Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)

Phase 3

Active, not recruiting

Conditions: Hormone Sensitive Prostate Cancer
Prostate Cancer
Cancer of the Prostate

Interventions: Drug: Enzalutamide
Drug: Placebo (No longer applicable in Open Label study period)
Drug: Leuprolide Open Label

Registration Number: NCT02319837

Lead Sponsor: Pfizer

Brief Summary: The purpose of this study is to assess enzalutamide plus leuprolide in patients with high-risk nonmetastatic prostate cancer progressing after radical prostatectomy or radiotherapy or both.

The randomized / blinded portion of the study is now completed following primary endpoint analyses. The study remains ongoing in open label format.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Male

Target Recruitment: 1068

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features;
Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent;
PSA doubling time ≤ 9 months;
Screening PSA by the central laboratory ≥ 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer;
Serum testosterone ≥ 150 ng/dL (5.2 nmol/L).

Exclusion Criteria

Prior or present evidence of distant metastatic disease as assessed by radiographic imaging;
Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer ≤ 36 months in duration and ≥ 9 months before randomization, or a single dose or a short course (≤ 6 months) of hormonal therapy given for rising PSA ≥ 9 months before randomization is allowed.;
Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer;
Prior systemic biologic therapy, including immunotherapy, for prostate cancer;
Major surgery within 4 weeks before randomization;
Treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks of randomization;
Known or suspected brain metastasis or active leptomeningeal disease;
History of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enzalutamide plus leuprolide	Enzalutamide	Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with leuprolide administered as as a single intramuscular or subcutaneous injection once every 12 weeks
Enzalutamide plus leuprolide	Leuprolide Open Label	Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with leuprolide administered as as a single intramuscular or subcutaneous injection once every 12 weeks
Enzalutamide monotherapy	Enzalutamide	Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily
Leuprolide plus placebo	Placebo (No longer applicable in Open Label study period)	Enzalutamide placebo (placebo) capsules (identical in appearance to enzalutamide) administered as 4 capsules by mouth once daily in combination with leuprolide administered as a single intramuscular or subcutaneous injection once every 12 weeks. The randomized blinded portion of the study has concluded following primary endpoint analyses. In the Open Label Period the placebo is no longer applicable in this study arm, and patients continue to receive leuprolide alone.

Primary Outcome Measures

Name	Time	Method
Metastasis-free Survival (MFS) Compared Between Enzalutamide Plus Leuprolide and Placebo Plus Leuprolide	From randomization until radiographic progression or death without radiographic progression, whichever occurred first (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups)	MFS was defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death without radiographic progression, whichever occurred first. Radiographic progression for soft tissue disease was defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Radiographic progression for bone disease was defined as the appearance of 1 or more metastatic lesions on bone scan (a bone scan assesses 5 regions of the skeleton, including skull, thorax, spine, pelvis, and extremities). Confirmation with a second imaging modality (plain film, computed tomography \[CT\], or magnetic resonance imaging \[MRI\]) was to be required when bone lesions were found in a single region on the bone scan. Appearance of metastatic lesions in 2 or more of the 5 regions on a bone scan was not to require confirmation with a second imaging modality.

