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Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace the advice of a healthcare professional and should not be considered as a recommendation. Patients should always seek medical advice before making any decisions on their treatment. Healthcare Professionals should always refer to the specific labelling information approved for the patient's country or region. Data in this document or on the related website should not be considered as prescribing advice. The study listed may include approved and non-approved formulations or treatment regimens. Data may differ from published or presented data and are a reflection of the limited information provided here. The results from a single trial need to be considered in the context of the totality of the available clinical research results for a drug. The results from a single study may not reflect the overall results for a drug. The following information is the property of Bayer AG. Reproduction of all or part of this report is strictly prohibited without prior written permission from Bayer AG. Commercial use of the information is only possible with the written permission of the proprietor and is subject to a license fee. Please note that the General Conditions of Use and the Privacy Statement of bayer.com apply to the contents of this file.
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 1 of 10
Date of study report: 20 OCT 2016
Study title: Radium-223 Dichloride (Alpharadin) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients with Bone Metastasis
Sponsor’s study number:
16216
NCT number: NCT01618370
EudraCT number: 2012-000075-16
Sponsor: Bayer
Clinical phase: IIIb
Study objectives: To assess the acute and long-term safety of Radium RA 223 dichloride (Ra-223) dichloride
To assess the Overall Survival of this subject population
Test drug: Radium-223 dichloride (Xofigo; BAY 88-8223)
Name of active ingredient(s):
Radium-223 dichloride
Dose: 50 kBq/kg body weight
Route of administration:
Intravenous
Duration of treatment: Every 4 weeks for up to 6 cycles
Reference drug: Not applicable
Indication: Castration resistant (CR) / hormone refractory (HR) prostate cancer with bone metastasis
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Diagnosis and main criteria for
inclusion:
≥18 years with histologically or cytologically confirmed prostate cancer
Subjects diagnosed with progressive bone predominant metastatic CRPC/HRPC with at least two skeletal metastases on imaging with no lung, liver, and/or brain metastasis (lymph node only metastasis is allowed). A standard of practice bone scan for the documentation of at least 2 skeletal metastases can be used as long as it is within 3 months of planned start of treatment. If no bone scan within a 3 month window is available, then a technetium-99m bone scan will be obtained at screening (within 28 days of planned start of study drug)
o Progressive was defined as the appearance of new bone lesions or 2 subsequent increases in serum PSA over the previous reference value
No intention to use cytotoxic chemotherapy within the next 6 months
Adequate hematological, liver, and renal function
Life expectancy ≥6 months
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Study design: International, prospective, interventional, open-label, multi-center study
Methodology: During the treatment period, study medication was administered every 4 weeks. Patients were evaluated at each visit, prior to receiving Ra-223 Cl2 for treatment-emergent Grade 3-4 AEs, all treatment-emergent AEs of any grade leading to drug discontinuation, all grades of treatment-related AEs, serious adverse events (SAEs), skeletal-related events (SREs), laboratory values, ECOG performance status, and for changes in bone pain (quality of life [QoL]) as measured by patient assessment using a validated questionnaire. The term skeletal-related event is used in this clinical study report (CSR) to mean the same as the newer term symptomatic skeletal event (SSE). During the follow-up period, patients were evaluated every 6 months for long-term safety including hematologic effects of Ra-223 Cl2 on peripheral blood counts, SREs, treatment-related AEs and SAEs, and occurrence of secondary malignancies. If the patient could no longer travel to the clinical site, he was followed up for survival, additional malignancies including acute myeloid leukemia (AML), hematological conditions such as myelodysplastic syndrome (MDS), aplastic anemia, myelofibrosis etc, and information on additional anti-cancer treatments received treatment with Ra-223 Cl2, seriousness, Common Terminology Criteria for Adverse Events (CTCAE) v4.03 grading, action taken,and outcome.
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Study center(s): 115 study centers in 15 countries: Belgium (5 centers), Canada (5 centers), Germany (20 centers), Spain (19 centers), Finland (5 centers), Great Britain (8 centers), Ireland (3 centers), Israel (8 centers), Italy (13 centers), Netherlands (2 centers), Norway (5 centers), Poland (2 centers), Sweden (10 centers), Switzerland (8 centers), Russia (2 centers)
Publication(s) based on the study (references):
Saad F, Carles J, Gillessen S, Heidenreich A, Heinrich D, Gratt J, et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol. 2016 17(9): 1306-16.
Study period: Study Start Date: 22 JUL 2012
Study Completion Date: 28 FEB 2016
Early termination: Not applicable
Number of subjects:
Planned: 1500
Analyzed: 708
Criteria for evaluation
Efficacy:
Overall survival, defined as the time in months from the start of therapy to death, due to any cause. Patients alive at the time of analysis were censored at the last date known to be alive.
Time to disease progression, defined as the time in months from the start of therapy to the date that disease progression was assessed per the local standard of care.
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Safety:
ECOG performance status (PS) o Changes in PS from baseline on the ECOG scale to the PS
severity at each cycle, end of treatment, follow-up, and end of follow-up were tabulated by the number and percentage of patients in each shift change category.
o A patient was categorized as having a PS response or progression depending on whether there was an improvement or worsening, respectively, by 1 point or more on the ECOG scale from the baseline value.
Additional malignancies o Summary of additional primary malignancies was presented
by system organ class and preferred term. AML and MDS classifications were tabulated for each classification.
Adverse events o Adverse events of interest were those Common Terminology
Criteria for Adverse Events (CTCAE) Grade 3 to 5 treatment-related hematological and gastrointestinal AEs.
Clinical laboratory parameters
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Statistical methods: All data were summarized descriptively.
Substantial protocol changes:
Protocol amendment 1 from 30 OCT 2012 introduced the following changes:
Changed Radium-223 Chloride and Ra223 Cl to Radium- 223 Dichloride and Ra-223 Cl2 respectively, following receipt of the official United States Adopted Name for the product
Clarification on the inclusion/exclusion criteria particularly the definition of progressive disease and acceptable diagnostic procedures
Inclusion of subjects with history of spinal cord compression who have completely recovered
Inclusion of allowed concomitant treatments, abiraterone and denosumab
Extension of the screening period from 21 days to 28 days and extension of the timeframe for laboratory assessments from 24 hours to within 72 hours
Addition of long-term follow-up section
Protocol amendment 2 from 02 APR 2013 introduced the following changes:
Exclusion from the active follow up of subjects who receive further anticancer treatment including radium 223 dichloride administered either within a clinical study or as commercially available drug, and to follow them up for survival status only.
Addition of a time window of 3 months for bone scan due to differences in the standard of care in the involved sites Provide clarifications and guidance on:
o Washout period of 4 weeks applicable for all prior anticancer therapies
o Anticancer therapies allowed during the study treatment period
o Guidance on when rescreening is allowed
o Definition of end of screening period
o Reconfirmation of eligibility
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Substantial protocol changes
(continued):
Protocol amendment 3 from 24 JUN 2014, was locally valid only for centers located in Germany; it specified the following modification:
The German Radioprotection Agency, Bundesamt für Strahlenschutz (BfS), mandated that all German subjects enrolled in study 16216 have a long-term follow up of at least 5 years to collect data on long term effects of radium 223 dichloride. A separate, extended safety follow up protocol was set up.
Subject disposition and baseline
Overall, 852 subjects were enrolled in the study, and 708 of these subjects entered the Treatment Period and were administered at least one dose of radium-223 dichloride. The remaining 143 subjects were not treated and were discontinued at screening.
Efficacy The efficacy results at the end of study (Last patient last visit [LPLV] 28 FEB 2016) were consistent with those reported at primary completion (data cutoff date 21 NOV 2014; Report PH-38015). By the end of the study, 421 (59.5%) subjects had experienced disease progression. The median time to disease progression was 5.8 months. At primary completion (data cutoff date 21 NOV 2014; Report PH-38015), 410 (58.9%) subjects had experienced disease progression. The median time to disease progression was 6 months. By the end of the study, 224 (31.6%) subjects had died. The median overall survival (OS) was 16 months.
At primary completion (data cutoff date 21 NOV 2014; Report PH-38015), 210 (30.2%) subjects had died. The median OS was 16 months. .
At the end of study, total of 145 (20.5%) subjects experienced SREs during the study, of whom 107 (15.1%) received external beam radiotherapy for bone pain. The median time to SRE and median time to external beam radiotherapy could not be fully computed because of the small number of events recorded due to the short follow up.
At primary completion (data cutoff date 21 NOV 2014; Report PH-38015), 143 (20.5%) subjects experienced SREs of whom 105 (15.1%) received external beam radiotherapy for bone pain.
