 weeks prior to the first dose of study treatment, or has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to a previously administered agent
- Has received prior radiotherapy to within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
- Has received a live vaccine within 30 days prior to randomization
- Has received treatment with 5α reductase inhibitors (eg, finasteride or dutasteride), estrogens, and/or cyproterone within 4 weeks prior to randomization
- Has received prior treatment with ketoconazole for prostate cancer
- 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 120 days after the last dose of study treatment
- Has had an allogenic tissue/solid organ transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo+Docetaxel Placebo Participants receive placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle. Placebo+Docetaxel Dexamethasone Participants receive placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle. Pembrolizumab+Docetaxel Pembrolizumab Participants receive pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle. Pembrolizumab+Docetaxel Docetaxel Participants receive pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle. Pembrolizumab+Docetaxel Prednisone Participants receive pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle. Pembrolizumab+Docetaxel Dexamethasone Participants receive pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle. Placebo+Docetaxel Docetaxel Participants receive placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle. Placebo+Docetaxel Prednisone Participants receive placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle (Q3W) for a maximum of 10 cycles (approximately 7 months). Participants also concomitantly receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each 21-day docetaxel cycle.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to 36.5 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 (K-M) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
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 28 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. Radiological progression as per 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 K-M method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.
- Secondary Outcome Measures
Name Time Method 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 Assessed by the Analgesic Quantification Algorithm (AQA) Score Up to 36.5 months TTPP was the time from randomization to pain progression (PP) based on BPI-SF Item 3 and AQA score. BPI-SF assesses pain intensity; for item 3, participant responses to "Please rate your pain at its worst in the last 24 hours" are scored from 0 (no pain) to 10 (worst pain). A higher score indicates greater pain. AQA captures the intensity of analgesic use in pain management, scored from 0 (no analgesic) to 7 (strong opioid use). A higher score indicates higher intensity of analgesic use.
For participants asymptomatic at baseline, PP was ≥2-point change from baseline in BPI-SF item 3 score OR initiation of opioid use. For participants symptomatic at baseline, PP was ≥2-point change from baseline in the BPI-SF Item 3 score, a score of ≥4 and no decrease in average opioid use OR any increase in opioid use (e.g., 1 point change in AQA score). TTPP was assessed by product-limit K-M method. Participants with \>2 consecutive unevaluable visits were censored at the last evaluable assessment.Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) Up to approximately 27 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 could therefore have been any unfavorable 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 discontinued study treatment due to an AE is presented.
Prostate-specific Antigen (PSA) Response Rate Up to 36.5 months The Prostate-specific Antigen (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. The analysis was performed on participants who had baseline PSA measurements.
Time to Prostate-specific Antigen (PSA) Progression Up to 36.5 months The 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 was PSA decline from baseline; OR
2. ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline
Time to PSA progression was calculated using the product-limit K-M method for censored data. Participants without PSA progression were censored at the last evaluable assessment.Number of Participants Who Experienced an Adverse Event (AE) Up to approximately 30 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 could therefore have been any unfavorable 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 experienced an AE is presented.
Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST) Up to approximately 28 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 K-M method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received.
Duration of Response (DOR) 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 36.5 months DOR was the time from first documented evidence of 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: ≥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) until progressive disease (PD) or death. PD per RECIST 1.1 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 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 K-M method for censored data. If a participant had not progressed, the participant was censored at the date of last disease assessment.
Time to First Symptomatic Skeletal-related Event (SSRE) Up to 36.5 months SSRE was the time from randomization to the first symptomatic skeletal-related event defined as:
1. Use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms
2. Occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral)
3. Occurrence of spinal cord compression
4. Tumor-related orthopedic surgical intervention, whichever occurs first.
The SSRE was calculated using the product-limit K-M method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.Objective Response Rate (ORR) 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 36.5 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 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).
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) as Assessed by Blinded Independent Central Review (BICR) Up to 36.5 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 K-M method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment.