Secondary Outcome Measures

Name	Time	Method
Metastasis-free Survival (MFS) Compared Between Enzalutamide Monotherapy and Placebo Plus Leuprolide	From randomization until radiographic progression or death without radiographic progression, whichever occurred first (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups)	MFS was defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death without radiographic progression, whichever occurred first. Radiographic progression for soft tissue disease was defined by RECIST 1.1. Radiographic progression for bone disease was defined as the appearance of 1 or more metastatic lesions on bone scan (a bone scan assesses 5 regions of the skeleton, including skull, thorax, spine, pelvis, and extremities). Confirmation with a second imaging modality (plain film, CT, or MRI) was to be required when bone lesions were found in a single region on the bone scan. Appearance of metastatic lesions in 2 or more of the 5 regions on a bone scan was not to require confirmation with a second imaging modality.
Percentage of Participants With Undetectable Prostate-specific Antigen (PSA) at 36 Weeks on Study Drug	At Week 36	Undetectable PSA at 36 weeks was serum PSA levels \<0.2 ng/mL at Week 36. Percentage of participants with undetectable PSA at 36 weeks on study drug was calculated as the number of participants with undetectable PSA at Week 36 divided by the number of participants with PSA values at Week 36, and multiplied by 100.
Time to Prostate-specific Antigen (PSA) Progression	From randomization until first PSA progression (up to Month 98)	Time to PSA progression was defined as the time in months from randomization to the date of the first PSA value demonstrating progression, while participants were on study treatment, which was subsequently confirmed at least 3 weeks later. PSA progression date was defined as the date that a ≥25% increase and an absolute increase of ≥2 micrograms per liter (μg/L) (2 nanograms per milliliter \[ng/mL\]) above the nadir (or baseline for participants with no PSA decline by Week 25) that was confirmed by a second consecutive value at least 3 weeks later. For participants who had suspended treatment at Week 37 and later reinitiated treatment, baseline was reset as the last PSA assessment prior to or on the date of reinitiation of treatment.
Time to First Use of New Antineoplastic Therapy	From randomization until first use of new antineoplastic therapy (up to Month 98)	Time to first use of new antineoplastic therapy was defined as the time in months from randomization to first use of new antineoplastic therapy for prostate cancer.
Overall Survival (OS)	From randomization until death due to any cause (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups)	Overall survival was defined as the time in months between randomization and death due to any cause.
Time to Distant Metastasis	From randomization until the earliest objective evidence of distant soft tissue metastases or metastatic bone disease (up to Month 98)	The time to distant metastasis was defined as the time in months from randomization to the earliest objective evidence of distant soft tissue metastases or metastatic bone disease by blinded independent central review (BICR).
Percentage of Participants Who Remained Treatment-free 2 Years After Suspension of Study Treatment at Week 37 Due to Undetectable Prostate-specific Antigen (PSA)	From randomization until 2 years after Week 37 (up to Month 34)	Undetectable PSA at 36 weeks was serum PSA levels \<0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (\<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to ≥2.0 ng/mL for participants with prior prostatectomy or ≥5.0 ng/mL for participants without prostatectomy. Percentage of participants who remained treatment-free 2 years after suspension of study treatment at Week 37 was calculated as the number of participants who remained treatment-free 2 years after suspension of study treatment at Week 37 divided by the number of participants with treatment suspension and multiplied by 100.
Time to Resumption of Any Hormonal Therapy Following Suspension at Week 37 Due to Undetectable Prostate-specific Antigen (PSA)	From treatment suspension at Week 37 until resumption of any hormonal therapy (up to Month 98)	Undetectable PSA at 36 weeks was serum PSA levels \<0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (\<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to ≥2.0 ng/mL for participants with prior prostatectomy or ≥5.0 ng/mL for participants without prostatectomy. The time to resumption of any hormonal therapy following suspension at Week 37 due to undetectable PSA was defined as the time in months between the date of treatment suspension at Week 37 due to undetectable PSA and the date that hormonal therapy was restarted.
Percentage of Participants With Undetectable Prostate-specific Antigen (PSA) 2 Years After Suspension of Treatment at Week 37 Due to Undetectable PSA	From randomization until 2 years after Week 37 (up to Month 34)	Undetectable PSA at 36 weeks was serum PSA levels \<0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (\<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to ≥2.0 ng/mL for participants with prior prostatectomy or ≥5.0 ng/mL for participants without prostatectomy. Percentage of participants with undetectable PSA 2 years after suspension of treatment at Week 37 due to undetectable PSA was calculated as the number of participants with undetectable PSA 2 years after suspension of treatment at Week 37 due to undetectable PSA divided by the number of participants with treatment suspension and multiplied by 100.
Time to Symptomatic Progression	From randomization until the first development of events defined as symptomatic progression (up to Month 98)	Time to symptomatic progression was defined as the time in months from randomization to development of a skeletal-related event, worsening of disease-related symptoms requiring initiation of a new antineoplastic therapy, or development of adverse events (AEs) and clinically significant signs and/or symptoms due to loco-regional tumor progression requiring opiate use, surgical intervention or radiation therapy, whichever occurred first.
Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or Grade 4 Post-baseline in Chemistry Laboratory Test Values - at PCD Cut-off Date of 31 January 2023	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)	Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Chemistry laboratory abnormalities were graded according to CTCAE version 4.03 (Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death). This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from ≤Grade 2 at baseline to Grade 3 and Grade 4 post-baseline for the following parameters: alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, calcium, creatine kinase, glucose, magnesium, phosphate, potassium, sodium.
Time to Castration Resistance	From randomization to the first occurrence of radiographic disease progression, PSA progression or SSE, whichever occurred first with castrate levels of testosterone (up to Month 98)	Time to castration resistance applied only to participants receiving leuprolide treatment and was defined as the time in months from randomization to the first occurrence of radiographic disease progression by BICR, PSA progression or symptomatic skeletal event (SSE) whichever occurred first with castrate levels of testosterone (\<50 ng/dL).