Safety evaluation All safety analyses were performed on the Safety population (708 subjects) which included all subjects who completed screening and received at least one dose of radium-223 dichloride by the end of study. Of the 708 subjects, half presented with a baseline ECOG PS of Grade 1 (49.9%), more than one third presented with a baseline ECOG PS Grade of 0 (37.4%). The remaining subjects presented with a baseline ECOG PS Grade of 2 (12.6%) and one subject had a baseline ECOG PS Grade of 4 (0.1%).
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The overall safety profile for radium-223 dichloride-treated subjects at the end of the study
was consistent to that observed at the time of primary completion.
At the end of the study, the median duration of exposure to treatment with radium-223 dichloride was 20.1 weeks. The median number of injections of study treatment was 6 injections. The median actual dose of radium-223 dichloride during the study was 293.6 kBq/kg resulting from the sum of doses actually administered in kBq at each cycle of study treatment: (radioactivity in syringe before injection - radioactivity in syringe after injection) /body weight in kg.
At primary completion, the median duration of exposure to treatment with radium-223 dichloride was 20.1 weeks. The median number of injections of study treatment was 6 injections. The median actual dose of radium-223 dichloride during the study was 293.6 kBq/kg resulting from the sum of doses actually administered in kBq at each cycle of study treatment: (radioactivity in syringe before injection - radioactivity in syringe after injection) / body weight in kg.
At the end of the study, overall, 32.9% of subjects experienced ≥1 Grade 3 treatmentemergent adverse event (TEAE) and 4.5% experienced ≥1 Grade 4 TEAE during the Treatment Period. TEAEs by preferred term during the Treatment Period reported by 5% of subjects were: anemia (20.6% overall; 10.5% Grade 3; 0.0% Grade 4), bone pain (16.0% overall; 4.1% Grade 3; 0.0% Grade 4), nausea (12.9% overall; 0.3% Grade 3; 0.0% Grade 4), diarrhea (11.3% overall; 0.6% Grade 3; 0.0% Grade 4), fatigue (9.5% overall; 1.8% Grade 3; 0.0% Grade 4), decreased appetite (7.1% overall; 0.4% Grade 3; 0.0% Grade 4), back pain (7.2% overall; 2.8% Grade 3; 0.0% Grade 4), weight decreased (7.1% overall; 0.8% Grade 3; 0.0% Grade 4), and vomiting (5.9% overall; 1.1% Grade 3; 0.0% Grade 4). TEAEs considered by the investigator to be related to radium-223 dichloride were reported by 41.0% of subjects, the most common of which were anemia (10.0%), diarrhea (8.9%), and nausea (8.8%).
At primary completion, overall, 33.3% of subjects experienced ≥1 Grade 3 TEAE and 4.5% experienced ≥1 Grade 4 TEAE during the Treatment Period. TEAEs by preferred term during the Treatment Period reported 3; 0.0% Grade 4), bone pain (15.5% overall; 4.2% Grade 3; 0.0% Grade 4), nausea (13.1% overall; 0.3% Grade 3; 0.0% Grade 4), diarrhea (11.4% overall; 0.6% Grade 3; 0.0% Grade 4), fatigue (9.6% overall; 1.9% Grade 3; 0.0% Grade 4), decreased appetite (7.2% overall; 0.4% Grade 3; 0.0% Grade 4), back pain (7.2% overall; 2.9% Grade 3; 0.0% Grade 4), weight decreased (7.0% overall; 0.7% Grade 3; 0.0% Grade 4), and vomiting (6.0% overall; 1.1% Grade 3; 0.0% Grade 4). TEAEs considered by the investigator to be related to radium-223 dichloride were reported by 40.4% of subjects, the most common of which were anemia (9.3%), diarrhea (8.9%), and nausea (8.9%).
Treatment-related hematological AEs (in the SOCs “Blood and lymphatic system disorders” and “Investigations”) were: anemia in 71 subjects (10.0%), hemoglobin decreased in 3 subjects (0.4%), neutropenia in 9 subjects (1.3%), neutrophil count decreased in 8 subjects (1.1%), thrombocytopenia in 20 subjects (2.8%), and platelet count decreased in 21 subjects (3.0%).
At primary completion, hematological adverse events during the Treatment Period (events coded under the SOCs “Blood and lymphatic system disorders” and “Investigations”) included: anemia (20.1%), hemoglobin decreased (1.7%), neutropenia (1.9%), neutrophil count decreased (1.4%), thrombocytopenia (4.2%), and platelet count decreased (3.2%).
Treatment-related hematological AEs (in the SOCs “Blood and lymphatic system disorders” and “Investigations”) were: anemia in 65 subjects (9.3%), hemoglobin decreased in 3 subjects (0.4%),
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neutropenia in 8 subjects (1.1%), neutrophil count decreased in 8 subjects (1.1%), thrombocytopenia in 20 subjects (2.9%), and platelet count decreased in 17 subjects (2.4%).
At the end of the study, TEAEs Grades 3 to 5 occurring in more than 10 subjects by preferred term were: anemia in 74 subjects (10.5%, all Grade 3), bone pain in 29 subjects (4.1%, all Grade 3), general physical health deterioration in 26 subjects (3.7% overall; 1.6% Grade 3; 0.4% Grade 4; 1.7% Grade 5), back pain in 20 subjects (2.8%, all Grade 3), spinal cord compression in 19 subjects (2.7% overall; 2.5% Grade 3; 0.1% Grade 4; 0.0% Grade 5), thrombocytopenia in 17 subjects (2.4% overall; 1.7% Grade 3; 0.7% Grade 4; 0.0% Grade 5), and fatigue in 13 subjects (1.8%, all Grade 3).
At primary completion, TEAEs Grades 3 to 5 occurring in more than 10 subjects by preferred term were: Bone pain in 29 subjects (4.2%, all Grade 3), general physical health deterioration in 26 subjects (3.7% overall; 1.6% Grade 3; 0.4% Grade 4; 1.7% Grade 5), back pain in 20 subjects (2.9%, all Grade 3), spinal cord compression in 19 subjects (2.7% overall; 2.6% Grade 3; 0.1% Grade 4; 0.0% Grade 5), thrombocytopenia in 17 subjects (2.4% overall; 1.7% Grade 3; 0.7% Grade 4; 0.0% Grade 5), and fatigue in 13 subjects (1.9%, all Grade 3).
At the end of the study, adverse events of interest reported by 5 or more subjects were: anemia in 30 subjects (4.2%), vomiting in 5 subjects (0.7%), thrombocytopenia in 11 subjects (1.6%), neutropenia in 6 subjects (0.8%), and neutrophil count decreased in 5 subjects (0.7%).
At primary completion, adverse events of interest reported by 5 or more subjects were:
anemia in 30 subjects (4.3%), vomiting in 5 subjects (0.7%), thrombocytopenia in 11 subjects (1.6%), neutropenia in 5 subjects (0.7%), and neutrophil count decreased in 5 subjects (0.7%).
At the end of the study, adverse events of hemorrhagic nature that occurred during the Treatment Period occurred in 11 subjects (1.6%); these were: eye hemorrhage (1 subject [0.1%], Grade 1), gastric hemorrhage (1 subject [0.1%], Grade 3), lower gastrointestinal hemorrhage (2 subjects [0.3%], both Grade 3), rectal hemorrhage (2 subjects [0.3%], both Grade 2), subdural hemorrhage (1 subject [0.1%], Grade 3), subarachnoid hemorrhage (1 subject [0.1%], Grade 3), penile hemorrhage (1 subject [0.1%], Grade 1), epistaxis (1 subject [0.1%], Grade 1), and subdural hematoma (1 subject [0.1%], Grade 3). None of these events had a fatal outcome.
Two were considered as related to radium-223 dichloride: subdural hemorrhage, and subarachnoid hemorrhage) led to study drug discontinuation.
At primary completion, adverse events of hemorrhagic nature that occurred during the Treatment Period occurred in 10 subjects (1.4%); these were: eye hemorrhage (1 subject [0.1%], Grade 1), gastric hemorrhage (1 subject [0.1%], Grade 3), lower gastrointestinal hemorrhage (2 subjects [0.3%], both Grade 3), rectal hemorrhage (2 subjects [0.3%], both Grade 2), subdural hemorrhage (1 subject [0.1%], Grade 3), subarachnoid hemorrhage (1 subject [0.1%], Grade 3), penile hemorrhage (1 subject [0.1%], Grade 1), epistaxis (1 subject [0.1%], Grade 1), and subdural hematoma (1 subject [0.1%], Grade 3). None of these events had a fatal outcome. Two were considered as related to radium-223 dichloride:
gastrointestinal hemorrhage and epistaxis. Three of these events (gastric hemorrhage, subdural hemorrhage, and subarachnoid hemorrhage) led to study drug discontinuation.
