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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00699751
First received: June 17, 2008
Last updated: April 8, 2014
Last verified: April 2014
Results First Received: June 29, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Hormone Refractory Prostate Cancer
Bone Metastases
Interventions: Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Drug: Placebo
Drug: Best standard of care (BSoC)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects with progressive symptomatic hormone refractory prostate cancer (HRPC), with at least 2 skeletal metastases on bone scan and no known visceral metastases, could participate in the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were to be randomized in a 2:1, a total of 921 subjects were enrolled in the study and were randomized to receive either Alpharadin or placebo study treatment, which resulted in 614 subjects enrolled in the Alpharadin group and 307 enrolled in the placebo group.

Reporting Groups
  Description
A) Radium-223 Dichloride (Xofigo, BAY88-8223) Participants received BSoC plus radium-223 50 kilo Becquerel (kBq)/kg body weight (b.w.) for 6 intravenous (IV) administrations separated by 4 weeks intervals. Note: safety data of participants in the arm presented here are reported in Reporting Group 1 (RG 1) in the safety section.
B1) Placebo Participants received BSoC plus isotonic saline for 6 IV administrations separated by 4 weeks intervals. Note: safety data of participants in the arm presented here are reported in RG 2 in the safety section.
B2) Placebo Randomized, Then Switched to Radium-223 Dichloride Participants received BSoC plus isotonic saline for 6 IV administrations separated by 4 weeks intervals from randomization to data cut-off date of 15 Jul 2011; Participants received radium-223 50 kilo Becquerel (kBq)/kg body weight (b.w.) for 6 intravenous (IV) administrations separated by 4 weeks intervals from 15 Jul 2011 to end of study. Note: safety data of participants in the arm presented here are reported in RG 2 and RG 3 in the safety section.

Participant Flow:   Overall Study
    A) Radium-223 Dichloride (Xofigo, BAY88-8223)     B1) Placebo     B2) Placebo Randomized, Then Switched to Radium-223 Dichloride  
STARTED     614     281     26  
Participants Received Treatment     600 [1]   276 [2]   25 [3]
Completed All 6 Injections     388 [4]   129 [5]   16  
Entered Follow-up Period     406     155 [6]   13  
COMPLETED     16     4     0  
NOT COMPLETED     598     277     26  
[1] Subjects at Risk/Safety Population - in RG1 (RG = Reporting Group for Safety Data)
[2] Subjects at Risk/Safety Population - partly in RG2
[3] Subjects at Risk/Safety Population - partly in RG2 and RG3
[4] 6 participants were not counted due to Treatment Completion Page not yet received
[5] 2 participants were not counted due to Treatment Completion Page not yet received
[6] Participants were not required to complete all 6 injections to enter to 3-year follow-up period.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Radium-223 Dichloride (Xofigo, BAY88-8223) Radium-223 50 kilo Becquerel (kBq)/kg body weight (b.w.) for 6 intravenous (IV) administrations separated by 4 weeks intervals plus BSoC.
Placebo Isotonic saline for 6 IV administrations separated by 4 weeks intervals plus BSoC.
Total Total of all reporting groups

Baseline Measures
    Radium-223 Dichloride (Xofigo, BAY88-8223)     Placebo     Total  
Number of Participants  
[units: participants]
  614     307     921  
Age  
[units: Years]
Mean ± Standard Deviation
  70.2  ± 8.10     70.8  ± 7.87     70.4  ± 8.03  
Gender  
[units: Participants]
     
Female     0     0     0  
Male     614     307     921  
Total Alkaline Phosphatase (ALP) [1]
[units: Participants]
     
< 220 U/L     348     169     517  
≥ 220 U/L     266     138     404  
Current use of bisphosphonates [2]
[units: Participants]
     
Yes     250     124     374  
No     364     183     547  
Any prior use of docetaxel  
[units: Participants]
     
Yes     352     174     526  
No     262     133     395  
[1] The total amount of ALP in the blood was determined at baseline.
[2] Subjects may have been on bisphosphonate therapy during the study.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Overall Survival   [ Time Frame: From randomization to death due to any cause until the data cut-off date approximately 3 years after start of enrollment ]

2.  Secondary:   Time to Total Alkaline Phosphatase (ALP) Progression   [ Time Frame: From randomization to first ALP progression until the data cut-off date approximately 3 years after start of enrollment ]

3.  Secondary:   Percentage of Participants With Total ALP Response at Week 12   [ Time Frame: At Baseline and Week 12 ]

4.  Secondary:   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)   [ Time Frame: At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase) ]

5.  Secondary:   Percentage of Participants With Total ALP Normalization at Week 12   [ Time Frame: At Baseline and Week 12 ]

6.  Secondary:   Percentage Change From Baseline in Total ALP at Week 12   [ Time Frame: At Baseline and Week 12 ]

7.  Secondary:   Maximum Percentage Decrease From Baseline in Total ALP up to Week 12   [ Time Frame: From baseline to Week 12 ]

8.  Secondary:   Percentage Decrease From Baseline in Total ALP at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)   [ Time Frame: At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase) ]

9.  Secondary:   Maximum Percentage Change From Baseline in Total ALP During the 24 Week Treatment   [ Time Frame: From baseline During the 24 Week Treatment ]

10.  Secondary:   Time to Prostate Specific Antigen (PSA) Progression   [ Time Frame: From randomization to first PSA progression until the data cut-off date approximately 3 years after start of enrollment ]

11.  Secondary:   Percentage of Participants With PSA Response at Week 12   [ Time Frame: At Baseline and Week 12 ]

12.  Secondary:   Percentage of Participants With PSA Response at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)   [ Time Frame: At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase) ]