Time to First Symptomatic Skeletal Event (SSE)	From randomization until the first development of events defined as SSE (up to Month 98)	Time to first symptomatic skeletal event was defined as the time in months from randomization to use of radiation therapy (external beam radiation therapy or radionuclides) or surgery to bone for prostate cancer, findings of clinically apparent pathologic bone fracture or of spinal cord compression, or new use of opiate and/or systemic antineoplastic therapy due to bone pain collected in the SSE case report form (CRF), whichever occurred first.
Time From Randomization to Onset of Clinically Relevant Pain Progression, Defined as a 2-point or Greater Increase From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Question 3 Score	From randomization until a 2-point or greater increase from baseline in the BPI-SF question 3 score (up to Month 98)	Time to clinically relevant pain progression was defined as the time from randomization to onset of pain progression, where clinically relevant pain progression was defined as a 2-point or greater increase from baseline in the BPI-SF question 3 score. BPI-SF is a self-administered questionnaire containing 9 main questions related to pain and analgesic medication use, where question 3 (paraphrased) is "On a scale of 0 \[no pain\] to 10 \[pain as bad as you can imagine\], please rate your pain at its worst in the last 24 hours" with higher score indicating worse pain.
Time From Randomization to First Assessment With at Least a 10-point Decline (Deterioration) From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score	From randomization to first assessment with at least a 10-point decrease from baseline in the FACT-P total score (up to Month 98)	Time to first deterioration of the FACT-P total score was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the FACT-P total score. FACT-P total score is based on subscale scores of physical, social/family, emotional, and functional well-being, as well as 12 site-specific items to assess prostate-related symptoms, ranging 0-156, with higher score representing better quality of life.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (All-causality) During On-treatment Period, Modified Treatment Period, and Treatment Reinitiation Period - at PCD Cut-off Date of 31 January 2023	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)	An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day. Modified TEAEs (mTEAEs) were AEs that occurred during the modified treatment period (events occurring or worsening during the treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). Reinitiated TEAEs (rTEAEs) were AEs that occurred with a start date during the dosing period after suspension and reinitiation of study treatment as defined by the reinitiation treatment period.
Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) (All-causality) - at PCD Cut-off Date of 31 January 2023	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)	An AE was any untoward medical occurrence (e.g., sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was defined as the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day. The severity of all TEAEs was evaluated by the investigator based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life-threatening) and grade 5 (death related to AE).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Treatment-related) During On-treatment Period, Modified Treatment Period, and Treatment Reinitiation Period - at PCD Cut-off Date of 31 January 2023	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)	An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from date of first dose of study treatment through at least 30 days after last dose of study treatment or start day of new antineoplastic drug therapy minus 1 day. Treatment-related TEAEs were TEAEs attributed to study drug (enzalutamide, placebo or leuprolide). mTEAEs were AEs that occurred during the modified treatment period (events occurring or worsening during the treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). rTEAEs were AEs that occurred with a start date during the dosing period after suspension and reinitiation of study treatment (reinitiation treatment period).
Number of Participants With SAEs (All-causality) During On-treatment Period, Modified Treatment Period and Treatment Reinitiation Period and SAEs (Treatment-related) During On-treatment period-at PCD Cut-off 31 Jan 2023	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)	An AE was any untoward medical occurrence in a participant administered study drug/other protocol-imposed intervention regardless of attribution. SAEs were AEs resulting in any of the following outcomes/deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent/significant disability/incapacity; congenital anomaly. On-treatment period was time from first dose date of study treatment through ≥30 days after last dose of study treatment or start day of new antineoplastic drug therapy -1 day. mSAEs were SAEs occurring during modified treatment period (events occurring/worsening during treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). rSAEs were SAEs occurring with a start date during the dosing period after suspension and reinitiation of study treatment. Treatment-related SAEs were attributed to any study drug.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Enzalutamide or Placebo Discontinuation - at PCD Cut-off Date of 31 January 2023	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)	An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day.
Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or Grade 4 Post-baseline in Hematology Laboratory Test Values - at PCD Cut-off Date of 31 January 2023	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)	Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Hematology laboratory abnormalities were graded according to CTCAE version 4.03 (Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death). This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from ≤Grade 2 at baseline to Grade 3 and Grade 4 post-baseline for the following parameters: hemoglobin, leukocytes, lymphocytes, neutrophils, platelets.
Number of Participants With Potentially Clinically Significant Vital Signs - at PCD Cut-off Date of 31 January 2023	From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98)	Participants with potentially clinically significant abnormalities in vital signs were summarized for the following parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Potentially clinically significant abnormalities were defined as (1) SBP (mmHg): \>180 and increase from baseline \>40; \<90 and decrease from baseline \>30; final visit or 2 consecutive visits change from baseline (CFB) ≥10, ≥15, ≥20; final visit or most extreme result ≥140, ≥180, ≥140 and ≥20 CFB, ≥180 and ≥20 CFB; (2) DBP (mmHg): \>105 and increase from baseline \>30; \<50 and decrease from baseline \>20; final visit or 2 consecutive visits CFB ≥5, ≥10, ≥15; final visit or most extreme result ≥90, ≥105, ≥90 and ≥15 CFB, ≥105 and ≥15 CFB; (3) HR (bpm): \>120 and increase from baseline \>30; \<50 and decrease from baseline \>20.