At the end of study, overall, 246 (34.7%) subjects experienced a treatment-emergent SAE during the Treatment Period (21.0% Grade 3; 4.0% Grade 4; 4.9% Grade 5). Treatmentemergent SAEs by preferred term during the Treatment Period reported by >5 subjects were:
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anemia (3.2% overall; 2.5% Grade 3; 0.0% Grade 4; 0.0% Grade 5), pneumonia (1.3% overall; 1.0% Grade 3; 0.0% Grade 4; 0.1% Grade 5), sepsis (0.8% overall; 0.0% Grade 3; 0.4% Grade 4; 0.4% Grade 5), urosepsis (0.8% overall; 0.1% Grade 3; 0.6% Grade 4; 0.1% Grade 5), back pain (2.3% overall; 2.0% Grade 3; 0.0% Grade 4; 0.0% Grade 5), bone pain (1.7% overall; 1.4% Grade 3; 0.0% Grade 4; 0.0% Grade 5), spinal cord compression (2.7% overall; 2.3% Grade 3; 0.1% Grade 4; 0.0% Grade 5), hematuria (1.3% overall; 1.1% Grade 3; 0.0% Grade 4; 0.0% Grade 5), and hydronephrosis (1.0% overall; 1.0% Grade 3; 0.0% Grade 4; 0.0% Grade 5). The most common treatment-emergent gastrointestinal SAE reported in more than 5 subjects was vomiting (1.0% overall; 1.0% Grade 3; 0.0% Grade 4; 0.0% Grade 5).
At primary completion, overall, 243 (34.9%) subjects experienced a treatment-emergent SAE during the Treatment Period (21.4% Grade 3; 3.9% Grade 4; 4.9% Grade 5). Treatmentemergent SAEs by preferred term during the Treatment Period reported by >5 subjects were:
anemia (3.3% overall; 2.6% Grade 3; 0% Grade 4; 0% Grade 5), pneumonia (1.3% overall; 1.0% Grade 3; 0% Grade 4; 0.1% Grade 5), sepsis (0.9% overall; 0% Grade 3; 0.4% Grade 4; 0.4% Grade 5), urosepsis (0.9% overall; 0.1% Grade 3; 0.6% Grade 4; 0.1% Grade 5), back pain (2.3% overall; 2.0% Grade 3; 0% Grade 4; 0% Grade 5), bone pain (1.6% overall; 1.4% Grade 3; 0% Grade 4; 0% Grade 5), spinal cord compression (2.7% overall; 2.3% Grade 3; 0.1% Grade 4; 0% Grade 5), hematuria (1.3% overall; 1.1% Grade 3; 0% Grade 4; 0% Grade 5), and hydronephrosis (1.0% overall; 1.0% Grade 3; 0% Grade 4; 0% Grade 5). The most common treatment-emergent gastrointestinal SAE reported in more than 5 subjects was vomiting (1.0% overall; 1.0% Grade 3; 0% Grade 4; 0% Grade 5).
At the end of the study, additional primary malignancies during the Treatment Period were reported in 11 subjects in addition to the 9 subjects (1.3%) with reported events at primary completion: oral cavity cancer (diagnosed shortly after fourth [final] dose of study drug [exact date unknown]), squamous cell cancer (diagnosed on the day of sixth [final] dose of study drug), pseudomyxoma peritonei (diagnosed 71 days after sixth [final] dose of study drug), bladder cancer (diagnosed 26 days after fifth [final] dose of study drug), soft tissue carcinoma (diagnosed 32 days after fourth dose of study drug; subject completed 6 cycles of treatment), kidney cancer (diagnosed 12 days after first dose of study drug; subject completed 6 cycles of treatment), basal cell carcinoma (diagnosed on day of fourth dose of study drug; subject received final dose at cycle 5), primary bone cancer (diagnosed on day of fifth dose of study drug; subject completed 6 cycles of treatment), and malignant melanoma (diagnosed 13 days after fifth dose of study drug; subject completed 6 cycles of treatment). All events occurred in 1 subject each (0.1%). None of these malignancies were considered related to study drug.
At the end of the study, treatment-emergent AEs leading to discontinuation during the Treatment Period were reported in 147 subjects (20.8%); those that occurred in 1% of subjects were: anemia (2.3%), thrombocytopenia (1.6%), general physical health deterioration (3.0%), and platelet count decreased (1.4%). Gastrointestinal disorders that led to study drug discontinuation occurred in 8 subjects (1.1% overall; 0.1% Grade 1; 0.3% Grade 2; 0.6% Grade 3; 0.1% Grade 4).
At primary completion, treatment-emergent AEs leading to discontinuation during the Treatment Period were reported in 144 subjects (20.7%); those that occurred in 1% of subjects were: anemia (2.2%), thrombocytopenia (1.6%), general physical health deterioration (3.0%), and platelet count decreased (1.3%). Gastrointestinal disorders that led to study drug discontinuation occurred in 8 subjects (1.1% overall; 0.1% Grade 1; 0.3% Grade 2; 0.6% Grade 3; 0.1% Grade 4).
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By the end of the study, a total of 224 (31.6%) subjects had died. At primary completion, a total of 210 (30.2%) subjects had died during the study. However, the follow-up period of the current study was short.
During the Treatment Period, most subjects had no change in the CTCAE severity Grade for chemistry parameters. The same was observed during the Follow-up Period, when most subjects had no change in the CTCAE severity Grade for chemistry parameters. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) median values showed small changes over time but the changes observed were not clinically meaningful. Bilirubin and sodium, showed minimal to no change among median values.
During the Treatment Period, in the majority of subjects, anemia, white blood cell decreased, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased remained stable throughout the study with no worsening, confirming the good hematological toxicity profile of radium-223 dichloride. For lymphocyte count increased, showed small changes over time but the changes observed were not clinically meaningful.
With regard to BPI-SF scores, both at primary completion and at the end of the study, there was a nominal decrease in mean worst pain in the past 24 hours observed at every scheduled post-baseline assessment (range, -0.2 to -0.5); mean pain severity score decreased from baseline at every scheduled post-baseline assessment (range, -0.03 to -0.33); mean pain interference score decreased at every scheduled post-baseline on-treatment assessment (range, -0.10 to -0.28).
Overall conclusions In conclusion, the safety results at the end of this study confirm the favorable tolerability and safety profile of radium-223 dichloride. Median overall survival in the current study was 16 months.
