Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer
- Conditions
- Metastatic Prostate Cancer
- Interventions
- Registration Number
- NCT03072238
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of ipatasertib plus abiraterone and prednisone/prednisolone compared with placebo plus abiraterone and prednisone/prednisolone in participants with metastatic castrate-resistant prostate cancer (mCRPC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 1101
- Eastern Collaborative Oncology Group (ECOG) performance status of 0 or 1 at screening
- Adequate hematologic and organ function within 28 days before the first study treatment
- Ability to comply with the study protocol, in the investigator's judgment
- Willingness and ability of participants to use the electronic device to report selected study outcomes; Caregivers and site staff can assist with patient diary input but patient must be able to independently comprehend and answer the questionnaires
- Life expectancy of at least 6 months
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
- For enrollment into the China extension cohort, residence in the People's Republic of China
Disease-specific Inclusion Criteria:
- Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small-cell features
- Consent to provide a formalin-fixed paraffin-embedded (FFPE) tissue block (preferred) or a minimum of 15 (20 preferred) freshly cut unstained tumor slides from the most recently collected, available tumor tissue accompanied by an associated pathology report (with tumor content information, Gleason score, and disease staging) for PTEN IHC and NGS testing and for other protocol-mandated secondary and exploratory assessments. If only 12-14 slides are available, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor. Cytologic or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases is not acceptable
- A valid PTEN IHC result (testingcentral laboratory tested with results directly sent to IxRS) (e.g., participants with an "invalid" or "failed" PTEN IHC result are not permitted to enroll)
- Metastatic disease documented prior to randomization by clear evidence of bone lesions on bone scan and/or measurable soft tissue disease by computed tomography (CT) and/or magnetic resonance imaging (MRI) (at least one target lesion) according to RECIST v1.1
- Asymptomatic or mildly symptomatic form of prostate cancer
- Progressive disease before initiating study treatment
- Ongoing androgen deprivation with gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy, with serum testosterone <= 50 ng/dL (<= 1.7 nmol/L) within 28 days before randomization
- Inability or unwillingness to swallow whole pills
- History of malabsorption syndrome or other condition that would interfere with enteral absorption
- Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including cirrhosis, current alcohol abuse, or current known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Need of more than 10 mg/day of prednisone or an equivalent dose of other anti-inflammatory corticosteroids as a current systemic corticosteroid therapy to treat a chronic disease (e.g., rheumatic disorder)
- Active infection requiring intravenous (IV) antibiotics within 14 days before Day 1, Cycle 1
- Immunocompromised status because of current known active infection with HIV or because of the use of immunosuppressive therapies for other conditions
- Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, Cycle 1, or anticipation of the need for major surgery during study treatment
- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), untreated coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), myocardial infarction or atrial thrombotic events within the past 6 months, severe unstable angina, New York Heart Association Class III and IV heart disease or depressed left ventricular ejection fraction (LVEF; previously documented LVEF < 50% without documentation of recovery), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
- History of another malignancy within 5 years prior to randomization, except for either adequately treated non-melanomatous carcinoma of the skin, adequately treated melanoma in situ, adequately treated non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta, and low grade T1 tumors), or other malignancies where the patient has undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to have a recurrence rate of <5% at 5 years
- Any other diseases, cardiovascular, pulmonary, or metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participants at high risk from treatment complications.
Disease-Specific Exclusion Criteria:
- Pathologic findings consistent with small-cell or neuroendocrine carcinoma of the prostate
- Any therapy including chemotherapy (e.g., docetaxel) or biological therapy (e.g., vaccine, immunotherapy) for the treatment of castration-resistant prostate cancer. Previous treatment with flutamide, steroidal anti-androgens, androgens, estrogens, bicalutamide, nilutamide, or 5-α reductase inhibitor is permitted.
- Use of opioid medications for cancer-related pain, including codeine and dextropropoxyphene, currently or any time within 4 weeks of Day 1, Cycle 1
- Prior treatment with abiraterone or other known potent CYP17 inhibitors (e.g., ketoconazole, orteronel) or investigational agents that block androgen synthesis. Previous treatment with itraconazole and fluconazole is permitted.
