A Phase III Study of Radium-223 Dichloride in Patients With Symptomatic Hormone Refractory Prostate Cancer With Skeletal Metastases (ALSYMPCA)

A Double-blind, Randomised, Multiple Dose, Phase III, Multicentre Study of Alpharadin in the Treatment of Patients With Symptomatic Hormone Refractory Prostate Cancer With Skeletal Metastases

ALSYMPCA (ALpharadin in SYMPtomatic Prostate CAncer) is an international Phase III clinical study to evaluate the efficacy and safety of Radium-223 dichloride in patients with hormone refractory prostate cancer and skeletal metastases.

Study Overview

• Status: Completed
• Conditions: Bone Metastases; Hormone Refractory Prostate Cancer
• Intervention / Treatment: Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: Best standard of care (BSoC); Drug: Placebo

Detailed Description

The aim of the study was to compare, in patients with symptomatic hormone refractory prostate cancer (HRPC) and skeletal metastases, the efficacy of best standard of care plus Radium-223 dichloride versus best standard of care plus placebo, with the primary efficacy endpoint being overall survival (OS).

Patients were randomised in a 2:1 allocation ratio (Radium-223 dichloride:Placebo). The study treatment consisted of 6 intravenous administrations of Radium-223 dichloride or placebo (saline) each separated by an interval of 4 weeks. The patient were followed until 3 years after first study drug administration.

Within the U.S., the trial was conducted under an IND sponsored by Bayer HealthCare Pharmaceuticals.

All patients received BSoC (Best Standard of Care).

This study has the original PCD as 14 October 2010, when a total of 316 deaths had been observed; this resulted in the Independent Data Monitoring Committee's (IDMC's) recommendation to stop the study as the primary efficacy analysis of overall survival had crossed the pre-specified boundary for efficacy. Later an updated analysis of primary endpoint in the first addendum was done with cut-off of 15 July 2011.