Trial Locations

Locations (243): MILAB
🇸🇰
Presov, Slovakia
Emory University Hospital
🇺🇸
Atlanta, Georgia, United States
Winship Cancer Institute, Emory University
🇺🇸
Atlanta, Georgia, United States
Northwestern Medical Group
🇺🇸
Chicago, Illinois, United States
Northwestern Memorial Hospital
🇺🇸
Chicago, Illinois, United States
First Urology, PSC
🇺🇸
Jeffersonville, Indiana, United States
The University of Kansas Hospital
🇺🇸
Kansas City, Kansas, United States
Kansas City Urology Care, PA
🇺🇸
Overland Park, Kansas, United States
Alliance Urology Specialists, PA
🇺🇸
Greensboro, North Carolina, United States
TriState Urologic Services PSC Inc., dba The Urology Group
🇺🇸
Cincinnati, Ohio, United States
Mercy Health Jewish Hospital
🇺🇸
Cincinnati, Ohio, United States
Clinical Research Solutions
🇺🇸
Middleburg Heights, Ohio, United States
Southwest Urology
🇺🇸
Middleburg Heights, Ohio, United States
Stephenson Cancer Center
🇺🇸
Oklahoma City, Oklahoma, United States
Oregon Imaging Center
🇺🇸
Eugene, Oregon, United States
Urologic Consultants of SE PA
🇺🇸
Bala-Cynwyd, Pennsylvania, United States
Keystone Urology Specialists
🇺🇸
Lancaster, Pennsylvania, United States
Genesis Cancer Care NSW
🇦🇺
Gateshead, New South Wales, Australia
Icon Cancer Care South Brisbane
🇦🇺
South Brisbane, Queensland, Australia
Icon Cancer Foundation
🇦🇺
South Brisbane, Queensland, Australia
Icon Cancer Centre Southport
🇦🇺
Southport, Queensland, Australia
Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
Box Hill Hospital
🇦🇺
Box Hill, Victoria, Australia
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
Austin Health
🇦🇺
Heidelberg, Victoria, Australia
Australian Urology Associates
🇦🇺
Malvern, Victoria, Australia
Sunshine Hospital
🇦🇺
St Albans, Victoria, Australia
Fiona Stanley Hospital
🇦🇺
Murdoch, Western Australia, Australia
Fundacao Pio XII - Hospital de Cancer de Barretos
🇧🇷
Barretos, SP, Brazil
Hospital das Clinicas da Faculdade de Ciencias Medicas da UNICAMP
🇧🇷
Campinas, SP, Brazil
Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
🇧🇷
Santo Andre, SP, Brazil
Oncosite - Centro de Pesquisa Clinica em Oncologia Ltda
🇧🇷
Ijuí/RS, Brazil
Prostate Cancer Centre
🇨🇦
Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦
Edmonton, Alberta, Canada
Vancouver Prostate Centre
🇨🇦
Vancouver, British Columbia, Canada
Manitoba Prostate Centre CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Nova Scotia Health Authority
🇨🇦
Halifax, Nova Scotia, Canada
The Male/Female Health and Research Centre, Royal Court Medical Centre
🇨🇦
Barrie, Ontario, Canada
Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
Seinaejoen Keskussairaala
🇫🇮
Seinaejoki, Finland
Tampereen yliopistollinen sairaala
🇫🇮
Tampere, Finland
ICO- site Paul Papin
🇫🇷
Angers cedex 09, France
Clinique Pasteur - Lanroze Service Pharmacie
🇫🇷
Brest, France
Clinique Pasteur - Lanroze
🇫🇷
Brest, France
CHD Vendée
🇫🇷
LA ROCHE SUR YON cedex 9, France
CHRU de Lille - Hopital Claude Huriez
🇫🇷
Lille cedex, France
ICM Val d'Aurelle
🇫🇷
Montpellier Cedex 5, France
CHU de Nantes - Hotel Dieu
🇫🇷
Nantes, France
Hopital Saint-Louis
🇫🇷
Paris cedex 10, France
Institut Mutualiste Montsouris
🇫🇷
Paris Cedex 14, France
CHP Saint-Gregoire
🇫🇷
Saint-Gregoire, France
ICO - site Rene Gauducheau
🇫🇷
Saint-Herblain cedex, France