Appendix to Clinical Study Synopsis
Page 1 of 12
Investigational Site List
Marketing Authorization Holder in Germany
Name Bayer Vital GmbH
Postal Address D-51368 Leverkusen
Germany
Sponsor in Germany (if applicable)
Legal Entity Name Bayer AG
Postal Address
D-51368 Leverkusen Germany
List of Investigational Sites
No Investigator Name
Facility Name Street ZIP Code
City Country
1 Prof. Dr.Michael Krainer
Allgemeines Krankenhaus der Stadt Wien
Währinger Gürtel 18-20 1090 Wien Austria
2 Prof. Dr.Irene Virgolini
Landeskrankenhaus - Universitätskliniken Innsbruck
Anichstraße 35 6020 Innsbruck Austria
3 Prof. Dr.Christian Pirich
Landeskrankenhaus Salzburg - Universitätsklinikum der PMU
Müllner Hauptstrasse 48 5020 Salzburg Austria
4 Prof. Dr.Francois JAMAR
CU Saint-Luc/UZ St-Luc Avenue Hippocrate 10 Hippocrateslaan
1200 BRUXELLES - BRUSSEL
Belgium
5 Dr.Thierry GIL Institut Jules Bordet/Jules Bordet Instituut
Boulevard de Waterloo 121
1000 BRUXELLES - BRUSSEL
Belgium
6 Dr.Nicolaas LUMEN UZ Gent De Pintelaan 185 9000 GENT Belgium
7 Dr.Nicolas WHENHAM
Clinique Saint-Pierre Avenue Reine Fabiola 9 1340 OTTIGNIES Belgium
8 Dr.Alain BOLS AZ St-Jan Brugge Oostende AV
Site St Jan A. Ruddershove 10
8000 BRUGGE Belgium
9 Dr.Ignace BILLIET AZ Groeninge Campus Vercruysselaan
Burgemeester Vercruysselaan 5
8500 KORTRIJK Belgium
10 Dr.Christophe DEROOSE
UZ Leuven Gasthuisberg Herestraat 49 3000 LEUVEN Belgium
11 Dr.Jan VAN DEN BRANDE
UZ Antwerpen Wilrijkstraat 10 2650 EDEGEM Belgium
12 Dr.Denis SCHALLIER UZ Brussel Laarbeeklaan 101 1090 BRUXELLES - BRUSSEL
Belgium
13 Dr.Derek Wilke Queen Elizabeth II Health Sciences Centre
Nova Scotia Cancer Center 5820 University Avenue Dickson Bldg. Rm 2027
B3H 2V7 Halifax Canada
14 Dr.Catherine Sperlich Hopital Charles LeMoyne CISSS de la Montérégie-Centre 3120 Boulevard Taschereau
J4V 2H1 Greenfield Park
Canada
15 Dr.Samir Patel Cross Cancer Institute 11560 University Avenue T6G 1Z2 Edmonton Canada
16 Dr.Anthony Joshua Princess Margaret Hospital-University Health Network
Department of Medical Oncology 610 University Avenue
M5G 2M9 Toronto Canada
17 Dr.Scott Tyldesley British Columbia Cancer Agency-Vancouver Centre
Radiation Oncology 600 West 10th Avenue Room 4552 Radiation Oncology Department
V5Z 4E6 Vancouver Canada
Appendix to Clinical Study Synopsis
Page 2 of 12
18 Dr.Scott Berry Sunnybrook Health Sciences Centre
Odette Cancer Centre 2075 Bayview Avenue T Wing
M4N 3M5 Toronto Canada
19 Dr.Shaun Malone Ottawa Hospital-General Campus
501 Smyth Road K1H 8L6 Ottawa Canada
20 Dr.Fred Saad CHUM - Hopital Notre-Dame 1560 Sherbrooke east Pavillon Mailloux /Room K-5224
H2L 4M1 Montreal Canada
21 M. Dr. med.Dominik Berthold
Centre Hospitalier Universitaire Vaudois (CHUV)
17, Rue de Bugnon 1011 Lausanne Switzerland
22 Frau Prof. Dr.Silke Gillessen
Kantonsspital St. Gallen Rorschacher Str. 95 9007 St. Gallen Switzerland
23 Hr. Dr. med.Richard Cathomas
Kantonsspital Graubünden Loëstrasse 170 7000 Chur Switzerland
24 Hr. Dr. med.Christoph Mamot
Kantonsspital Aarau Buchser Straße 5001 Aarau Switzerland
25 Hr. Dr. med.Sacha Rothschild
Universitätsspital Basel Spitalstrasse 21 / Petersgraben 4
4056 Basel Switzerland
26 S. Dr. med.Enrico Roggero
Ospedale Regionale Bellinzona Istituto Oncologico della Svizzera Italiana
6500 Bellinzona Switzerland
27 Hr. Prof. Dr.Thomas Krause
Inselspital Universitätsspital Bern
Freiburger Str. 4 3010 Bern Switzerland
28 Hr. Dr. med.Niklaus Schäfer
Universitätsspital Zürich Rämistraße 100 8091 Zürich Switzerland
29 Mme.Marie-Laure Amram
Hôpital Cantonal Universitaire de Genève
Service d'Oncologie Département de Médecine Interne Rue Gabrielle-Perret-Gentil 4
Switzerland
30 Prof.Jitka Abrahamova
Fakultni Thomayerova Nemocnice
Videnska 800 140 59 Praha 4 Czech Republic
31 DrDavid Feltl Fakultni nemocnice Ostrava Oncology clinic 17 listopadu 1790
708 52 Ostrava Czech Republic
32 Prof.Marek Babjuk Fakultni nemocnice v Motole V Uvalu 84 150 06 Praha 5 Czech Republic
33 Prof.Milan Hora Fakultni nemocnice Plzen Dr. Edvarda Benese 13 305 99 Plzen - Bory Czech Republic
34 DrJana Katolicka Fakultni nemocnice u sv. Anny Pekarska 53 656 91 Brno Czech Republic
35 Hr. Prof. Dr.Kurt Miller
Charité Campus Benjamin Franklin (CBF)
Klinik und Poliklinik für Urologie des Universitätsklinikums Benjamin Franklin Hindenburgdamm 30
12200 Berlin Germany
36 Hr. Prof. Dr.Manfred Wirth
Medizinische Fakultät Carl Gustav Carus
Technische Universität Dresden Klinik und Poliklinik für Urologie Fetscherstraße 74
01307 Dresden Germany
37 Hr. Prof. Dr.Axel Heidenreich
Universitätsklinikum Aachen Urologische Klinik Pauwelsstraße 30
52074 Aachen Germany
38 Hr. Prof. Dr.Peter Hammerer
Städtisches Klinikum Braunschweig gGmbH
Urologische Klinik Salzdahlumer Str. 90
38118 Braunschweig Germany
39 Hr. Prof. Dr.Markus Kuczyk
Medizinische Hochschule Hannover (MHH)
Klinik für Urologie Carl-Neuberg-Str. 1
30625 Hannover Germany
40 Hr. PD Dr.Georg Bartsch
Universitätsklinikum der Johann Wolfgang Goethe Universität
Klinik für Urologie und Kinderurologie Theodor-Stern-Kai 1
60590 Frankfurt Germany
41 Hr. Dr.Michael Staehler
Klinikum der Universität München Grosshadern
Urologische Klinik und Poliklinik Marchioninistr. 15
81377 München Germany
42 Hr. Dr.Arne Strauss Universitätsmedizin der Georg-August-Universität Göttingen
Urologie Robert-Koch-Strasse 40
37075 Göttingen Germany
Appendix to Clinical Study Synopsis
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43 Hr. Dr.Boris Hadaschik
Universitätsklinikum Heidelberg
Urologische Universitätsklinik Im Neuenheimer Feld 110
69112 Heidelberg Germany
44 Fr. PD Dr.Margitta Retz
Klinikum rechts der Isar Urologische Klinik und Poliklinik Ismaninger Straße 22
81675 München Germany
45 Hr. PD Dr.Christian Hampel
Universitätsmedizin der Johannes Gutenberg Universität Mainz
Urologische Klinik und Poliklinik Langenbeckstr. 1
55131 Mainz Germany
46 Hr. Dr.Martin Burmester
Vinzenzkrankenhaus Hannover gGmbH
Lange-Feld-Straße 31 30559 Hannover Germany
47 Hr. Dr.Andreas Hübner
Zentrum für Onkologie und Urologie Rostock
Trelleborger Str. 10 a 18107 Rostock Germany
48 Hr. PD Dr.Frank König
Urologische Gemeinschaftspraxis
Aturoberlin Mecklenburgische Str. 27
14197 Berlin Germany
49 Hr. Dr. med.Wolfgang von Pokrzywnitzki
Vivantes Klinikum Am Urban Klinik für Urologie Dieffenbachstr. 1
10967 Berlin Germany
50 Hr. Prof. Dr.Gerald Mickisch
Urologische Gemeinschaftspraxis
Robert-Koch-Str. 34 a 28277 Bremen Germany
51 Hr. PD Dr.Peter Goebell
Universitätsklinikum Erlangen Standort Waldkrankenhaus St. Marien Urologische Klinik Rathsbergerstr. 57
91054 Erlangen Germany
52 Hr. Prof. DrMartin Schostak
Medizinische Fakultät der Otto-von-Guericke Universität
Klinik für Urologie und Kinderurologie Leipziger Straße 44
39120 Magdeburg Germany
53 Hr. Prof. Dr.Arnulf Stenzl
Klinikum der Eberhard-Karls-Universität Tübingen
Universitätsklinik für Urologie Hoppe-Seyler-Str. 3
72076 Tübingen Germany
54 Hr. PD Dr.Marc-Oliver Grimm
Klinikum der Friedrich-Schiller-Universität Jena
Klinik und Poliklinik für Urologie Lessingstr. 1
07740 Jena Germany
55 Hr. Dr.Christian Arsov
Medizinische Einrichtungen der Heinrich-Heine-Universität
Urologische Klinik Moorenstr. 5
40225 Düsseldorf Germany
56 Hr.Oliver Hakenberg Universität Rostock - Medizinische Fakultät
Klinik und Poliklinik für Innere Medizin Abteilung Hämatologie und Onkologie Ernst-Heydemann-Str. 6
18057 Rostock Germany
57 Hr. Dr.Friedrich Overkamp
Oncologianova GmbH Springstraße 24 45657 Recklinghausen
Germany
58 Hr. PD Dr.Carsten Ohlmann
Universitätsklinikum des Saarlandes
Klinik für Urologie und Kinderurologie Kirrberger Str. 1
66421 Homburg Germany
59 Hr. Dr.Götz Geiges Praxis Hr. Dr. G. Geiges Lietzenburger Str. 54 10719 Berlin Germany
60 Hr. Dr.Peter Olbert Universitätsklinik Gießen und Marburg GmbH
Klinik für Urologie und Kinderurologie Baldingerstr.