13.  Secondary:   Percentage Change From Baseline in PSA at Week 12   [ Time Frame: At Baseline and Week 12 ]

14.  Secondary:   Maximum Percentage Decrease From Baseline in PSA up to Week 12   [ Time Frame: From baseline up to Week 12 ]

15.  Secondary:   Percentage Change From Baseline in PSA at EOT (Week 24 or at the Time the Patient Dies or Discontinues Treatment Phase)   [ Time Frame: At Baseline and End of Treatment (Week 24 or at the time the patient dies or discontinues treatment phase) ]

16.  Secondary:   Maximum Percentage Decrease From Baseline in PSA Response During the 24 Week Treatment Period   [ Time Frame: From baseline to End of Treatment (Week 24; 4 weeks post last injection) ]

17.  Secondary:   Time to First Skeletal Related Event (SRE)   [ Time Frame: From randomization to first first SRE until the data cut-off date approximately 3 years after start of enrollment ]

18.  Secondary:   Time to Occurrence of First Use of External Beam Radiation Therapy (EBRT) to Relieve Skeletal Symptoms   [ Time Frame: From randomization to first EBRT until the data cut-off date approximately 3 years after start of enrollment ]

19.  Secondary:   Time to Occurrence of First Use of Radioisotopes to Relieve Skeletal Symptoms   [ Time Frame: From randomization to first use of radioisotopes until the data cut-off date approximately 3 years after start of enrollment ]

20.  Secondary:   Time to Occurrence of First New Symptomatic Pathological Bone Fractures, Vertebral and Non-vertebral   [ Time Frame: From randomization to occurrence of first new symptomatic pathological bone fractures until the data cut-off date approximately 3 years after start of enrollment ]

21.  Secondary:   Time to Occurrence of First Tumor Related Orthopedic Surgical Intervention   [ Time Frame: From randomization to occurrence of first tumor related orthopedic surgical intervention until the data cut-off date approximately 3 years after start of enrollment ]

22.  Secondary:   Time to Occurrence of First Spinal Cord Compression   [ Time Frame: From randomization to first spinal cord compression until the data cut-off date approximately 3 years after start of enrollment ]

23.  Secondary:   Time to Occurrence of First Start of Any Other Anti-cancer Treatment   [ Time Frame: From randomization to first start of any other anti-cancer treatment until the data cut-off date approximately 3 years after start of enrollment ]

24.  Secondary:   Time to Occurrence of First Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least 2 Points From Baseline   [ Time Frame: From randomization to first deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) until the data cut-off date approximately 3 years after start of enrollment ]

25.  Other Pre-specified:   Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 0.   [ Time Frame: Week 0 ]

26.  Other Pre-specified:   Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 8.   [ Time Frame: Week 8 ]

27.  Other Pre-specified:   Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 16.   [ Time Frame: Week 16 ]

28.  Other Pre-specified:   Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 24.   [ Time Frame: Week 24 ]

29.  Other Pre-specified:   Absolute Scores for Functional Assessment of Cancer Therapy – Prostate (FACT-P) Trial Outcome Index (TOI)   [ Time Frame: Baseline, Week 16, Week 24, and Follow-up Visit 2 (Week 42) ]

30.  Other Pre-specified:   Changes From Baseline for FACT-P Trial Outcome Index (TOI) at Week 16, Week 24, and Follow-up Visit 2 (Week 42)   [ Time Frame: Baseline, Week 16, Week 24, and Follow-up Visit 2 (Week 42) ]

31.  Other Pre-specified:   Absolute Scores for Physical Well Being, Social/Family Well Being, Emotional Well Being, Functional Well Being, and the Prostate Cancer Subscale at Week 16   [ Time Frame: At Week 16 ]

32.  Other Pre-specified:   Absolute Scores for Physical Well Being, Social/Family Well Being, Emotional Well Being, Functional Well Being, and the Prostate Cancer Subscale at Week 24   [ Time Frame: At Week 24 ]

33.  Other Pre-specified:   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)   [ Time Frame: At Follow-up Visit 2 (Week 42) ]

34.  Other Pre-specified:   Absolute Scores for FACT-P Total Score at Week 16, Week 24, and Follow-up Visit 2 (Week 42)   [ Time Frame: At Week 16, Week 24, and Follow-up Visit 2 (Week 42) ]

35.  Other Pre-specified:   Change From Baseline for FACT-P Total Score at Week 16, Week 24, and Follow-up Visit 2 (Week 42)   [ Time Frame: Baseline, Week 16, Week 24, and Follow-up Visit 2 (week 42) ]

36.  Other Pre-specified:   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)   [ Time Frame: At Week 16, Week 24, and Follow-up Visit 2 (Week 42) ]

37.  Other Pre-specified:   Change From Baseline for FACT-G Total Score at Week 16, Week 24, and Follow-up Visit 2 (Week 42)   [ Time Frame: Baseline, Week 16, Week 24, and Follow-up Visit 2 (Week 42) ]

38.  Other Pre-specified:   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   [ Time Frame: Week 16 ]

39.  Other Pre-specified:   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   [ Time Frame: Week 24 ]

40.  Other Pre-specified:   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)   [ Time Frame: Follow-up Visit 8 (Week 139) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00699751     History of Changes
Other Study ID Numbers: 15245, BC1-06
Study First Received: June 17, 2008
Results First Received: June 29, 2013
Last Updated: April 8, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Ministry of Social Affairs, Public Health and the Environment
Brazil: Ministry of Health
Canada: Canadian Institutes of Health Research
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
Italy: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Singapore: Health Sciences Authority
Spain: Spanish Agency of Medicines
Slovakia: State Institute for Drug Control
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Israel: Israeli Health Ministry Pharmaceutical Administration
United States: Food and Drug Administration