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
  Purpose

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.


Condition Intervention Phase
Hormone Refractory Prostate Cancer
Bone Metastases
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Drug: Placebo
Drug: Best standard of care (BSoC)
Phase 3

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
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from date of randomization to the date of death.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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

  • Percentage of Participants With Total ALP Response at Week 12 [ Time Frame: At Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Total ALP Normalization at Week 12 [ Time Frame: At Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in Total ALP at Week 12 [ Time Frame: At Baseline and Week 12 ] [ Designated as safety issue: No ]
    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

  • Maximum Percentage Decrease From Baseline in Total ALP up to Week 12 [ Time Frame: From baseline to Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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

  • Maximum Percentage Change From Baseline in Total ALP During the 24 Week Treatment [ Time Frame: From baseline During the 24 Week Treatment ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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

  • Percentage of Participants With PSA Response at Week 12 [ Time Frame: At Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percentage Change From Baseline in PSA at Week 12 [ Time Frame: At Baseline and Week 12 ] [ Designated as safety issue: No ]
    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

  • Maximum Percentage Decrease From Baseline in PSA up to Week 12 [ Time Frame: From baseline up to Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 0. [ Time Frame: Week 0 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 8. [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 16. [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Week 24. [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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').

  • 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 ] [ Designated as safety issue: No ]
    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').

  • 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) ] [ Designated as safety issue: No ]
    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').


Enrollment: 921
Study Start Date: June 2008
Study Completion Date: February 2014
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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: Placebo
Isotonic saline 6 IV administrations separated by 4 weeks intervals.
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.

Detailed Description:

The aim of the study was to compare, in patients with symptomatic 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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00699751

  Show 135 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Chair: Christopher Parker, MD The Royal Marsden Hospital, UK
  More Information

Additional Information:
Publications:
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

Keywords provided by Bayer:
Hormone Refractory Prostate Cancer
Bone Metastases
Radium-223

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Prostatic Neoplasms
Bone Neoplasms
Bone Marrow Diseases
Neoplastic Processes
Neoplasms
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Succinylcholine
Hormones
Radium Ra 223 dichloride
Neuromuscular Depolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014