35043 Marburg Germany
61 Hr. Dr.Norbert Marschner
Praxis für interdisziplinäre Onkologie und Hämatologie
Breisacher Str. 117 79106 Freiburg im Breisgrau
Germany
62 Hr. Dr.Sebastian Rogenhofer
Medizinische Einrichtungen der Universität Bonn
Klinik und Poliklinik für Urologie Sigmund-Freud-Straße 25
53105 Bonn Germany
63 Hr. Dr.Ilija Damjanoski
Universitätsklinikum Ulm Urologische Universitätsklinik und Poliklinik Prittwitzstrasse 43
89075 Ulm Germany
64 Hr. Prof. Dr.Hans Heinzer
Universitätsklinikum Hamburg Eppendorf (UKE)
Klinik und Poliklinik für Urologie Martinistr. 52
20246 Hamburg Germany
65 Hr Dr.Martin Bögemann
Universitätsklinikum Münster (UKM)
Abteilung Urologie Gebäude A1 Albert-Schweitzer-Campus
48149 Münster Germany
Appendix to Clinical Study Synopsis
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1
66 Hr. Dr.Ulrich Kube Urologische Gemeinschaftspraxis
Goethestr. 5 A 09119 Chemnitz Germany
67 Fr. Dr.Laura Hoppe Klinikum der Ernst-Moritz-Arndt-Universität
Klinik und Poliklinik für Urologie Ferdinand-Sauerbruch-Str.
17475 Greifswald Germany
68 Hr. Dr.Andreas Zinke Klinikum der Ernst-Moritz-Arndt-Universität
Universitätsmedizin Greifswald Klinik und Poliklinik für Nuklearmedizin Fleischmannstraße 42 - 44
17475 Greifswald Germany
69 MDHenriette Lindberg
Herlev Hospital Onkologisk afd R Herlev ringvej 75
2730 Herlev Denmark
70 MDPeter Petersen H:S Rigshospitalet Onkologisk klinik 5073 Blegdamsvej 9
2100 København Denmark
71 MD, PhDSteinbjoern Hansen
Odense Universitetshospital Odense Universitetshospital Onkologisk afd Sdr. Boulevard 29
5000 Odense Denmark
72 Dr.Joan Carles Galcerán
Ciutat Sanitària i Universitaria de la Vall d'Hebron
Servicio de Oncología Médica Passeig de la Vall d'Hebrón, 119-129 Edificio General, 2ª Planta
08035 Barcelona Spain
73 Dr.José Luis Pérez Gracia
Clínica Universidad de Navarra CUN
Servicio de Oncología Avda. Pio XII, 36
31008 Pamplona Spain
74 Dra.Cristina Caballero Díaz
Hospital General Universitario de Valencia
Servicio de Oncología Avda Tres Cruces, s/n
46014 Valencia Spain
75 Dra.Pilar López Criado
MD Anderson International Espanya, S.A.
Consultant of Medical Oncology Arturo Soria, 270
28033 Madrid Spain
76 Dra.María López Hospital Ramón y Cajal Servicio de Oncología Ctra. de Colmenar, Km. 9,1
28034 Madrid Spain
77 Dr.Urbano Anido Herranz
Hospital Clínico Universitario de Santiago de Compostela
Servicio de Oncología A Choupana, s/n
15706 Santiago de Compostela
Spain
78 Dr.José Manuel Trigo Pérez
Hospital Virgen de la Victoria Servicio de Oncologia Medica, Planta 1 Campus Teatinos, s/n
29010 Malaga Spain
79 Dr.José Angel Arranz Arija
Hospital General Universitario Gregorio Marañón
Servicio de Oncologia Medica, Planta 2 C/ Dr Esquerdo, 46
28007 Madrid Spain
80 Dra.Susana Hernando Polo
Fundación Hospital Alcorcón Hospital de día médico. Servico de Oncología c/ Budapest, 1
28922 Spain
81 Dr.José Maroto Rey Hospital de la Santa Creu i de Sant Pau
Servicio de Oncología C/Mas Casanovas, 90
08025 Barcelona Spain
82 Dra.Begona Mellado González
Hospital Clínic i Provincial de Barcelona
Servicio de Oncología Médica C/ Villarroel, 170
08036 Barcelona Spain
83 Dra.Aránzazu González del Alba
Hospital Universitari Son Espases
Servicio de Oncología Ctra. Valldemossa, 79
Palma de Mallorca
Spain
84 Dr.Álvaro Pinto Hospital Universitario "La Paz" Hospital de Día de Oncología Paseo de la Castellana, 261
28046 Madrid Spain
85 Dra.Ma José Méndez Vidal
Hospital Reina Sofía Servicio de oncología Avda. Menéndez Pidal, s/n
14004 Córdoba Spain
86 Dra.Nuria Laínez Hospital de Navarra Servicio de Oncología Avda. Irunlarrea, 3
31008 Pamplona Spain
87 Dr.José Luis González-Larriba
Hospital Clínico Universitario San Carlos
Servicio de Oncología Médica. Pabellón B. Planta Baja C/. Dr. Martín Lagos, s/n
28040 Madrid Spain
88 Dr.Josep Piulats Institut Català d'Oncologia Servicio de Oncologia 08907 Hospitalet de Spain
Appendix to Clinical Study Synopsis
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Medica Avda.Gran Via, s/n, Km 2,7
Llobregat
89 Dr.Sergio Vázquez Hopsital Lucus Agustí Servicio de Oncología c/ San Cibrao s/n
27004 Lugo Spain
90 Dr.Ángel Rodríguez Hospital de León Servicio de Oncología Altos de Nava, s/n
24008 León Spain
91 Dr.Luis Miguel Antón Aparicio
Hospital Teresa Herrera Servicio de Oncología Carretera del Pasaje
15006 A Coruña Spain
92 Dr.Miguel Angel Climent
Instituto Valenciano de Oncología
Servicio de Oncología Médica Despacho de Ensayos Clínicos c/ Gregorio Gea, 31, 1ª Planta
46009 Valencia Spain
93 Dr.Alberto Saenz-Cusí
Hospital Clínico Universitario Lozano Blesa
Servicio de Oncologia Medica C/ San Juan Bosco, 15
50009 Zaragoza Spain
94 Dra.Marta López Brea Hospital Universitario "Marqués de Valdecilla"
Servicio de Oncología Avda. de Valdecilla, 25
39008 Santander Spain
95 Dr.Daniel Castellano Guana
Hospital Universitario 12 de Octubre
Servicio Oncología Médica Av. de Córdoba, s/n
28041 Madrid Spain
96 Dr.Salvador Saura Hospital Dr. Negrín Barranco de la Ballena, s/n
35020 Las Palmas de Gran Canaria
Spain
97 Dr.Rocío García Domínguez
Hospital Clínico de Salamanca Paseo San Vicente, 182 37007 Salamanca Spain
98 Dr.Álvaro Montesa Hospital Regional Carlos Haya Servicio de Oncología Médica Avda. Carlos Haya s/n
29010 Málaga Spain
99 Dra.Begona Pérez Valderrama
Hospital Universitario Virgen del Rocío
Servicio de Oncología Av. Manuel Siurot, s/n
41013 Sevilla Spain
100 Dr.Miguel Ángel Cabrera
Hospital de Nuestra Señora de la Candelaria
Ctra. del Rosario, 145 38009 Santa Cruz de Tenerife
Spain
101 Dr.Juan Virizuela Echaburu
Hospital Universitario Virgen de la Macarena
Servicio de Oncología Avda. Dr. Fedriani, s/n
41071 Sevilla Spain
102 Dr.Roberto Llarena Hospital de Cruces Servicio de Oncología Pza. de Cruces, s/n
48903 Cruces/Barakaldo
Spain
103 Dr.Emilio Esteban Hospital Central de Asturias Servicio de Oncología Médica Celestino Villamil, s/n
33006 Oviedo Spain
104 Dr.Gaspar Reynes Hospital Universitari i Politècnic La Fe
Servicio de Oncología Médica Avenida de Fernando Abril Martorell, 106
46026 Valencia Spain
105 DrTimo Joensuu Docrates Klinikka Saukonpaadenranta 2 00180 Helsinki Finland
106 Dr.Petteri Hervonen Tampereen yliopistollinen sairaala, keskussairaala
Teiskontie 35 FIN-33520
Tampere Finland
107 Dr.Tapio Utriainen HUS, Meilahden sairaala Department of Oncology Haartmaninkatu 4 Helsinki
00029 HUS Finland