Hia Begin
🇫🇷
Saint-Mande, France
Hopital Foch
🇫🇷
Suresnes, France
Institut Gustave Roussy
🇫🇷
Villejuif, France
Farmacia, Azienda Socio Sanitaria Territoriale di Cremona
🇮🇹
Cremona, Italy
Akademiska sjukhuset
🇸🇪
Uppsala, Sweden
Univerzitna nemocnica Martin
🇸🇰
Martin, Slovakia
UROEXAM, spol. s r.o.
🇸🇰
Nitra, Slovakia
Fakultna nemocnica s poliklinikou Zilina
🇸🇰
Zilina, Slovakia
Icon Cancer Care Wesley
🇦🇺
Auchenflower, Queensland, Australia
Lakeland Regional Health Hollis Cancer Center
🇺🇸
Lakeland, Florida, United States
The Urology Center of Colorado
🇺🇸
Denver, Colorado, United States
Foothills Urology, P.C.
🇺🇸
Golden, Colorado, United States
Satakunnan Keskussairaala
🇫🇮
Pori, Finland
The University of Kansas Cancer Center and Medical Pavilion
🇺🇸
Westwood, Kansas, United States
Eastern Connecticut Hematology Oncology Associates
🇺🇸
Norwich, Connecticut, United States
Oregon Urology Institute
🇺🇸
Springfield, Oregon, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of Alabama at Birmingham, IDS Pharmacy
🇺🇸
Birmingham, Alabama, United States
Alaska Urological Institute dba Alaska Clinical Research Center
🇺🇸
Anchorage, Alaska, United States
Urological Associates of Southern Arizona, PC
🇺🇸
Tucson, Arizona, United States
Tower Hematology Oncology Medical Group
🇺🇸
Beverly Hills, California, United States
Cedars-Senai OCC Pharmacy
🇺🇸
Los Angeles, California, United States
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
🇺🇸
Los Angeles, California, United States
University of California, Irvine Medical Center
🇺🇸
Orange, California, United States
Sutter Medical Group, Vascular & Varicose Vein Center
🇺🇸
Roseville, California, United States
Sutter Medical Group
🇺🇸
Roseville, California, United States
UC Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
University of California Davis Medical Center
🇺🇸
Sacramento, California, United States
University of California, Davis, School of Medicine
🇺🇸
Sacramento, California, United States
GU Research Network/Wichita Urology Group
🇺🇸
Wichita, Kansas, United States
John Hopkins University Hospital
🇺🇸
Baltimore, Maryland, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸
Baltimore, Maryland, United States
The Sidney Kimmel Cancer Center at Johns Hopkins Hospital- Oncology Investigational Drug Services
🇺🇸
Baltimore, Maryland, United States
Chesapeake Urology Research Associates
🇺🇸
Towson, Maryland, United States
Comprehensive Urology - Macomb Office
🇺🇸
Macomb, Michigan, United States
Comprehensive Urology - Royal Oak (Stephenson) office
🇺🇸
Royal Oak, Michigan, United States
GU Research Network, LLC / Urology Cancer Center
🇺🇸
Omaha, Nebraska, United States
VA Lahontan Valley Outpatient Clinic
🇺🇸
Fallon, Nevada, United States
Memorial Sloan Kettering Cancer Center Basking Ridge
🇺🇸
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center Commack
🇺🇸
Commack, New York, United States
Memorial Sloan Kettering Cancer Center Westchester
🇺🇸
Harrison, New York, United States
Memorial Hospital
🇺🇸
New York, New York, United States
Sidney Kimmel Center for Prostate and Urologic Cancers
🇺🇸
New York, New York, United States
Premier Medical Group of the Hudson Valley PC
🇺🇸
Poughkeepsie, New York, United States
Memorial Sloan Kettering Cancer Center Rockville Centre
🇺🇸