• Study Type: Interventional
• Enrollment (Actual): 921
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
    • Randwick, New South Wales, Australia, 2031
    • St Leonards, New South Wales, Australia, 2065
    • Sydney, New South Wales, Australia, 2010
    • Wahroonga, New South Wales, Australia, 2076
    • Wollongong, New South Wales, Australia, 2521
  • Queensland
    • Brisbane, Queensland, Australia, 4029
    • Toowoomba, Queensland, Australia, 4350
  • South Australia
    • Adelaide, South Australia, Australia, 5000
    • Adelaide, South Australia, Australia, 5011
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
• Belgium
  • Kortrijk, Belgium, 8500
  • Ottignies, Belgium, 1340
• Brazil
  • Belo Horizonte, Brazil, 30380490
  • Rio de Janeiro, Brazil, 20551 030
  • Sao Paulo, Brazil, 05403-900
  • Bahia
    • Salvador, Bahia, Brazil, 41830-492
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30110-090
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784400
    • Piracicaba, Sao Paulo, Brazil
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
  • Ontario
    • London, Ontario, Canada, N6A 4G5
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M4N 3M5
• Czech Republic
  • Brno, Czech Republic, 65653
  • Chomutov, Czech Republic, 430 12
  • Olomouc, Czech Republic, 775 20
  • Ostrava, Czech Republic, 708 52
  • Plzen - Bory, Czech Republic, 305 99
  • Praha 4, Czech Republic, 140 59
  • Usti nad Labem, Czech Republic, 401 13
• France
  • La Roche Sur Yon, France, 85925
  • Montbeliard, France, 25209
  • Saint Cloud, France, 92210
• Germany
  • Berlin, Germany, 10967
  • Berlin, Germany, 14197
  • Hamburg, Germany, 20246
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany, 89075
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
    • Marburg, Hessen, Germany, 35043
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37099
    • Hannover, Niedersachsen, Germany, 30625
  • Nordrhein-Westfalen
    • Dortmund, Nordrhein-Westfalen, Germany, 44137
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
• Hong Kong
  • Chai Wan, Hong Kong
  • Hong Kong, Hong Kong
  • Hongkong, Hong Kong
  • Kowloon, Hong Kong
• Israel
  • Beer Sheva, Israel, 8410101
  • Kfar Saba, Israel, 4428164
  • Tel Aviv, Israel, 6423906
  • Zrifin, Israel, 6093000
• Italy
  • Bergamo, Italy, 24128
  • Milano, Italy, 20162
  • Reggio Emilia, Italy, 42123
  • Forlì
    • Meldola, Forlì, Italy, 47014
  • Torino
    • Candiolo, Torino, Italy, 10060
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
  • Nijmegen, Netherlands, 6532 SZ
  • Rotterdam, Netherlands, 3015 CE
• Norway
  • Bergen, Norway, 5021
  • Bodø, Norway, 8092
  • Kristiansand, Norway, N-4604
  • Oslo, Norway, 0450
  • Oslo, Norway, N-0310
  • Tromsø, Norway, 9038
  • Trondheim, Norway, 7006
  • Ålesund, Norway, 6026
• Poland
  • Bydgoszcz, Poland, 85-165
  • Gliwice, Poland, 44-101
  • Kielce, Poland, 25-734
  • Krakow, Poland, 31-051
  • Luiblin, Poland, 20-954
  • Warszawa, Poland, 02-781
  • Wroclaw, Poland, 50 - 556
  • Wroclaw, Poland, 50-981
• Singapore
  • Singapore, Singapore, 308433
  • Singapore, Singapore, 258499
• Slovakia
  • Banska Bystrica, Slovakia, 97517
  • Bratislava, Slovakia, 82606
  • Bratislava, Slovakia, 83305
  • Martin, Slovakia, 03659
  • Presov, Slovakia, 08181
  • Trnava, Slovakia, 917 01
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08025
  • Córdoba, Spain, 14004
  • Pamplona, Spain, 31008
  • Valencia, Spain, 46026
  • Zaragoza, Spain, 50009
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
• Sweden
  • Göteborg, Sweden, 413 45
  • Jönköping, Sweden, 551 85
  • Kalmar, Sweden, 391 85
  • Malmö, Sweden, 205 02
  • Sandviken, Sweden, 80187
  • Stockholm, Sweden, 171 76
  • Sundsvall, Sweden, 851 86
  • Umeå, Sweden, 901 85
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
  • Brighton, United Kingdom, BN2 5BD
  • Bristol, United Kingdom, BS2 8ED
  • Cardiff, United Kingdom
  • Derby, United Kingdom, DE22 3NE
  • Hull, United Kingdom, HU16 5JQ
  • Leeds, United Kingdom, LS9 7TF
  • Manchester, United Kingdom, M20 4BX
  • Northwood, United Kingdom, HA6 2RN
  • Plymouth, United Kingdom, PL6 8DH
  • Sheffield, United Kingdom, S10 2SJ
  • Southampton, United Kingdom, SO16 6YD
  • Wolverhampton, United Kingdom, WV10 0QP
  • Essex
    • Romford, Essex, United Kingdom, RM7 0AG
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
  • Merseyside
    • Bebington, Merseyside, United Kingdom, CH63 4JY
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
  • Somerset
    • Taunton, Somerset, United Kingdom, TA1 5DA
  • Suffolk
    • Ipswich, Suffolk, United Kingdom, IP4 5PD
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
    • Sutton, Surrey, United Kingdom, SM2 5PT
  • Warwickshire
    • Coventry, Warwickshire, United Kingdom, CV2 2DX
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
• United States
  • California
    • Los Angeles, California, United States, 90048-0750
    • Roseville, California, United States, 95661
  • Florida
    • Tampa, Florida, United States, 33612
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Missouri
    • St. Louis, Missouri, United States, 63110
  • Nevada
    • Las Vegas, Nevada, United States, 89169
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Known hormone refractory disease
• Multiple skeletal metastases (≥ 2 hot spots) on bone scintigraphy
• No intention to use cytotoxic chemotherapy within the next 6 months
• Either regular (not occasional) analgesic medication use for cancer related bone pain or treatment with EBRT (External Beam Radiation Therapy) for bone pain

Exclusion Criteria:

• Treatment with an investigational drug within previous 4 weeks, or planned during the treatment period
• Eligible for first course of docetaxel, i.e. patients who are fit enough, willing and where docetaxel is available
• Treatment with cytotoxic chemotherapy within previous 4 weeks, or planned during the treatment period, or failure to recover from adverse events due to cytotoxic chemotherapy administered more than 4 weeks ago
• Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks
• Other malignancy treated within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer)
• History of visceral metastasis, or visceral metastases as assessed by abdominal/pelvic CT or chest x-ray within previous 8 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radium-223 dichloride (Xofigo, BAY88-8223); Participants received radium-223 50 kilo Becquerel (kBq)/kg body weight (b.w.) for 6 intravenous (IV) administrations separated by 4 weeks intervals plus Best Standard of Care (BSoC).	Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Radium-223 dichloride 50 kBq/kg b.w., 6 IV administrations separated by 4 weeks intervals.; Other Names: Alpharadin; Drug: Best standard of care (BSoC); Best standard of care is regarded as the routine standard of care at each center, for example local EBRT (External Beam Radiation Therapy), corticosteroids, antiandrogens, estrogens (e.g., stilboestrol), estramustine or ketoconazole.
Placebo Comparator: Placebo; Participants received isotonic saline for 6 IV administrations separated by 4 weeks intervals plus Best Standard of Care (BSoC).	Drug: Best standard of care (BSoC); Best standard of care is regarded as the routine standard of care at each center, for example local EBRT (External Beam Radiation Therapy), corticosteroids, antiandrogens, estrogens (e.g., stilboestrol), estramustine or ketoconazole.; Drug: Placebo; Isotonic saline 6 IV administrations separated by 4 weeks intervals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival was defined as the time from date of randomization to the date of death.	From randomization to death due to any cause until approximately 3 years after start of enrollment, the data was collected up to the second data analysis date (15 JUL 2011)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Total Alkaline Phosphatase (ALP) Progression	The time from the first study drug administration to when ALP progression was observed, defined as: 1) In subjects with no ALP decline from baseline; a greater than or equal to 25% increase from baseline value and an increase in absolute value of greater than or equal to 2 ng/mL, at least 12 weeks from baseline; 2) In subjects with initial ALP decline from baseline; the time from start of treatment to first ALP increase that is greater than or equal to 25% increase and at least 2 ng/mL above the nadir value, which was confirmed by a second value obtained 3 or more weeks later	From randomization to first ALP progression until approximately 3 years after start of enrollment
Percentage of Participants With Total ALP Response at Week 12	ALP levels were measured in participants' blood at Week 12 and compared to baseline values. A confirmed total ALP response (either >/= 30% or 50% reduction from baseline) was confirmed by a second total ALP value approximately 4 weeks later.	At Baseline and Week 12
Percentage of Participants With Total ALP Response at End of Treatment (EOT; Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)	ALP levels were measured in participants' blood at EOT (Week 24) and compared to baseline values. A confirmed total ALP response (>/=50% reduction from baseline) was confirmed by a second total ALP value approximately 4 weeks later.	At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase)
Percentage of Participants With Total ALP Normalization at Week 12	The return of total ALP value to within normal range at 12 weeks in 2 consecutive measurements (at least 2 weeks apart) after start of treatment in subjects who had ALP above the upper limit of normal (ULN) at baseline.	At Baseline and Week 12
Percentage Change From Baseline in Total ALP at Week 12	ALP level was measured in subject's blood at Week 12 and the percent change from the baseline value was calculated (ALP level at week 12 minus ALP level at baseline)/(ALP level at baseline)*100	At Baseline and Week 12
Maximum Percentage Decrease From Baseline in Total ALP up to Week 12	ALP level was measured in participant's blood up to week 12 and the maximum percent decrease from the baseline up to Week 12 value was calculated as the minimum value of [(ALP level up to week 12 minus ALP level at baseline)/(ALP level at baseline)*100] by participant, and set to zero if no decrease from baseline.	From baseline to Week 12
Percentage Change From Baseline in Total ALP at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)	ALP level was measured in subject's blood at EOT (Week 24) and the percent change from the baseline value was calculated (ALP level at EOT minus ALP level at baseline)/(ALP level at baseline)*100	At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase)