108 Dr.Timo Marttila Seinäjoen keskussairaala A32 Hanneksenrinne 7
60220 Seinäjoki Finland
109 DrKalevi Pulkkanen Kuopion yliopistollinen sairaala Syöpäkeskus Puijonlaaksontie 2
70211 Kuopio Finland
110 DrMarjaana Luukkaa Turun yliopistollinen keskussairaala, kantasairaala
Oncological Department (T hospital) P.O.Box 52 Hämeentie 11
FIN-20521
Turku Finland
111 Pr.Stéphane OUDARD
Hopital Européen Georges Pompidou - Paris
Hopital Européen Georges Pompidou Service de Cardiologie 1 Ascenseur A - 3ème étage 20-40 rue Leblanc
75908 PARIS CEDEX 15
France
Appendix to Clinical Study Synopsis
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112 DocteurDavid AZRIA Institut du Cancer de Montpellier
ICM - Centre Val d'Aurelle 208 rue des Apothicaires
34298 MONTPELLIER CEDEX
France
113 DrNicolas PENEL Centre Oscar Lambret - Lille Centre Oscar Lambret 3, rue Frédéric Combemale
59020 LILLE CEDEX France
114 DrFlorence JOLY Centre François Baclesse - CLCC - Caen
Centre François Baclesse Centre de Lutte Contre le Cancer Route de Lion sur Mer B.P. 5026
14076 CAEN CEDEX 5
France
115 DrCaroline ROUSSEAU
Centre René Gauducheau - Nantes
Centre René Gauducheau Boulevard Jacques Monot
44805 SAINT HERBLAIN
France
116 DrHakim MAHAMMEDI
Centre Jean Perrin 58, rue Montalembert B.P. 392
63011 CLERMONT FERRAND CEDEX 1
France
117 PrStéphane CULINE Hôpital Saint Louis - Paris Hôpital Saint Louis 1, avenue Claude Vellefaux
75010 PARIS France
118 DrSophie LEBOULLEUX
Institut Gustave Roussy - Villejuif
Institut Gustave Roussy 114 rue Edouard Vaillant
94805 VILLEJUIF CEDEX
France
119 PrThierry LEBRET Centre Médico-Chirurgical Foch
40, rue Worth 92151 SURESNES France
120 ProfesseurMarc ZERBIB
Cochin - Paris Hôpital Cochin 27, rue du Faubourg Saint-Jacques
75674 PARIS France
121 PrJean-Marc TOURANI
Centre Hospitalier Universitaire - Poitiers
Centre Hospitalier Universitaire Rue de la Milétrie
86021 POITIERS CEDEX
France
122 PrJean Philippe VUILLEZ
Centre Hospitalier Universite de Grenoble
Centre Hospitalier Universitaire de Grenoble BP 217 38043 Grenoble
38043 Grenoble France
123 DrXavier REBILLARD Clinique Beausoleil - Montpellier
Clinique Beausoleil 119 avenue Lodève
34070 MONTPELLIER
France
124 DrAbdel AZZOUZI Centre Hospitalier Universitaire - Angers
Centre Hospitalier Universitaire 4, rue Larrey
49033 ANGERS CEDEX 01
France
125 DrIvan krakowski Centre Alexis Vautrin 6 Avenue de Bourgogne 54500 Vandoeuvre les Nancy
France
126 ProfesseurArnauld VILLERS
Hôpital Claude Huriez - Lille C.H.R.U. Rue Michel Polonovsky
59037 LILLE France
127 DrFrank PRIOU Centre Hospitalier Départemental-La Roche sur Yon
Les Oudairies 85025 LA ROCHE SUR YON CEDEX
France
128 DocteurJean-Louis DAVIN
Clinique Rhone Durance - Avignon
Clinique Rhone Durance 1750 chemin Lavarin
84000 AVIGNON France
129 PrMichel SOULIE Hôpital de Rangueil - Toulouse C.H.U. Hôpital de Rangueil 1, avenue du Pr Jean Poulhes
31059 TOULOUSE cedex
France
130 DrChristopher Parker Royal Marsden NHS Trust (Surrey)
Downs Road SM2 5PT Sutton United Kingdom
131 DrOmar Din Weston Park Hospital Sheffield Teaching Hospitals NHS Foundation Trust Department of Oncology, Cancer Clinical Trials Centre Academic Unit of Clinical Oncology Broomcross Building Weston Park Hospital, Whitham Road
S10 2SJ Sheffield United Kingdom
132 DrDanish Mazhar Addenbrookes Hospital Hills Road CB2 0QQ Cambridge United Kingdom
133 DrDavid Bottomley St James' University Hospital Bexley Wing St James's Hospital
LS9 7TF Leeds United Kingdom
Appendix to Clinical Study Synopsis
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Beckett Street
134 DrPrabir Chakraborti Royal Derby Hospital Derby Teaching Hospitals NHS Foundation
Royal Derby Hospital Derby Teaching Hospitals NHS Foundation Trust Uttoxeter Road
DE22 3NE
Derby United Kingdom
135 DrSarah Pascoe Derriford Hospital Department Of Oncology Derriford Hospital Derriford Road
PL6 8DH Plymouth United Kingdom
136 DrCatherine Heath Southampton General Hospital Oncology Department Southampton General Hospital Tremona Road
SO16 6YD
Southampton United Kingdom
137 DrJohn Graham Musgrove Park Hospital Musgrove Park Hospital Parkfield Drive
TA1 5DA Taunton United Kingdom
138 DrGraham (Alan) Macdonald
Aberdeen Royal Infirmary Foresterhill AB25 2ZN
Aberdeen United Kingdom
139 DrAzmat Sadozye Beatson West of Scotland Cancer Centre
1053 Great Western Road G12 0YN Glasgow United Kingdom
140 DrIsabel Syndikus Clatterbridge Centre for Oncology
Clatterbridge Road CH63 4JY
Bebington United Kingdom
141 DrSanjay Dixit Castle Hill Hospital Cancer Centre Castle Hill Hospital Castle Road, Cottingham
HU16 5JQ
Hull United Kingdom
142 DrJacob Tanguay Velindre Hospital Velindre Cancer Centre Velindre Road Whitchurch
CF14 2TL Cardiff United Kingdom
143 DrStephanie Gibbs Queens Hospital Rom Valley Way RM7 0AG Romford United Kingdom
144 DrSanthanam Sundar Nottingham City Hospital Department of Clinical Oncology Hucknall Road
NG5 1PB Nottingham United Kingdom
145 DrChristopher Scrase NRES Committee South West - Central Bristol
South West Reseach Ethics Committee Centre Level 3, Block B Whitefriars Lewins Mead
BS1 2NT Bristol United Kingdom
146 DrAmit Bahl Bristol Haematology & Oncology Centre
University Hospital Bristol NHS Foundation Horfield Road
BS2 8ED Bristol United Kingdom
147 DrIan Sayers New Cross Hospital Wolverhampton Road Heath Town
WV10 0QP
Wolverhampton
United Kingdom
148 DrPaul (Tony) Elliott Christie Hospital 550 Wilmslow Road Withington
M20 4BX Manchester United Kingdom
149 ProfessorJoseph (Joe) O'Sullivan
Belfast City Hospital Cancer Centre Belfast City Hospital Lisburn Road
BT9 7AB Belfast United Kingdom
150 DrAndrew Stockdale University Hospital Walsgrave site Clifford Bridge Road
CV2 2DX Coventry United Kingdom
151 DrRhona McMenemin Freeman Hospital Sir Bobby Robson Cancer Trials Research Centre Northern Centre for Cancer Care Freeman Hospital, Level 2, Freeman Road
NE7 7DN Newcastle Upon Tyne
United Kingdom
152 ProfessorNicholas James
Queen Elizabeth Hospital Queen Elizabeth Medical Centre Edgbaston
B15 2TH Birmingham United Kingdom
153 ProfessorValerie Lewington
Guy's Hospital Department of Nuclear Medicine Great Maze Pond
SE1 9RT London United Kingdom
154 ProfessorPeter Hoskins
Mount Vernon Hospital Department of Haematology & Oncology Rickmansworth Road
HA6 2VR Northwood United Kingdom
155 DrJulian Money-Kyrle Royal Surrey County Hospital St Luke's Oncology Centre GU2 7XX Guildford United