Rockville Centre, New York, United States
Associated Medical Professionals of New York, PLLC
🇺🇸
Syracuse, New York, United States
Memorial Sloan Kettering Cancer Center Nassau
🇺🇸
Uniondale, New York, United States
Duke Investigational Chemotherapy Services
🇺🇸
Durham, North Carolina, United States
Duke Nuclear Medicine
🇺🇸
Durham, North Carolina, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
🇺🇸
Philadelphia, Pennsylvania, United States
Honickman Centre
🇺🇸
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital, Bodine Buiding
🇺🇸
Philadelphia, Pennsylvania, United States
Thomas Jefferson University, Medical Oncology
🇺🇸
Philadelphia, Pennsylvania, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Carolina Urologic Research Center
🇺🇸
Myrtle Beach, South Carolina, United States
Vanderbilt Unversity Medical Center, Dept. of Urologic Surgery
🇺🇸
Nashville, Tennessee, United States
Vanderbilt Unversity Medical Center, The Urology Clinic
🇺🇸
Nashville, Tennessee, United States
Urology Clinics of North Texas, PLLC
🇺🇸
Dallas, Texas, United States
Houston Metro Urology
🇺🇸
Houston, Texas, United States
Urology San Antonio Research
🇺🇸
San Antonio, Texas, United States
Henrico Doctor's Hospital
🇺🇸
Henrico, Virginia, United States
Virginia Urology
🇺🇸
Richmond, Virginia, United States
Urology of Virginia, PLLC.
🇺🇸
Virginia Beach, Virginia, United States
Lismore Base hospital
🇦🇺
Lismore, New South Wales, Australia
Liverpool Hospital
🇦🇺
Liverpool, New South Wales, Australia
Macquarie University
🇦🇺
North Ryde, New South Wales, Australia
Genesis Cancer Care
🇦🇺
North Sydney, New South Wales, Australia
Port Macquarie Base Hospital
🇦🇺
Port Macquarie, New South Wales, Australia
GenesisCare North Shore
🇦🇺
St Leonards, New South Wales, Australia
The Tweed Hospital
🇦🇺
Tweed Heads, New South Wales, Australia
Australian Clinical Trials Pty Ltd
🇦🇺
Wahroonga, New South Wales, Australia
Sydney Adventist Hospital
🇦🇺
Wahroonga, New South Wales, Australia
Calvary Mater Newcastle
🇦🇺
Waratah, New South Wales, Australia
Westmead Hospital
🇦🇺
Westmead, New South Wales, Australia
Illawarra Cancer Care Centre
🇦🇺
Wollongong, New South Wales, Australia
Crown Princess Mary Cancer Centre
🇦🇺
Westmead, NEW, Australia
Icon Cancer Care Chermside
🇦🇺
Chermside, Queensland, Australia
Hospital Barmherzige Schwestern Linz
🇦🇹
Linz, Upper Austria, Austria
Hospital Barmherzige Schwestern Linz, Department of Urology
🇦🇹
Linz, Austria
Ordensklinikum Linz GmbH
🇦🇹
Linz, Austria
Department of Nuclear Medicine and Endocrinology, University Hospital Salzburg, Austria
🇦🇹
Salzburg, Austria
Department of Radiology, University Hospital Salzburg, Austria
🇦🇹
Salzburg, Austria
Department of Urology,Paracelsus Medical University Salzburg
🇦🇹
Salzburg, Austria
AKH - Medizinische Universität Wien
🇦🇹
Vienna, Austria
Department of Internal Medicine I, Medical university Vienna
🇦🇹
Vienna, Austria
Hospital São Rafael S.A
🇧🇷
Salvador, BA, Brazil
Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner
🇧🇷
Curitiba, Parana, Brazil
CITO - Centro Integrado de Terapia Onco-Hematologica - Hospital de Clinicas de Passo Fundo
🇧🇷
Passo Fundo, RS, Brazil
Hospital de Clinicas de Porto Alegre
🇧🇷
Porto Alegre, RS, Brazil
CLINIONCO - Clinica de Oncologia de Porto Alegre Ltda.
🇧🇷
Porto Alegre, RS, Brazil