Maximum Percentage Decrease From Baseline in Total ALP During the 24 Week Treatment	ALP level was measured in participant's blood during the 24 week treatment (up to EOT) and the maximum percent decrease from baseline during the 24 week treatment value was calculated as the minimum value of [(ALP level up to week 24 minus ALP level at baseline)/(ALP level at baseline)*100] by participant, and set to zero if no decrease from baseline.	From baseline During the 24 Week Treatment
Time to Prostate Specific Antigen (PSA) Progression	The time from the first study drug administration to when PSA progression was observed, defined as: 1) In subjects with no PSA decline from baseline; a greater than or equal to 25% increase from baseline value and an increase in absolute value of greater than or equal to 2 ng/mL, at least 12 weeks from baseline; 2) In subjects with initial PSA decline from baseline; the time from start of treatment to first PSA increase that is greater than or equal to 25% increase and at least 2 ng/mL above the nadir value, which was confirmed by a second value obtained 3 or more weeks later	From randomization to first PSA progression until approximately 3 years after start of enrollment
Percentage of Participants With PSA Response at Week 12	PSA levels were measured in participants' blood at Week 12 and compared to baseline values. A confirmed PSA response (>/=50% reduction from baseline) was confirmed by a second PSA value approximately 4 weeks later.	At Baseline and Week 12
Percentage of Participants With PSA Response at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)	PSA levels were measured in participants' blood at EOT (Week 24) and compared to baseline values. A confirmed PSA response (>/=50% reduction from baseline) was confirmed by a second PSA value approximately 4 weeks later.	At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase)
Percentage Change From Baseline in PSA at Week 12	PSA level was measured in subject's blood at Week 12 and the percent change from the baseline value was calculated (PSA level at week 12 minus PSA level at baseline)/(PSA level at baseline)*100	At Baseline and Week 12
Maximum Percentage Decrease From Baseline in PSA up to Week 12	PSA level was measured in participant's blood up to Week 12 and the maximum percent decrease from the baseline up to week 12 value was calculated as the minimum value of [(PSA level up to week 12 minus PSA level at baseline)/(PSA level at baseline)*100] by participant, and set to zero if no decrease from baseline.	From baseline up to Week 12
Percentage Change From Baseline in PSA at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)	PSA level was measured in subject's blood at EOT (Week 24) and the percent change from the baseline value was calculated (PSA level at EOT minus PSA level at baseline)/(PSA level at baseline)*100	At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase)
Maximum Percentage Decrease From Baseline in PSA Response During the 24 Week Treatment Period	PSA level was measured in participant's blood during the 24 week treatment (up to EOT) and the maximum percent decrease from baseline during the 24 Week treatment value was calculated as the minimum value of [(PSA level up to week 24 minus PSA level at baseline)/(PSA level at baseline)*100] by participant, and set to zero if no decrease from baseline.	From baseline to End of Treatment (Week 24; 4 weeks post last injection)
Time to First Skeletal Related Event (SRE)	A skeletal related event is the use of external beam radiotherapy to relieve skeletal symptoms or the occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral) or the occurrence of spinal cord compression or a tumour related orthopaedic surgical intervention. For all other events, the start date of the event/medication/therapy was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.	From randomization to first first SRE until approximately 3 years after start of enrollment
Time to Occurrence of First Use of External Beam Radiation Therapy (EBRT) to Relieve Skeletal Symptoms	The start date of therapy was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.	From randomization to first EBRT until approximately 3 years after start of enrollment
Time to Occurrence of First Use of Radioisotopes to Relieve Skeletal Symptoms	The start date of the radioisotopes was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.	From randomization to first use of radioisotopes until approximately 3 years after start of enrollment
Time to Occurrence of First New Symptomatic Pathological Bone Fractures, Vertebral and Non-vertebral	The start date of the event was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.	From randomization to occurrence of first new symptomatic pathological bone fractures until approximately 3 years after start of enrollment
Time to Occurrence of First Tumor Related Orthopedic Surgical Intervention	The start date of the intervention was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.	From randomization to occurrence of first tumor related orthopedic surgical intervention until approximately 3 years after start of enrollment