Appendix to Clinical Study Synopsis
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Egerton Road
Kingdom
156 DrDuncan McLaren Western General Hospital Crewe Road EH4 2XU Edinburgh United Kingdom
157 DrSubramaniam Vasanthan
Leicester Royal Infirmary Infirmary Square LE1 5WW
Leicester United Kingdom
158 ProfessorFrank Sullivan
University College Hospital Galway
University Hospital Galway Newcastle Road
Galway Ireland
159 DrJerome Coffey St Luke's Hospital Highfield Road Rathgar
Dublin 6 Ireland
160 DrPaul Kelly Cork University Hospital Oncology Department Cork University Hospital Wilton
Cork Ireland
161 Dr.Wilmosh Mermershtein
Soroka University Medical Center
Yitskhak Rager Av. P.O.B 151
8410101 Beer Sheva Israel
162 Dr.Daniel Kejzman Meir Medical Center Clalit Health Services 59, Tchernichovsky Street
4428164 Kfar Saba Israel
163 Dr.Avivit Peer Rambam Health Corporation 8, Haaliya Hashniya St. 3109601 Haifa Israel
164 Prof.Avishai Sella Assaf Harofeh Medical Center Assaf Harofeh Medical Center
6093000 Zerifin Israel
165 Dr.Stephen Frank Hadassah Hebrew University Hospital Ein Kerem
Kiryat Hadassah P.O.B 12000
9112001 Jerusalem Israel
166 Dr.Eli Rosenbaum Rabin Medical Center - Beilinson Campus
39 Jabotinski Street 4941492 Petah Tikva Israel
167 Dr.Eliahu Gez Tel-Aviv Sourasky Medical Center
6 Weizmann Street 6423906 Tel Aviv Israel
168 Dr.Michael Dinerman Kaplan Medical Center Pasternak St. P.O.B. 1
7610001 Rehovot Israel
169 Dr.Raanan Berger Chaim Sheba Medical Center Chaim Sheba Medical Center Tel Hashomer
5262000 Ramat Gan Israel
170 Dr.Giovanni Paganelli IRST Istituto Scientifico Romagnolo per studio e cura Tumori
Medicina Radiometabolica Direttore: Prof. Giovanni Paganelli Via P. Maroncelli, 40 - Meldola
47014 Forlì Italy
171 Dr.Giuseppe Procopio Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Oncologia Medica 2 Dip. Oncologia Medica Via G. Venezian, 1
20133 Milano Italy
172 Dr.Caterina Messina A.O. Ospedali Riuniti Bergamo Oncologia Medica Largo Barozzi, 1
24128 Bergamo Italy
173 Prof.Massimo Aglietta IRCCS Fondazione del Piemonte per l'Oncologia
Oncologia Medica Direttore: Prof. Massimo Aglietta Istituto Ricerca e Cura del Cancro di Candiolo Strada Provinciale 142 Km 3,95 - Candiolo
10060 Torino Italy
174 Prof.Alfredo Falcone A.O.U. Pisana Oncologia Medica 2 Universitaria Direttore: Prof. Alfredo Falcone Polo Oncologico di Area Vasta Nord-Ovest - Ospedale Santa Chiara Via Roma, 67
56126 Pisa Italy
175 Dr.Annibale Versari A.O. di Reggio Emilia Medicina Nucleare Direttore: Dr. Annibale Versari Arcispedale Santa Maria Nuova Viale Risorgimento, 80
42123 Reggio Emilia Italy
176 Dr.Armando Santoro IRCCS Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
Oncologia Medica ed Ematologia Direttore: Dr. Armando
20089 Milano Italy
Appendix to Clinical Study Synopsis
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Santoro Via A. Manzoni, 56 - Rozzano
177 Prof.Enrico Cortesi Azienda Policlinico Umberto I Oncologia Medica B Direttore: Prof. Enrico Cortesi Dip. Scienze Radiologiche, Oncologiche e Anatomo-Patologiche Viale del Policlinico, 155
00161 Roma Italy
178 Prof.Sergio Baldari A.O.U. Policlinico G. Martino Medicina Nucleare Dip. Diagnostica per Immagini Via Consolare Valeria
98125 Messina Italy
179 Prof.Giorgio Scagliotti A.O.U. San Luigi Gonzaga Oncologia Medica Direttore: Prof. Giorgio Scagliotti Dip. Oncologia Regione Gonzole, 10 - Orbassano
10043 Torino Italy
180 Dr.Vittorio Ferrari A.O. Spedali Civili di Brescia (ended 31Dec2015)
Oncologia Medica Direttore: Dr. Alfredo Berruti Dip. Oncologia Clinica Piazzale Spedali Civili, 1
25123 Brescia Italy
181 Dr.Manlio Cabria E.O. Ospedali Galliera Medicina Nucleare Direttore f.f. Dott. Manlio Cabria Dip. Area Diagnostica per Immagini Via A. Volta, 6 - Padiglione U
16128 Genova Italy
182 Dr.Lucia Fratino IRCCS Centro di Riferimento Oncologico - CRO
Oncologia Medica A Direttore: Prof. Umberto Tirelli Dip. Oncologia Medica Via F. Gallini, 2 - Aviano
33081 Pordenone Italy
183 Prof.Franco Silvestris A.O.U. Policlinico Consorziale Oncologia Medica Universitaria Direttore: Prof. Franco Silvestris Piazza Giulio Cesare, 11
70124 Bari Italy
184 Dr.Claudio Rossetti A.O. Ospedale Niguarda Ca' Granda (ended 31Dec2015)
Oncologia Medica Falck Dip. Oncologico Piazza Ospedale Maggiore, 3
20162 Milano Italy
185 Dr.Roberto Sabbatini A.O.U. di Modena - Policlinico Oncologia - Padiglione Beccaria Direttore: Prof. Stefano Cascinu (since 1Nov2015) Dip. Oncologia ed Ematologia (DAI 4) Via del Pozzo, 71 - Ingresso 33
41124 Modena Italy
186 Dr.Giovanni Rosti AULSS 09 Treviso Oncologia Medica Ospedale Regionale Cà Foncello Piazza Ospedale, 1
31100 Treviso Italy
187 Dr.Sergio Bracarda AUSL 8 Arezzo Centro Oncologico Direttore: Dr. Sergio Bracarda Ospedale San Donato Via P. Nenni, 20
52100 Arezzo Italy
188 Prof.Giacomo Cartenì A.O.R.N. Antonio Cardarelli Oncologia Medica Direttore: Dr. Giacomo Cartenì Dip. Oncoematologico
80131 Napoli Italy
Appendix to Clinical Study Synopsis
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Via Cardarelli, 9
189 Dr.Secondo Lastoria Istituto Nazionale Studio-Cura Tumori Fondazione G. Pascale
Medicina Nucleare e Terapia Metabolica Dip. Diagnostica per Immagini, Terapia Radiante e Metabolica Via M. Semmola, 1
80131 Napoli Italy
190 Dr.Orazio Caffo APSS Trento Oncologia Medica Direttore: Dr. Enzo Galligioni Ospedale Santa Chiara Largo Medaglie d'Oro, 9
38122 Trento Italy
191 Prof.Gianmario Sambuceti
IRCCS A.O.U. San Martino IST Ist. Nazionale Ricerca Cancro
Medicina Nucleare Dip. Tecnologie Radiologiche - Ospedale San Martino Largo R. Benzi, 10
16132 Genova Italy
192 Prof.Saverio Cinieri AUSL Brindisi Oncologia Presidio Ospedaliero Di Summa-Perrino Strada Statale 7 per Mesagne
72100 Brindisi Italy
193 Prof.Carlo Ludovico Maini
IRCCS Istituti Fisioterapici Ospitalieri
Medicina Nucleare IRE Istituto Nazionale Tumori Regina Elena Via E. Chianesi, 53
00144 Roma Italy
194 Prof.Francesco Montorsi
IRCCS Fondazione San Raffaele
Urologia Istituto Scientifico Universitario San Raffaele Via Olgettina, 60
20132 Milano Italy
195 Dr.Vittorina Zagonel IRCCS Istituto Oncologico Veneto (IOV)
Oncologia Medica 1 Direttore: Dr. Vittorina Zagonel Area di Oncologia Clinica e Sperimentale Via Gattamelata, 64
35128 Padova Italy
196 Dr.Antonio Piga ASL Cagliari Oncologia Medica Direttore f.f. Dr. Efisio Defraia Ospedale Oncologico Businco Via Jenner, 1