Hospital Sao Lucas da PUCRS
🇧🇷
Porto Alegre, RS, Brazil
Centre for Applied Urological Research
🇨🇦
Kingston, Ontario, Canada
Hotel Dieu Hospital
🇨🇦
Kingston, Ontario, Canada
Urology Associates/ Urologic Medical Research
🇨🇦
Kitchener, Ontario, Canada
London Health Sciences Centre - Victoria Hospital
🇨🇦
London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
University Health Network - Princess Margaret Cancer Centre
🇨🇦
Toronto, Ontario, Canada
Urology South Shore Research
🇨🇦
Greenfield Park, Quebec, Canada
Centre Hospitalier de l'Universite de Montreal
🇨🇦
Montreal, Quebec, Canada
McGill University Health Centre
🇨🇦
Montreal, Quebec, Canada
Ultra-Med Inc.
🇨🇦
Pointe-Claire, Quebec, Canada
CHU de Quebec - L'Hotel-Dieu de Quebec
🇨🇦
Quebec, Canada
CHU de Quebec - L'Hotel-Dieu de Quebec - CRCEO
🇨🇦
Quebec, Canada
Aarhus University Hospital
🇩🇰
Arhus N, Denmark
Rigshospitalet - Copenhagen University Hospital
🇩🇰
Copenhagen, Denmark
Rigshospitalet, Dept of Radiology
🇩🇰
Copenhagen, Denmark
Odense University Hospital
🇩🇰
Odense C, Denmark
Vejle Sygehus
🇩🇰
Vejle, Denmark
Helsingin yliopistollinen keskussairaala
🇫🇮
Helsinki, Finland
Oulun yliopistollinen sairaala
🇫🇮
Oulu, Finland
Struttura Complessa di Oncologia, Azienda Socio Sanitaria Territoriale di Cremona
🇮🇹
Cremona, Italy
UO di Radiologia, Azienda Socio Sanitaria Territoriale di Cremona
🇮🇹
Cremona, Italy
UO di Oncologia,Ospedale Civile degli Infermi
🇮🇹
Faenza RA, Italy
UO di Radiologia, Ospedale Civile degli Infermi
🇮🇹
Faenza RA, Italy
UO di Oncologia, Ospedale Civile Umberto I
🇮🇹
Lugo RA, Italy
Uo di Radiologia, Ospedale Civile Umberto I
🇮🇹
Lugo RA, Italy
Laboratorio Farmaci Antiblastici, IRCCS Istituto
🇮🇹
Meldola (FC), Italy
U.O. Oncologia Medica, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹
Meldola (FC), Italy
UO Radiologia,IRCCS Istituto Scientifico Romagnolo Per lO Studio e la Cura dei Tumori (IRST)
🇮🇹
Meldola (FC), Italy
Istituto Nazionale Tumori Fondazione G. Pascale/Oncologia Medica A
🇮🇹
Napoli, Italy
S.C.D.U. Oncologia Medica, A.O.U. San Luigi Gonzaga
🇮🇹
Orbassano (TO), Italy
S.C.D.U. Radiodiagnostica, A.O.U. San Luigi Gonzaga
🇮🇹
Orbassano (TO), Italy
Servizio di Farmacia, Ospedale Santa Maria delle Croci
🇮🇹
Ravenna, Italy
Servizio di Radiologia, Ospedale Santa Maria Delle Croci
🇮🇹
Ravenna, Italy
UO di Oncologia Medica, Ospedale Santa Maria delle Croci
🇮🇹
Ravenna, Italy
Farmacia Interna, Ospedale degli Infermi
🇮🇹
Rimini, Italy
UO Oncologia, Ospedale degli Infermi
🇮🇹
Rimini, Italy
Azienda Ospedaliera S, Camillo Forlanini, UOC per il governo clinico in Oncologia Medica,pad,Flajani
🇮🇹
Roma, Italy
U.O. di Oncologia Medica, Ospedale Santa Chiara
🇮🇹
Trento, Italy
U.O. Medicina Nucleare, Ospedale Santa Chiara
🇮🇹
Trento, Italy
U.O. Radiologia, Ospedale Santa Chiara
🇮🇹
Trento, Italy
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Gyeonggi-do, Korea, Republic of
Pusan National University Yangsan Hospital
🇰🇷
Yangsan-si, Gyeongsangnam-do, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷
Hwasun-gun, Jeollanam-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷
Incheon, Korea, Republic of
Severance Hospital. Yonsei University Health System
🇰🇷
Seoul, Korea, Republic of
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Gangnam Severance Hospital, Yonsei University Health System