Time to Occurrence of First Spinal Cord Compression	The start date of the compression was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.	From randomization to first spinal cord compression until approximately 3 years after start of enrollment
Time to Occurrence of First Start of Any Other Anti-cancer Treatment	The start date of the treatment was used as the time of the event. If an event has not occurred at the time of the analysis or the patient has been lost to follow-up, the time-to-event variables will be censored at the last disease assessment date.	From randomization to first start of any other anti-cancer treatment until approximately 3 years after start of enrollment
Time to Occurrence of First Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least 2 Points From Baseline	ECOG scores were: 0 = fully active; 1 = restricted in physically strenuous activity; 2 = ambulatory and capable of all self-care but unable to work; 3 = capable of only limited self-care; 4 = completely disabled; 5 = death. The visit at which a 2-point or more deterioration in PS was observed was the time of the event. ECOG was assessed at every visit. If a marked deterioration in PS has not occurred at the time of the analysis or the participant was lost to follow-up, the time-to-event variables were censored at the last assessment date.	From randomization to first deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) until approximately 3 years after start of enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 0.	ECOG PS was defined as: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work, office work); 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; or 5 = Dead.	Week 0
Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 8.	ECOG PS was defined as: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work, office work); 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; or 5 = Dead.	Week 8
Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 16.	ECOG PS was defined as: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work, office work); 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; or 5 = Dead.	Week 16
Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 24.	ECOG PS was defined as: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work, office work); 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; or 5 = Dead.	Week 24
Absolute Scores for Functional Assessment of Cancer Therapy - Prostate (FACT-P) Trial Outcome Index (TOI)	The FACT-P was 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being. It was supplemented by 12 questions relating to prostate cancer. The absolute score for the FACT-P TOI domain (physical and social well-being and prostate specific score) was calculated for each visit. Prostate Cancer Trial Outcome Index (TOI): Physical Well-being (PWB) + Functional Well-being (FWB) + Prostate Cancer (PCS). Score ranges from 0 (worst) to 104 (best).	Baseline, Week 16, Week 24, and Follow-up Visit 2 (Week 42)
Changes From Baseline for FACT-P Trial Outcome Index (TOI) at Week 16, Week 24, and Follow-up Visit 2 (Week 42)	The FACT-P was 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being. It was supplemented by 12 questions relating to prostate cancer. The absolute score for the FACT-P TOI domain (physical and social well-being and prostate specific score) was calculated for each visit. Possible scores were 0 to 104; the higher the score, the better the quality of life. The changes from baseline (range -104 to 104) in the domain FACT-P TOI were summarized using descriptive statistics at Week 16, Week 24, and Follow-up Visit 2.	Baseline, Week 16, Week 24, and Follow-up Visit 2 (Week 42)
Absolute Scores for Physical Well Being, Social/Family Well Being, Emotional Well Being, Functional Well Being, and the Prostate Cancer Subscale at Week 16	The FACT-P was 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being and was supplemented by 12 questions relating to prostate cancer. Possible scores for each subscale were 0 to 28; 0 to 28; 0 to 24; 0 to 28; and 0 to 48, respectively. All FACT-P items are scored on a scale of 0-4 representing the extent to which the item reflects the experience of the individual completing the instrument (0 - Not at all; 4 - Very much). Higher scores indicate better quality of life. The absolute score of the FACT-P total score was calculated at Week 16.	At Week 16
Absolute Scores for Physical Well Being, Social/Family Well Being, Emotional Well Being, Functional Well Being, and the Prostate Cancer Subscale at Week 24	The FACT-P was 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being and was supplemented by 12 questions relating to prostate cancer. Possible scores for each subscale were 0 to 28; 0 to 28; 0 to 24; 0 to 28; and 0 to 48, respectively. All FACT-P items are scored on a scale of 0-4 representing the extent to which the item reflects the experience of the individual completing the instrument (0 - Not at all; 4 - Very much). Higher scores indicate better quality of life. The absolute score of the FACT-P total score was calculated at Week 24.	At Week 24
