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.
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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
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 2 of 10
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.
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 3 of 10
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.
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 4 of 10
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
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 5 of 10
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
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 6 of 10
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%).
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 7 of 10
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%),
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 8 of 10
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:
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 9 of 10
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:
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).
Clinical Trial Results Synopsis 02-Feb-2017 Study no. 16216 Page: 10 of 10
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.
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
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
Page 8 of 12
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
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
Oncologia Medica ed Ematologia Direttore: Dr. Armando
20089 Milano Italy
Appendix to Clinical Study Synopsis
Page 9 of 12
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)
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