Trial Locations
- Locations (215)
Lakeridge Health ( Site 0117)
🇨🇦Oshawa, Ontario, Canada
Sunnybrook Research Institute ( Site 0108)
🇨🇦Toronto, Ontario, Canada
Mount Sinai Hospital Medical Center ( Site 0042)
🇺🇸Chicago, Illinois, United States
Clinical Research Center of specialized types medical care-Oncology ( Site 0570)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
SPb SBHI City Clinical Oncological Dispensary ( Site 0571)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Duke Cancer Center ( Site 0010)
🇺🇸Durham, North Carolina, United States
Sun Yat Sen Memorial Hospital ( Site 1323)
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Guangzhou Medical University ( Site 1330)
🇨🇳Guangzhou, Guangdong, China
Fudan University Shanghai Cancer Center ( Site 1300)
🇨🇳Shanghai, Shanghai, China
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hollywood Private Hospital ( Site 0163)
🇦🇺Nedlands, Western Australia, Australia
Hospital de Caridade de Ijui ( Site 1038)
🇧🇷Ijui, Rio Grande Do Sul, Brazil
National Hospital Organization Shikoku Cancer Center ( Site 0716)
🇯🇵Matsuyama, Ehime, Japan
Kanazawa University Hospital ( Site 0701)
🇯🇵Kanazawa, Ishikawa, Japan
Kitasato University Hospital ( Site 0705)
🇯🇵Sagamihara, Kanagawa, Japan
Nara Medical University Hospital ( Site 0715)
🇯🇵Kashihara, Nara, Japan
Yamaguchi University Hospital ( Site 0717)
🇯🇵Ube, Yamaguchi, Japan
Nippon Medical School Hospital ( Site 0709)
🇯🇵Tokyo, Japan
Keio University Hospital ( Site 0710)
🇯🇵Tokyo, Japan
Centre Hospitalier Regional du Orleans ( Site 0430)
🇫🇷Orleans, Loiret, France
C.H.U. Lyon Sud ( Site 0436)
🇫🇷Pierre Benite, Rhone, France
Institut Mutualiste Montsouris ( Site 0446)
🇫🇷Paris, France
Centre Leon Berard ( Site 0422)
🇫🇷Lyon, Auvergne, France
Centre D Oncologie de Gentilly ( Site 0432)
🇫🇷Nancy, Meurthe-et-Moselle, France
Hemato Oncologos S.A. ( Site 1065)
🇨🇴Cali, Valle Del Cauca, Colombia
Institut Claudius Regaud IUCT Oncopole ( Site 0418)
🇫🇷Toulouse, Haute-Garonne, France
Centre Jean Perrin ( Site 0434)
🇫🇷Clermont-Ferrand, Auvergne, France
Institut Paoli Calmettes. ( Site 0419)
🇫🇷Marseille, Bouches-du-Rhone, France
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1062)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Hamamatsu University Hospital ( Site 0720)
🇯🇵Hamamatsu, Shizuoka, Japan
Universitaetsklinikum des Saarlandes ( Site 0348)
🇩🇪Homburg, Saarland, Germany
National Cancer Center ( Site 0174)
🇰🇷Goyang-si, Kyonggi-do, Korea, Republic of
Rabin Medical Center ( Site 0545)
🇮🇱Petach-Tikwa, Israel
Uniklinik RWTH Aachen ( Site 0308)
🇩🇪Aachen, Nordrhein-Westfalen, Germany
Soroka Medical Center ( Site 0548)
🇮🇱Beer Sheva, Israel
Universitaetsklinikum Goettingen ( Site 0345)
🇩🇪Goettingen, Niedersachsen, Germany
Cork University Hospital ( Site 0727)
🇮🇪Cork, Ireland
Saitama Medical University International Medical Center ( Site 0708)
🇯🇵Hidaka, Saitama, Japan
Toho University Sakura Medical Center ( Site 0703)
🇯🇵Sakura, Chiba, Japan
University of North Midlands NHS Foundation Trust ( Site 0527)
🇬🇧Stoke-on-Trent, Staffordshire, United Kingdom
Mount Vernon Cancer Centre ( Site 0536)
🇬🇧Northwood, Hertfordshire, United Kingdom
Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)
🇩🇪Freiburg, Baden-Wurttemberg, Germany