- Prior treatment with enzalutamide or other potent androgen-receptor blockers, approved or experimental (e.g., ARN-509, ODM-201, or galeterone)
- Prior treatment with flutamide (Eulexin®), steroidal anti-androgens (e.g., cyproterone acetate, chlormadinone acetate), androgens, or estrogens treatment within 4 weeks of Cycle 1, Day 1
- Prior treatment with bicalutamide (Casodex®) or nilutamide (Nilandron®) within 6 weeks of Cycle 1, Day 1
- Prior treatment with 5-alpha reductase inhibitors within 4 weeks of Cycle 1, Day 1
- Prior treatment with systemic radiopharmaceuticals (e.g., radium-223 and strontium-89). Radiopharmaceuticals for the purpose of imaging are permitted. Focal palliative radiation to treat cancer-related pain is permitted provided that the last treatment with radiation is at least 14 days prior to Cycle 1, Day 1.
- Prior treatment with approved or experimental therapeutic agents with known inhibition of the PI3K pathway, including PI3K inhibitors, AKT inhibitors, and mTOR inhibitors
- Administration of an investigational therapeutic agent within 28 days of Cycle 1, Day 1
- Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsant medications or corticosteroids for symptomatic control); a CT or MRI scan of the brain will be performed at screening if required by the local health authority
- Any chronic therapy or use of food supplements that are strong CYP3A4/5 inducers or inhibitors or sensitive substrates of CYP3A or CYP2D6 with a narrow therapeutic window
Abiraterone-Specific Exclusion Criteria:
- Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg)
- History of pituitary or adrenal dysfunction
- Any ongoing cardiac arrhythmias (including atrial fibrillation) that require medical therapy
Ipatasertib-Specific Exclusion Criteria:
- Type 1 or Type 2 diabetes mellitus requiring insulin at study entry
- History of inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis), active bowel inflammation (e.g., diverticulitis)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Abiraterone Prednisone/Prednisolone Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles. Placebo + Abiraterone Abiraterone Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles. Placebo + Abiraterone Placebo Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles. Ipatasertib + Abiraterone Prednisone/Prednisolone Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles. Ipatasertib + Abiraterone Abiraterone Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles. Ipatasertib + Abiraterone Ipatasertib Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
- Primary Outcome Measures
Name Time Method Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (PTEN Loss Population) Up to approximately 31 months Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the sum of diameters of target lesions; progression of non target lesions; the appearance of one or more new lesions. Disease progression for bone lesions is defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. rPFS will be analyzed in participants with phosphatase and tensin homolog (PTEN) - loss tumors (using the Ventana PTEN immunohistochemistry (IHC) assay).
Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (Intent-To-Treat (ITT) Population) Up to approximately 31 months Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the sum of diameters of target lesions; progression of non target lesions; the appearance of one or more new lesions. Disease progression for bone lesions is defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later. rPFS will be analyzed in the Intent-to-Treat (ITT) population.
- Secondary Outcome Measures
Name Time Method Time to First Opioid Use Up to approximately 7 years Time to first opioid use is defined as the documentation of the first opioid prescription for cancer-related pain followed by the participant's record of opioid intake or availability of an Analgesic Quantification Algorithm (AQA) daily score. Participants reporting use of opioid for cancer-related pain at baseline will be excluded from the analysis. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Investigator-Assessed rPFS Per PCWG3 Criteria in Participants With PTEN-Loss Tumors by Next-Generation Sequencing (NGS) Up to approximately 7 years Investigator-assessed rPFS is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first and will be analyzed in participants with PTEN-loss tumors by NGS. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Plasma Concentrations of Abiraterone at Specified Timepoints Pre-dose at steady state in Cycle 1, Day 15 and Cycle 3 Day 1 (each cycle length= 28 days) Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Objective Response Rate (ORR) Up to approximately 7 years An objective response is defined as a complete response (CR) or partial response (PR) on two consecutive occasions \>=4 weeks apart, as determined by the investigator using RECIST v1.1 and PCWG3 criteria, in participants with measurable disease at baseline. Participants without a post-baseline tumor assessment will be considered non-responders. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Duration of Response (DOR) Up to approximately 7 years Duration of Response (DOR) is defined as the time from first occurrence of a documented confirmed objective response until the time of documented disease progression as determined by the investigator using RECIST v1.1 and PCWG3 criteria, or death from any cause, whichever occurs first. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time to Function Deterioration Up to approximately 7 years Time to function deterioration was defined as the time from the date of randomisation to the date of 10-point or more decrease on either the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) PF (Physical Functioning) or RF (Role Functioning) scale scores (range, 0-100) held for two consecutive assessments, or a 10 point or more score decrease followed by death (any cause) within 28 days, whichever occurs first. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Plasma Concentrations of Ipatasertib at Specified Timepoints 1-3 hours post-dose (Cycle 1, Day 1; Cycle 1 Day 15 and Cycle 3 Day 1) and pre-dose at steady state (Cycle 1 Day 15, Cycle 3 Day 1, Cycle 6 Day 1) (each cycle length= 28 days) Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Overall Survival (OS) Up to approximately 7 years Overall Survival (OS) is defined as the time from randomization to death due to any cause. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time to Symptomatic Skeletal Event (SSE) Up to approximately 7 years Time to SSE is defined as the time interval from the date of randomization to the date of an SSE. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time to Pain Progression Up to approximately 7 years Time to pain progression was defined as the time from randomization to the first occurrence of confirmed clinically meaningful cancer-related pain progression event. Cancer-related pain progression refers to pain onset for participants who are asymptomatic at baseline or pain worsening for those who are mildly symptomatic at baseline. Pain severity will be graded on a 10-point scale, with 0=no pain and 10=severe pain. Pain severity progression is defined as a ≥ 2-point absolute increase from baseline. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time to Initiation of Cytotoxic Chemotherapy Up to approximately 7 years Time to initiation of cytotoxic chemotherapy is defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for prostate cancer. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Time to Prostate-Specific Antigen (PSA) Progression Up to approximately 7 years Time to PSA progression is defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression is defined as a PSA increase that is ≥ 25% and ≥ 2 ng/mL above the baseline or the nadir, which is confirmed by a second value ≥ 3 weeks later. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
PSA Response Rate Up to approximately 7 years PSA response rate is defined as the percentage of participants achieving a PSA decline ≥50% from baseline. Participants without a post-baseline PSA assessment will be considered non-responders. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Percentage of Participants With Adverse Events (AEs) Baseline up until 28 days after the last dose of study drug or initiation of subsequent lines of anti-cancer therapy, whichever occurs first (up to a maximum of 7 years). An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events. Data collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.
Trial Locations
- Locations (184)
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
USC Norris Cancer Center
🇺🇸Los Angeles, California, United States
Medical Care & Research
🇲🇽Mérida, Yucatan, Mexico
SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego
🇵🇱Opole, Poland
Health Pharma Professional Research
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
Consultorio de Especialidad en Urologia Privado
🇲🇽Durango, Mexico
Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Nowotworow Ukladu Moczowego
🇵🇱Warszawa, Poland
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial; Servicio de Urología
🇪🇸Barcelona, Spain
Sykehuset Østfold Kalnes; Onkologisk seksjon
🇳🇴Grålum, Norway
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
🇪🇸Malaga, Spain
Hospital Clinico San Carlos; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
🇪🇸Sevilla, Spain
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Hospital Universitario Reina Sofia; Servicio de Oncologia
🇪🇸Córdoba, Cordoba, Spain
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain
Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
🇵🇱Warszawa, Poland
Addenbrookes Nhs Trust; Oncology Clinical Trials Unit
🇬🇧Cambridge, United Kingdom
Royal Marsden Hospital; Institute of Cancer Research
🇬🇧Sutton, United Kingdom
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
🇪🇸Madrid, Spain
Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii
🇵🇱Wroc?aw, Poland
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Chang Gung Memorial Hospital-LinKou; Urology
🇨🇳Taoyuan, Taiwan
Mount Vernon & Watford Trust Hospital; Dept. of Clinical Oncology
🇬🇧Northwood, United Kingdom
Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
🇹🇭Bangkok, Thailand
Chulalongkorn Hospital; Medical Oncology
🇹🇭Bangkok, Thailand
Royal Blackburn Hospital
🇬🇧Blackburn, United Kingdom
Royal Wolverhampton hospital; McHale Building
🇬🇧Wolverhampton, United Kingdom
Lynn Cancer Institute/Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, United States
Charleston Oncology, P .A
🇺🇸Charleston, South Carolina, United States
Eastern Health; GU - Oncology
🇦🇺Melbourne, Victoria, Australia
LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
🇦🇹Graz, Austria
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Woj. Wielospec. Centrum Onkologii i Traumatologii
🇵🇱?ód?, Poland
Russian Scientific Center of Roentgenoradiology
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Centro Medico Culiacan SA de CV; Consultorio Medico 303 B
🇲🇽Culiacan, Sinaloa, Mexico
Beijing Friendship Hospital Affiliated of Capital University of Medical Science
🇨🇳Beijing Shi, China
Pacific Hematology Oncology Associates
🇺🇸San Francisco, California, United States
Centre Antoine Lacassagne
🇫🇷Nice, France
Aarhus Universitetshospital, Urologisk Afd. K
🇩🇰Aarhus N, Denmark
Gunma University Hospital
🇯🇵Gunma, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Japan
Keio University Hospital
🇯🇵Tokyo, Japan
ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico
🇮🇹Napoli, Campania, Italy
University of Colorado Hospital - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Institut Mutualiste Montsouris; Oncologie
🇫🇷Paris, France
Rambam Health Care Campus; Oncology
🇮🇱Haifa, Israel
Mayo Clinic Arizona
🇺🇸Scottsdale, Arizona, United States
Ironwood Cancer & Research Centers
🇺🇸Chandler, Arizona, United States
Kaiser Permanente San Diego - Los Angeles
🇺🇸Los Angeles, California, United States
City of Hope
🇺🇸Duarte, California, United States
USC/Westside Cancer Ctr
🇺🇸Beverly Hills, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
Miami Cancer Institute of Baptist Health, Inc.