Absolute Scores for Physical Well Being, Social/Family Well Being, Emotional Well Being, Functional Well Being, and the Prostate Cancer Subscale at Follow-up Visit 2 (Week 42)	The FACT-P was 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being and was supplemented by 12 questions relating to prostate cancer. Possible scores for each subscale were 0 to 28; 0 to 28; 0 to 24; 0 to 28; and 0 to 48, respectively. All FACT-P items are scored on a scale of 0-4 representing the extent to which the item reflects the experience of the individual completing the instrument (0 - Not at all; 4 - Very much). Higher scores indicate better quality of life. The absolute score of the FACT-P total score was calculated at Follow-up Visit 2.	At Follow-up Visit 2 (Week 42)
Absolute Scores for FACT-P Total Score at Week 16, Week 24, and Follow-up Visit 2 (Week 42)	The FACT-P was 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being. It was supplemented by 12 questions relating to prostate cancer. The absolute score of the FACT-P total score (physical, social/family, emotional, and functional well-being and prostate specific score) was calculated at Week 16, Week 24, and Follow-up Visit 2.FACT-P Total Score: Physical Well-being (PWB) + Social/Family Well-being (SWB) + Emotional Well-being (EWB) + Functional Well-being (FWB) + Prostate Cancer (PCS). Score ranges from 0 (worst) to 156 (best).	At Week 16, Week 24, and Follow-up Visit 2 (Week 42)
Change From Baseline for FACT-P Total Score at Week 16, Week 24, and Follow-up Visit 2 (Week 42)	The FACT-P was 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being. It was supplemented by 12 questions relating to prostate cancer. Total possible score was 156; a higher score indicates a better quality of life. The changes from baseline in the FACT-P total score (physical, social/family, emotional, and functional well-being and prostate specific score) were calculated at Week 16, Week 24, and Follow-up Visit 2. Possible range was -156 to 156.	Baseline, Week 16, Week 24, and Follow-up Visit 2 (week 42)
Absolute Scores for Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Week 16, Week 24, and Follow-up Visit 2 (Week 42)	The FACT-G instrument consisted of 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being. The FACT-G absolute total score (physical, social/family, emotional, and functional well-being) was calculated at Week 16, Week 24, and Follow-up Visit 2. FACT-G Total Score: Physical Well-being (PWB) + Social/Family Well-being (SWB) + Emotional Well-being (EWB) + Functional Well-being (FWB). Score ranges from 0 (worst) to 108 (best).	At Week 16, Week 24, and Follow-up Visit 2 (Week 42)
Change From Baseline for FACT-G Total Score at Week 16, Week 24, and Follow-up Visit 2 (Week 42)	The FACT-G instrument consisted of 27 questions relating to 4 domains: physical, social/family, emotional, and functional well-being. Total possible score was 108; a higher score indicates a better quality of life. The changes from baseline in the FACT-G total score (physical, social/family, emotional, and functional well-being) were calculated at Week 16, Week 24, and Follow-up Visit 2. Possible range was -108 to 108.	Baseline, Week 16, Week 24, and Follow-up Visit 2 (Week 42)
Number of Participants in the Euro Quality of Life (EQ-5D) Components for Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression at Week 16	The EQ-5D questionnaire was given to the subject at each visit. The EQ-5D questionnaire consisted of 5 ordinal categorical responses (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Number of participants with EQ-5D at Week 16, as measured by this questionnaire, was counted. The scores for the EQ-5D dimensions are assigned according to the level of problems reported (1 'no problems'; 2 'some problems'; 3 'extreme problems').	Week 16
Number of Participants in the Euro Quality of Life (EQ-5D) Components for Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression at Week 24	The EQ-5D questionnaire was given to the subject at each visit. The EQ-5D questionnaire consisted of 5 ordinal categorical responses (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Number of participants with EQ-5D at Week 24, as measured by this questionnaire, was counted. The scores for the EQ-5D dimensions are assigned according to the level of problems reported (1 'no problems'; 2 'some problems'; 3 'extreme problems').	Week 24
Number of Participants in the Euro Quality of Life (EQ-5D) Components for Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression at Follow-up Visit 8 (Week 139)	The EQ-5D questionnaire was given to the subject at each visit. The EQ-5D questionnaire consisted of 5 ordinal categorical responses (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Number of participants with EQ-5D at follow-up visit 8, as measured by this questionnaire, was counted. The scores for the EQ-5D dimensions are assigned according to the level of problems reported (1 'no problems'; 2 'some problems'; 3 'extreme problems').	Follow-up Visit 8 (Week 139)