University of California San Francisco ( Site 0023)
🇺🇸San Francisco, California, United States
Karmanos Cancer Institute ( Site 0077)
🇺🇸Detroit, Michigan, United States
Nebraska Cancer Specialists ( Site 0034)
🇺🇸Omaha, Nebraska, United States
Oregon Health Sciences University ( Site 0031)
🇺🇸Portland, Oregon, United States
University of South Alabama, Mitchell Cancer Institute ( Site 0065)
🇺🇸Mobile, Alabama, United States
Seoul National University Bundang Hospital ( Site 0175)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Rambam Medical Center ( Site 0543)
🇮🇱Haifa, Israel
Assaf Harofeh MC ( Site 0547)
🇮🇱Beer Yaakov-Zerifin, Israel
Hadassah Ein Kerem Medical Center ( Site 0546)
🇮🇱Jerusalem, Israel
Meir Medical Center ( Site 0544)
🇮🇱Kfar Saba, Israel
Chaim Sheba Medical Center ( Site 0541)
🇮🇱Ramat Gan, Israel
University of Colorado Cancer Center ( Site 0022)
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center ( Site 0080)
🇺🇸Tampa, Florida, United States
Hospital Aleman ( Site 1004)
🇦🇷Buenos Aires, Argentina
CEMAIC ( Site 1014)
🇦🇷Cordoba, Argentina
St. Joseph Heritage Healthcare ( Site 0069)
🇺🇸Fullerton, California, United States
University of Southern California Norris Comprehensive Cancer Center ( Site 0061)
🇺🇸Los Angeles, California, United States
USC Norris Oncology Hematology Newport Beach ( Site 0093)
🇺🇸Newport Beach, California, United States
Georgia Cancer Center at Augusta University ( Site 0026)
🇺🇸Augusta, Georgia, United States
Methodist Hospital- Merriillville ( Site 0008)
🇺🇸Merrillville, Indiana, United States
Henry Ford Health System ( Site 0039)
🇺🇸Detroit, Michigan, United States
Cancer & Hematology Centers of Western Michigan ( Site 0013)
🇺🇸Grand Rapids, Michigan, United States
Washington University School of Medicine ( Site 0057)
🇺🇸Saint Louis, Missouri, United States
St. Vincent Frontier Cancer Center ( Site 0016)
🇺🇸Billings, Montana, United States
Associated Medical Professionals of NY ( Site 0060)
🇺🇸Syracuse, New York, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)
🇺🇸Hackensack, New Jersey, United States
W. G. Bill Hefner VA Medical Center ( Site 0029)
🇺🇸Salisbury, North Carolina, United States
University Hospitals Cleveland Medical Center ( Site 0036)
🇺🇸Cleveland, Ohio, United States
Carolina Urologic Research Center ( Site 0070)
🇺🇸Myrtle Beach, South Carolina, United States
Inova Schar Cancer Institute ( Site 0006)
🇺🇸Fairfax, Virginia, United States
Blue Ridge Cancer Care ( Site 0086)
🇺🇸Roanoke, Virginia, United States
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)
🇦🇷Berazategui, Buenos Aires, Argentina
Virginia Cancer Institute ( Site 0052)
🇺🇸Richmond, Virginia, United States
Instituto de Investigaciones Clinicas ( Site 1000)
🇦🇷Mar del Plata, Buenos Aires, Argentina
Hospital Britanico de Buenos Aires ( Site 1006)
🇦🇷Buenos Aires, Caba, Argentina
Sanatorio Parque ( Site 1002)
🇦🇷Rosario, Santa Fe, Argentina
Instituto Medico Alexander Fleming ( Site 1010)
🇦🇷Buenos Aires, Argentina
Macquarie University ( Site 0151)
🇦🇺Macquarie University, New South Wales, Australia
Port Macquarie Base Hospital ( Site 0153)
🇦🇺Port Macquarie, New South Wales, Australia
John Flynn Hospital & Medical Centre ( Site 0164)
🇦🇺Tugun, Queensland, Australia