🇺🇸Miami, Florida, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Illinois Cancer Care
🇺🇸Peoria, Illinois, United States
Associates in Oncology/Hematology P.C.
🇺🇸Rockville, Maryland, United States
Karmanos Cancer Institute..
🇺🇸Detroit, Michigan, United States
Urology Cancer Center & GU Research Network
🇺🇸Omaha, Nebraska, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
HCA Midwest Division
🇺🇸Kansas City, Missouri, United States
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
🇺🇸Las Vegas, Nevada, United States
Northwest Cancer Specialists, P.C.
🇺🇸Tigard, Oregon, United States
Hackensack Univ Medical Center; John Theurer Cancer Ctr
🇺🇸Hackensack, New Jersey, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Oncology - Gulf Coast
🇺🇸The Woodlands, Texas, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Macquarie University Hospital
🇦🇺Macquarie Park, New South Wales, Australia
Monash Medical Centre; Oncology
🇦🇺Clayton, Victoria, Australia
Adelaide Cancer Centre
🇦🇺Kurralta Park, South Australia, Australia
Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie
🇦🇹Linz, Austria
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Landeskrankenhaus Salzburg; Universitätsklinik für Urologie und Andrologie der PMU
🇦🇹Salzburg, Austria
UZ Gent
🇧🇪Gent, Belgium
AZ Groeninge
🇧🇪Kortrijk, Belgium
CHU Sart-Tilman
🇧🇪Liège, Belgium
Hospital Luxemburgo; Oncologia
🇧🇷Belo Horizonte, MG, Brazil
Liga Norte Riograndense Contra O Câncer
🇧🇷Natal, RN, Brazil
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, RS, Brazil
BCCA-Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, Brazil
Lakeridge Health Oshawa; Oncology
🇨🇦Oshawa, Ontario, Canada
Hamilton Health Sciences - Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
CHU de Québec - Université Laval - Hôtel-Dieu de Québec
🇨🇦Quebec, Canada
Hopital Sacre-Coeur Research Centre
🇨🇦Montreal, Quebec, Canada
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing City, China
Jiangsu Cancer Hospital
🇨🇳Nanjing City, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai City, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Clinica CIMCA
🇨🇷San José, Costa Rica
ICIMED Instituto de Investigación en Ciencias Médicas
🇨🇷San José, Costa Rica
Odense Universitetshospital, Onkologisk Afdeling R
🇩🇰Odense C, Denmark
ICO Paul Papin; Oncologie Medicale.
🇫🇷Angers, France
Centre Jean Perrin
🇫🇷Clermont Ferrand, France
Centre Francois Baclesse; Oncologie
🇫🇷Caen, France
CHD Vendée
🇫🇷La Roche Sur Yon, France
Hopital Claude Huriez; Urologie
🇫🇷Lille, France
Institut régional du Cancer Montpellier
🇫🇷Montpellier, France
Institut de cancerologie du Gard
🇫🇷Nimes, France
CHU Poitiers
🇫🇷Poitiers, France
Hopital d'Instruction des Armees de Begin
🇫🇷Saint-Mande, France
Hopital Foch; Oncologie
🇫🇷Suresnes, France
IASO General Hospital of Athens
🇬🇷Athens, Greece
Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine
🇬🇷Athens, Greece
Institut Gustave Roussy; Departement Oncologie Medicale
🇫🇷Villejuif, France
Semmelwies University of Medicine; Urology Dept.