Collaborators and Investigators

• Sponsor: Bayer
• Investigators: Study Chair: Christopher Parker, MD, The Royal Marsden Hospital, UK

Publications and helpful links

General Publications

• Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall'Oglio M, Franzen L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland OS, Sartor O; ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213-23. doi: 10.1056/NEJMoa1213755.
• Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J, Bottomley D, Nilsson S, Vogelzang NJ, Fang F, Wahba M, Aksnes AK, Parker C. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014 Nov;15(12):1397-406. doi: 10.1016/S1470-2045(14)70474-7. Epub 2014 Oct 17.
• Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD, Chodacki A, Wiechno P, Logue J, Widmark A, Johannessen DC, Hoskin P, James ND, Solberg A, Syndikus I, Vogelzang NJ, O'Bryan-Tear CG, Shan M, Bruland OS, Parker C. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014 Jun;15(7):738-46. doi: 10.1016/S1470-2045(14)70183-4. Epub 2014 May 13.
• Delacruz A, Arauz G, Curley T, Lindo A, Jensen T. Nursing management of patients with castration-resistant prostate cancer undergoing radium-223 dichloride treatment. Clin J Oncol Nurs. 2015 Apr;19(2):E31-5. doi: 10.1188/15.CJON.E31-E35.
• Humm JL, Sartor O, Parker C, Bruland OS, Macklis R. Radium-223 in the treatment of osteoblastic metastases: a critical clinical review. Int J Radiat Oncol Biol Phys. 2015 Apr 1;91(5):898-906. doi: 10.1016/j.ijrobp.2014.12.061.
• Nilsson S. Alpha-emitter radium-223 in the management of solid tumors: current status and future directions. Am Soc Clin Oncol Educ Book. 2014:e132-9. doi: 10.14694/EdBook_AM.2014.34.e132.
• Den RB, Doyle LA, Knudsen KE. Practical guide to the use of radium 223 dichloride. Can J Urol. 2014 Apr;21(2 Supp 1):70-6.
• Shirley M, McCormack PL. Radium-223 dichloride: a review of its use in patients with castration-resistant prostate cancer with symptomatic bone metastases. Drugs. 2014 Apr;74(5):579-86. doi: 10.1007/s40265-014-0198-4.
• Wissing MD, van Leeuwen FW, van der Pluijm G, Gelderblom H. Radium-223 chloride: Extending life in prostate cancer patients by treating bone metastases. Clin Cancer Res. 2013 Nov 1;19(21):5822-7. doi: 10.1158/1078-0432.CCR-13-1896. Epub 2013 Sep 19.
• Joung JY, Ha YS, Kim IY. Radium Ra 223 dichloride in castration-resistant prostate cancer. Drugs Today (Barc). 2013 Aug;49(8):483-90. doi: 10.1358/dot.2013.49.8.1968670.
• Parker C, Zhan L, Cislo P, Reuning-Scherer J, Vogelzang NJ, Nilsson S, Sartor O, O'Sullivan JM, Coleman RE. Effect of radium-223 dichloride (Ra-223) on hospitalisation: An analysis from the phase 3 randomised Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. Eur J Cancer. 2017 Jan;71:1-6. doi: 10.1016/j.ejca.2016.10.020. Epub 2016 Dec 6.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: June 17, 2008
• First Submitted That Met QC Criteria: June 17, 2008
• First Posted (Estimate): June 18, 2008

Study Record Updates

• Last Update Posted (Estimate): May 27, 2016
• Last Update Submitted That Met QC Criteria: April 27, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Radium-223; Hormone Refractory Prostate Cancer; Bone Metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Prostatic Neoplasms; Neoplasm Metastasis; Antineoplastic Agents; Radium Ra 223 dichloride
• Other Study ID Numbers: 15245; BC1-06 (Other Identifier: Algeta ASA); 2007-006195-11 (EudraCT Number)