Medizinische Universitat Graz ( Site 0374)
🇦🇹Graz, Steiermark, Austria
Redcliffe Hospital ( Site 0161)
🇦🇺Redcliffe, Queensland, Australia
Ordensklinikum Linz GmbH Elisabethinen ( Site 0373)
🇦🇹Linz, Oberosterreich, Austria
SCRI-CCCIT GesmbH ( Site 0371)
🇦🇹Salzburg, Austria
Medizinische Universitaet Wien ( Site 0375)
🇦🇹Wien, Austria
Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 1035)
🇧🇷Itajai, Santa Catarina, Brazil
Hospital de Base de Sao Jose de Rio Preto ( Site 1022)
🇧🇷Sao Jose do Rio Preto, Sao Paulo, Brazil
Nova Scotia Health Authority QEII-HSC ( Site 0114)
🇨🇦Halifax, Nova Scotia, Canada
A.C. Camargo Cancer Center ( Site 1026)
🇧🇷Sao Paulo, Brazil
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
Centro Investigación del Cáncer James Lind ( Site 1041)
🇨🇱Temuco, Araucania, Chile
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0105)
🇨🇦Sherbrooke, Quebec, Canada
CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 0103)
🇨🇦Quebec, Canada
Rey y Oreilly Limitada ( Site 1048)
🇨🇱Temuco, Araucania, Chile
Fundacion Arturo Lopez Perez ( Site 1049)
🇨🇱Santiago, Region M. De Santiago, Chile
Pontificia Universidad Catolica de Chile ( Site 1047)
🇨🇱Santiago, Region M. De Santiago, Chile
Bradford Hill Centro de Investigaciones Clinicas ( Site 1044)
🇨🇱Santiago, Region M. De Santiago, Chile
Centro de Investigaciones Clinicas Vina del Mar ( Site 1042)
🇨🇱Vina del Mar, Valparaiso, Chile
Peking University First Hospital ( Site 1303)
🇨🇳Beijing, Beijing, China
The Fifth Medical Center of PLA General Hospital ( Site 1307)
🇨🇳Beijing, Beijing, China
Beijing Cancer Hospital ( Site 1305)
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Xiamen University ( Site 1319)
🇨🇳Xiamen, Fujian, China
Harbin Medical University Cancer Hospital ( Site 1326)
🇨🇳Harbin, Heilongjiang, China
Hunan Cancer Hospital ( Site 1320)
🇨🇳Changsha, Hunan, China
Henan Cancer Hospital ( Site 1321)
🇨🇳Zhengzhou, Henan, China
Hubei Cancer Hospital ( Site 1329)
🇨🇳Wuhan, Hubei, China
Zhongshan Hospital Fudan University ( Site 1301)
🇨🇳Shanghai, Shanghai, China
The Second Affiliated Hospital of Zhejiang University School of Medicine ( Site 1309)
🇨🇳Hangzhou, Zhejiang, China
Nanjing Drum Tower Hospital ( Site 1312)
🇨🇳Nanjing, Jiangsu, China
Zhejiang Provincial People's Hospital ( Site 1310)
🇨🇳Hangzhou, Zhejiang, China
Hospital Pablo Tobon Uribe ( Site 1066)
🇨🇴Medellin, Antioquia, Colombia
Clinica de la Costa Ltda. ( Site 1073)
🇨🇴Barranquilla, Atlantico, Colombia
Oncomedica S.A. ( Site 1057)
🇨🇴Monteria, Cordoba, Colombia
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1068)
🇨🇴Valledupar, Cesar, Colombia
CHU de Brest -Site Hopital Morvan ( Site 0441)
🇫🇷Brest, Finistere, France
Institut De Cancerologie De L Ouest ( Site 0448)
🇫🇷Saint Herblain, Loire-Atlantique, France
Institut Gustave Roussy ( Site 0416)
🇫🇷Villejuif, Val-de-Marne, France
Studienpraxis Urologie ( Site 0309)
🇩🇪Nuertingen, Baden-Wurttemberg, Germany
Universitaetsklinik fuer Urologie ( Site 0307)
🇩🇪Tuebingen, Baden-Wurttemberg, Germany
Universitaetsklinikum in Mannheim ( Site 0314)
🇩🇪Mannheim, Baden-Wurttemberg, Germany
Universitaetsklinikum Wuerzburg ( Site 0302)
🇩🇪Wuerzburg, Bayern, Germany
Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)
🇩🇪Nuernberg, Bayern, Germany