🇭🇺Budapest, Hungary
University Hospital of Patras Medical Oncology
🇬🇷Patras, Greece
Papageorgiou General Hospital; Medical Oncology
🇬🇷Thessaloniki, Greece
Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály
🇭🇺Budapest, Hungary
Budapesti Uzsoki Utcai Kórház
🇭🇺Budapest, Hungary
Cork University Hospital
🇮🇪Cork, Ireland
Debreceni Egyetem Klinikai Kozpont ; Department of Oncology
🇭🇺Debrecen, Hungary
Mater Misericordiae Uni Hospital; Oncology
🇮🇪Dublin, Ireland
Mater Private Hospital
🇮🇪Dublin, Ireland
Adelaide & Meath Hospital, Dublin, Incorporating the National Children's Hospital; Oncology Day Unit
🇮🇪Dublin, Ireland
Meir Medical Center; Oncology
🇮🇱Kfar-Saba, Israel
Belinson Medical Center, Division of Oncology
🇮🇱Petach Tikva, Israel
I.R.S.T Srl IRCCS; Oncologia Medica
🇮🇹Meldola, Emilia-Romagna, Italy
A.O. Universitaria Policlinico Di Modena; Oncologia
🇮🇹Modena, Emilia-Romagna, Italy
Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica
🇮🇹Roma, Lazio, Italy
A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia
🇮🇹Cremona, Lombardia, Italy
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
🇮🇹Milano, Lombardia, Italy
A.O. San Carlo Borromeo; U.O.C. Oncologia
🇮🇹Milano, Lombardia, Italy
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
🇮🇹Rozzano, Lombardia, Italy
Ospedale Area Aretina Nord; U.O.C. Oncologia
🇮🇹Arezzo, Toscana, Italy
Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
🇮🇹Firenze, Toscana, Italy
Ospedale di Trento-Presidio Ospedaliero Santa Chiara; Oncologia Medica
🇮🇹Trento, Trentino-Alto Adige, Italy
Nagoya University Hospital
🇯🇵Aichi, Japan
Hirosaki University Hospital
🇯🇵Aomori, Japan
National Cancer Center East
🇯🇵Chiba, Japan
Toho University Sakura Medical Center
🇯🇵Chiba, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵Hokkaido, Japan
Kanazawa University Hospital
🇯🇵Ishikawa, Japan
Yokohama City University Medical Center
🇯🇵Kanagawa, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Kitasato University Hospital
🇯🇵Kanagawa, Japan
Kochi Medical School Hospital
🇯🇵Kochi, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Toranomon Hospital
🇯🇵Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Kyorin University Hospital
🇯🇵Tokyo, Japan
Yamaguchi University Hospital
🇯🇵Yamaguchi, Japan
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Akershus universitetssykehus HF
🇳🇴Lørenskog, Norway
China Medical University Hospital; Urology
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital; Division of Urology
🇨🇳Taichung, Taiwan
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
B-A-Z County Hospital
🇭🇺Miskolc, Hungary
Chaim Sheba medical center, Oncology division
🇮🇱Ramat Gan, Israel
IPO do Porto; Servico de Oncologia Medica
🇵🇹Porto, Portugal
Altai Regional Oncological Center
🇷🇺Barnaul, Altaj, Russian Federation
Blokhin Cancer Research Center; Urological Dept
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Privolzhsk Regional Medical Center
🇷🇺Nizhny Novgorod, Niznij Novgorod, Russian Federation
Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
🇹🇭Bangkok, Thailand
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
🇪🇸Sabadell, Barcelona, Spain
Hospital Angeles Mocel
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
HUC; Servico de Urologia e Transplantacao Renal
🇵🇹Coimbra, Portugal
Hospital de Santa Maria; Servico de Oncologia Medica
🇵🇹Lisboa, Portugal
Moscow City Oncology Hospital #62
🇷🇺Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation
P.A. Herzen Oncological Inst. ; Oncology
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Hospital Universitario Son Espases; Servicio de Oncologia
🇪🇸Palma De Mallorca, Islas Baleares, Spain
Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit
🇹🇭Chiangmai, Thailand
Institut Catala d?Oncologia Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Insititut Catala D'Oncologia
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
KAOHSIUNG MEDICAL UNI CHUNG-HO HOSPITAL; Dept. Of Urology
🇨🇳Kaohsiung, Taiwan
Clinica Universitaria de Navarra; Servicio de Oncologia
🇪🇸Pamplona, Navarra, Spain
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States