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
VU Medical Centrum, Department of Urology
🇳🇱
Amsterdam, Netherlands
Academisch Medisch Centrum
🇳🇱
Amsterdam, Netherlands
Gelderse Vallei Ziekenhuis
🇳🇱
Ede, Netherlands
Catharina Ziekenhuis Eindhoven
🇳🇱
Eindhoven, Netherlands
University Medical Centrum Groningen, Department Urologie
🇳🇱
Groningen, Netherlands
Medisch Centrum Leeuwarden
🇳🇱
Leeuwarden, Netherlands
Maastricht University Medical Center, Department of Urology
🇳🇱
Maastricht, Netherlands
Antonius Ziekenhuis
🇳🇱
Sneek, Netherlands
Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii
🇵🇱
Gdansk, Poland
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o. o.
🇵🇱
Slupsk, Poland
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o., Oddzial Urologiczny
🇵🇱
Slupsk, Poland
Kujawsko-Pomorskie Centrum Urologicznw Sp z o.o
🇵🇱
Torun, Poland
Centrum Medyczne Melita Medical
🇵🇱
Wroclaw, Poland
EMC Instytut Medyczny Spolka Akcyjna
🇵🇱
Wroclaw, Poland
Fakultna nemocnica s poliklinikou F.D.Roosevelta
🇸🇰
Banska Bystrica, Slovakia
CUIMED, s.r.o., Urologicka ambulancia
🇸🇰
Bratislava, Slovakia
Vychodoslovensky onkologicky ustav, a.s.
🇸🇰
Kosice, Slovakia
Althaia, Xarxa Assistencial Universitària de Manresa
🇪🇸
Manresa, Barcelona, Spain
Hospital Universitari Son Espases
🇪🇸
Palma de Mallorca, Islas Baleares, Spain
Complejo Hospitalario Universitario de Santiago
🇪🇸
Santiago de Compostela, LA Coruna, Spain
Hospital del Mar
🇪🇸
Barcelona, Spain
Hospital Clinic i Provincial de Barcelona, Dr. Antonio Alcaraz Asensio
🇪🇸
Barcelona, Spain
Hospital Universitario Puerta del Mar
🇪🇸
Cadiz, Spain
ICO Girona; Hospital Universitari de Girona Dr. Josep Trueta. Servicio de Oncologia
🇪🇸
Girona, Spain
Hospital Universitario de La Princesa
🇪🇸
Madrid, Spain
Hospital General Universitario Gregorio Maranon. Servicio de Oncologia.
🇪🇸
Madrid, Spain
Centro Oncologico MD Anderson International Espana
🇪🇸
Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸
Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Complejo Hospitalario Universitario de Orense
🇪🇸
Orense, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸
Sabadell, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸
Salamanca, Spain
Instituto Valenciano de Oncologia IVO
🇪🇸
Valencia, Spain
Sahlgrenska Universitetssjukhuset, Sahlgrenska
🇸🇪
Goteborg, Sweden
Skanes Universitetssjukhus
🇸🇪
Malmo, Sweden
Universitetssjukhuset Orebro
🇸🇪
Orebro, Sweden
Sodersjukhuset AB
🇸🇪
Stockholm, Sweden
Karolinska Universitetssjukhuset Solna
🇸🇪
Stockholm, Sweden
Norrlands Universitetssjukhus
🇸🇪
Umea, Sweden
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳
Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳
Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳
Taoyuan, Taiwan
Ross Hall Hospital
🇬🇧
Glasgow, CITY OF Glasgow, United Kingdom
Royal Devon & Exeter Hospital
🇬🇧
Wonford, Devon, United Kingdom
Royal Free Hospital
🇬🇧
London, Greater London, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧
Sutton, Surrey, United Kingdom
Cancer Centre, Queen Elizabeth Hospital
🇬🇧
Birmingham, WEST Midlands, United Kingdom
University Hospitals Bristol NHS Foundation Trust
🇬🇧
Bristol, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧
Glasgow, United Kingdom