Klinikum Rechts der Isar ( Site 0300)
🇩🇪Muenchen, Bayern, Germany
Universitaetsklinikum Jena ( Site 0305)
🇩🇪Jena, Thuringen, Germany
Charite Universitaetsmedizin Berlin ( Site 0301)
🇩🇪Berlin, Germany
Mid Western Cancer Centre ( Site 0728)
🇮🇪Limerick, Ireland
Istituto Clinico Humanitas Research Hospital ( Site 0452)
🇮🇹Rozzano, Milano, Italy
Sourasky Medical Center ( Site 0542)
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Cannizzaro ( Site 0458)
🇮🇹Catania, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0457)
🇮🇹Napoli, Italy
Azienda Ospedaliera Santa Maria Terni ( Site 0456)
🇮🇹Terni, Italy
Presidio Ospedaliero Santa Chiara ( Site 0451)
🇮🇹Trento, Italy
National Cancer Center Hospital East ( Site 0702)
🇯🇵Kashiwa, Chiba, Japan
A.O. Universitaria di Modena ( Site 0454)
🇮🇹Modena, Italy
Azienda Ospedaliera San Camillo Forlanini ( Site 0455)
🇮🇹Roma, Italy
Yokohama City University Medical Center ( Site 0706)
🇯🇵Yokohama, Kanagawa, Japan
Kindai University Hospital ( Site 0714)
🇯🇵Osakasayama, Osaka, Japan
Osaka University Hospital ( Site 0713)
🇯🇵Suita, Osaka, Japan
Dokkyo Medical University Saitama Medical Center ( Site 0707)
🇯🇵Koshigaya, Saitama, Japan
Chiba Cancer Center ( Site 0704)
🇯🇵Chiba, Japan
Kyushu University Hospital ( Site 0718)
🇯🇵Fukuoka, Japan
Nagasaki University Hospital ( Site 0719)
🇯🇵Nagasaki, Japan
University of Miyazaki Hospital ( Site 0721)
🇯🇵Miyazaki, Japan
Toranomon Hospital ( Site 0711)
🇯🇵Tokyo, Japan
Seoul National University Hospital ( Site 0171)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 0172)
🇰🇷Seoul, Korea, Republic of
Asan Medical Center ( Site 0176)
🇰🇷Seoul, Korea, Republic of
Medisch Centrum Leeuwarden ( Site 0477)
🇳🇱Leeuwarden, Fryslan, Netherlands
Catharina Ziekenhuis ( Site 0472)
🇳🇱Eindhoven, Noord-Brabant, Netherlands
Ziekenhuisgroep Twente ( Site 0469)
🇳🇱Hengelo, Overijssel, Netherlands
SBIH City clinical hospital named after D.D. Pletniov ( Site 0575)
🇷🇺Moscow, Moskva, Russian Federation
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0565)
🇷🇺Chelyabinsk, Chelyabinskaya Oblast, Russian Federation
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0585)
🇷🇺Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation
Volga District Medical Center Federal Medical and Biological Agency ( Site 0572)
🇷🇺Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation
National Medical Research Radiological Center ( Site 0556)
🇷🇺Moscow, Moskva, Russian Federation
Omsk Clinical Oncology Dispensary ( Site 0568)
🇷🇺Omsk, Omskaya Oblast, Russian Federation
Central Clinical Hospital with Polyclinic ( Site 0562)
🇷🇺Moscow, Moskva, Russian Federation
SBHI Samara Regional Clinical Oncology Dispensary ( Site 0576)
🇷🇺Samara, Samarskaya Oblast, Russian Federation
Leningrad Regional Oncology Center ( Site 0588)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Instituto Catalan de Oncologia - ICO ( Site 0330)
🇪🇸L Hospitalet De Llobregat, Barcelona, Spain
Tomsk National Research Medical Center of Russian Academy of Sciences ( Site 0579)
🇷🇺Tomsk, Tomskaya Oblast, Russian Federation
Hospital Consorci Sanitari Parc Tauli ( Site 0335)
🇪🇸Sabadell, Barcelona, Spain
Hospital Universitario Marques de Valdecilla ( Site 0336)
🇪🇸Santander, Cantabria, Spain
Hospital Clinic ( Site 0323)
🇪🇸Barcelona, Spain