09125 Cagliari Italy
197 Prof.Paolo Marchetti A.O. Sant'Andrea Oncologia Medica Direttore: Prof. Paolo Marchetti Dip. Scienze Oncologiche Via di Grottarossa, 1035-1039
00189 Roma Italy
198 Dr.Lucio Mango A.O. San Camillo-Forlanini Medicina Nucleare Direttore: Dr. Lucio Mango Via Portuense, 332
00149 Roma Italy
199 Prof.Evaristo Maiello IRCCS Casa Sollievo della Sofferenza
Oncologia Medica Direttore: Dr. Evaristo Maiello Dip. Onco-Ematologia Viale Cappuccini, 1 - San Giovanni Rotondo
71013 Foggia Italy
200 Prof.Carlo Antonio Mario Barone
Università Cattolica del Sacro Cuore
Oncologia Medica Direttore: Prof. Carlo Antonio Mario Barone Policlinico A. Gemelli Largo A. Gemelli, 8
00168 Roma Italy
201 Prof.Alberto Pupi A.O.U. Careggi Medicina Nucleare Biomolecolare Direttore: Prof. Alberto Pupi
50134 Firenze Italy
Appendix to Clinical Study Synopsis
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Dip. Servizi - Area Diagnostica per Immagini Largo Brambilla, 3
202 Dr.Marco Ferdeghini A.O.U. Integrata Verona Medicina Nucleare Ospedale Civile Maggiore (Borgo Trento) Piazzale A.Stefani, 1
37126 Verona Italy
203 Mr. Dr.Miguel Jiménez Ríos
Instituto Nacional de Cancerología
Av. San Fernando N° 22 Col. Sección XVI Delegación Tlalpan
14080 México Mexico
204 Mrs. Dr.Raquel Gerson Cwilich
Centro de Cancer ABC Sur 128 No. 143 Col. Las Américas
01120 Mexico, D.F. Mexico
205 Dr.A.J.M. van den Eertwegh
Academisch Ziekenhuis Vrije Universiteit
Afd. Int./Oncologie, De Boelelaan 1117
1081 HV AMSTERDAM Netherlands
206 Dhr.Dr.T.A. Roeleveld
Noord West Ziekenhuisgroep-Medisch Centrum Alkmaar
Wilhelminalaan 12 Afd. Urologie
1815 JD ALKMAAR Netherlands
207 Dr.J.L.L.M. Coenen Isala Afdeling Interne Geneeskunde, Dr. van Heesweg 2
8025 AB ZWOLLE Netherlands
208 Dhr. Prof. Dr.W.J.G. Oyen
Universitair Medisch Centrum St. Radboud
Afd. Medische Oncologie Huispost 550 Geert Grooteplein 8,
6525 GA NIJMEGEN Netherlands
209 Mrs. Dr.S. Osanto Leids Universitair Medisch Centrum
Albinusdreef 2 2333 ZA LEIDEN Netherlands
210 MDDaniel Heinrich Akershus Universitetssykehus HF
Akershus Universitetssykehus Oncology dept. Sykehusveien 25
1478 Lørenskog Norway
211 Dr.Carsten Nieder Nordlandssykehuset HF Nordlandssykehuset HF, Bodø Medisinsk avdeling Postboks 1480 Besøksadresse: Prinsens gate 164
8092 Bodø Norway
212 Dr.Svein Helle Helse Bergen HF Haukeland universitetssjukehus
Oncology dept. Jonas Liesvej 65 Postbox 1
5021 Bergen Norway
213 MD, PhDSophie Fossaa
Oslo universitetssykehus HF Radiumhospitalet
Oslo universitetssykehus HF, Radiumhospitalet Postbox 4953 Nydalen Besøksadr.: Ullernchausseen 70, Montebello 0379, Oslo
0424 Oslo Norway
214 MDSigurd Oerstavik Oslo Universitetssykehus HF, Ullevål
Oslo Universitetshospital HF Kreftsenteret Kirkeveien 166
Oslo Norway
215 MDBjoerg Aksnessaether
Helse Møre og Romsdal HF Helse Møre og Romsdal HF Kreftavdelinga Åsehaugen 5
6026 Ålesund Norway
216 Prof.Tomasz Demkow
Centrum Onkologii - Instytut im. M.Sklodowskiej-Curie
ul. W.K. Roentgena 5 ul. Wawelska 15B, 02-034 Warszawa Office address
02-781 Warszawa Poland
217 DrAnna Sowa-Staszczak
Szpital Uniwersytecki w Krakowie
ul. Kopernika 36 31-501 Krakow Poland
218 DrPiotr Jarzemski Szpital Uniwersytecki Nr 2 im. J. Bizela
Oddzial Urologii i Urologii Onkologicznej z Poddodzialem Chem. ul. Ujejskiego 75
85-165 Bydgoszcz Poland
219 Prof.Barbara Jarzab Centrum Onkologii - Instytut ul. Wybrzeze Armii Krajowej 15
44-100 Gliwice Poland
220 DrDorota Filarska Szpitale Wojewódzkie Sp. zo.o. dawny Szpital Morski im. PCK
ul. Powstania Styczniowego 1
81-519 Gdynia Poland
Appendix to Clinical Study Synopsis
Page 12 of 12
221 DrTomasz Filipowski Bialostockie Centrum Onkologii im. M. Sklodowskiej-Curie
ul. Ogrodowa 12 15-027 Bialystok Poland
222 DrElzbieta Nowakowska
NZOZ Centrum Medyczne HCP Sp. zo.o.
ul. 28 czerwca 1956r. 194 61-485 Poznan Poland
223 DrElżbieta Senkus-Konefka
Uniwersyteckie Centrum Kliniczne
ul. Debinki 7 80-952 Gdansk Poland
224 Prof.Janusz Skowronek
Wielkopolskie Centrum Onkologii
ul. Garbary 15 61-866 Poznan Poland
225 DrLech Stachurski Poland
226 DrS A Ivanov Research Centre of X-ray and Radiology
Ministry of Health of the RF Urology Department ul Profsouznaya 86
117837 Moscow Russian Federation
227 Mr. Prof.Oleg Karyakin
National Medical Research Radiology Center
Department of radio surgical treatment by sheltered radionuclides 4, Koroleva st.
249036 Obninsk Russian Federation
228 Prof.Vsevolod Matveev
Russian Research Oncology Centre n.a. N.N Blokhin of RAMS
24, Kashirskoe shosse 115478 Moscow Russian Federation
229 n/a National Medical Research Radiology Center
Department of radio surgical treatment by sheltered radionuclides 4, Koroleva st.
249036 Obninsk Russian Federation
230 n/a National Medical Research Radiology Center
Local ethical committee for clinical trials Medical Radiological Research Centre of RAMS 4, Koroleva st.
249036 Obninsk Russian Federation
231 ProfSten Nilsson Karolinska Universitetssjukhuset i Solna
Radiumhemmet Kliniken för onkologi
171 76 Stockholm Sweden
232 MD, PhDJan Tennvall Skånes Universitetssjukhus Getingevägen 4 221 85 Lund Sweden
233 DrAnna Laurell Akademiska Sjukhuset Onkologmottagningen 751 85 Uppsala Sweden
234 DocMaria Albertsson Universitetssjukhuset i Linköping
Onkologiska kliniken Garnisonsvägen 10
581 85 Linköping Sweden
235 Dr.Camilla Thellenberg Karlsson
Norrlands Universitetssjukhus, Umeå
Cancercentrum, NUS 901 85 Umeå Sweden
236 DrMats Andén Länssjukhuset i Kalmar Onkologienheten / Kirurgiska kliniken
391 85 Kalmar Sweden
237 DrLars Beckman Länssjukhuset Sundsvall-Härnösand
Onkologkliniken 851 86 Sundsvall Sweden
238 DrJana Orlovskaja Mälarsjukhuset Onkologkliniken Sörmland Klostergatan 28
633 52 Eskilstuna Sweden
239 DrClaes Ginman Centralsjukhuset i Karlstad Onkologkliniken 651 85 Karlstad Sweden
240 MDBo Lennernäs Sahlgrenska Universitetssjukhuset
Jubileumskliniken Allmän onkologi
413 45 Göteborg Sweden
241 DrBengt Johansson Örebro Universitetssjukhus Onkologiska kliniken 715 92 Örebro Sweden
Appendix to Clinical Study Synopsis
Product Identification Information
Product Type
Drug
US Brand/Trade Name(s)
Xofigo
Brand/Trade Name(s) ex-US
Xofigo
Generic Name
radium Ra 223 dichloride
Main Product Company Code
BAY88-8223
Other Company Code(s)
Alpharadin
Chemical Description
Radium-223 dichloride
Other Product Aliases
Radium-223 chloride
Date of last Update/Change: 09 Jul 2015