Hospital del Mar ( Site 0333)
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal ( Site 0328)
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria ( Site 0337)
🇪🇸Malaga, Spain
Hospital Clinico San Carlos ( Site 0324)
🇪🇸Madrid, Spain
Hospital Virgen del Rocio ( Site 0329)
🇪🇸Sevilla, Spain
Hospital Universitario HM Sanchinarro ( Site 0322)
🇪🇸Madrid, Spain
China Medical University Hospital ( Site 0132)
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital ( Site 0134)
🇨🇳Tainen, Tainan, Taiwan
Taichung Veterans General Hospital ( Site 0133)
🇨🇳Taichung, Taiwan
Cambridge University Hospitals NHS Trust ( Site 0540)
🇬🇧Cambridge, Cambridgeshire, United Kingdom
University Hospitals Bristol NHS Foundation Trust ( Site 0530)
🇬🇧Bristol, Bristol, City Of, United Kingdom
Taipei Veterans General Hospital ( Site 0135)
🇨🇳Taipei, Taiwan
Barts Cancer Institute ( Site 0483)
🇬🇧London, London, City Of, United Kingdom
Weston Park Hospital ( Site 0539)
🇬🇧Sheffield, England, United Kingdom
Torbay Hospital ( Site 0532)
🇬🇧Torquay, Devon, United Kingdom
Centro de Diagnostico Urologico ( Site 1008)
🇦🇷Buenos Aires, Caba, Argentina
Calvary Mater Newcastle ( Site 0148)
🇦🇺Waratah, New South Wales, Australia
Comprehensive Cancer Centers of Nevada ( Site 0092)
🇺🇸Las Vegas, Nevada, United States
Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)
🇦🇷Buenos Aires, Argentina
St George Hospital ( Site 0157)
🇦🇺Kogarah, New South Wales, Australia
CIUSSS du Bas Saint Laurent - Hopital Regional de Rimouski ( Site 0102)
🇨🇦Rimouski, Quebec, Canada
Hospital Josep Trueta ( Site 0321)
🇪🇸Girona, Gerona, Spain
Instituto Nacional de Cancerologia E.S.E ( Site 1061)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
C.H. de Saint Quentin ( Site 0481)
🇫🇷Saint Quentin, Aisne, France
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
CHU Amiens Picardie Site Sud Amiens ( Site 0438)
🇫🇷Amiens, Somme, France
Tallaght University Hospital ( Site 0730)
🇮🇪Dublin, Ireland
Centro Medico Imbanaco de Cali S.A ( Site 1064)
🇨🇴Cali, Valle Del Cauca, Colombia
Reinier de Graaf Groep ( Site 0484)
🇳🇱Delft, Zuid-Holland, Netherlands
Russian Scientific Center of Radiology ( Site 0559)
🇷🇺Moscow, Moskva, Russian Federation
Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Radboud University Medical Center ( Site 0470)
🇳🇱Nijmegen, Gelderland, Netherlands
VieCuri Medisch Centrum ( Site 0487)
🇳🇱Venlo, Limburg, Netherlands
Ziekenhuis Hilversum ( Site 0466)
🇳🇱Hilversum, Noord-Holland, Netherlands
Hagaziekenhuis ( Site 1201)
🇳🇱Den Haag, Zuid-Holland, Netherlands
Biomelab S A S ( Site 1067)
🇨🇴Barranquilla, Atlantico, Colombia
Jeroen Bosch Ziekenhuis ( Site 1200)
🇳🇱Den Bosch, Noord-Brabant, Netherlands
Antoni van Leeuwenhoek Ziekenhuis ( Site 0480)
🇳🇱Amsterdam, Noord-Holland, Netherlands
National Taiwan University Hospital ( Site 0131)
🇨🇳Taipei, Taiwan
Institut Bergonie ( Site 0421)
🇫🇷Bordeaux, Gironde, France
Institut Sainte Catherine ( Site 0447)
🇫🇷Avignon, Vaucluse, France
Yale Cancer Center ( Site 0038)
🇺🇸New Haven, Connecticut, United States
Oncologos del Occidente S.A. ( Site 1072)
🇨🇴Pereira, Risaralda, Colombia
Ziekenhuis Gelderse Vallei ( Site 0485)
🇳🇱Ede, Gelderland, Netherlands
Royal Marsden Hospital ( Site 0526)
🇬🇧Sutton, England, United Kingdom