Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00004107

Trial Description

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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

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Trial Acronym

ALSYMPCA

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URL of the Trial

[---]*

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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.

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Organizational Data

  •   DRKS00004107
  •   2012/08/31
  •   2008/06/17
  •   no
  •   [---]*
  •   [---]*
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Secondary IDs

  •   NCT00699751  (ClinicalTrials.gov)
  •   15245  (Bayer)
  •   BC1-06 
  •   2007-006195-11 
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Health Condition or Problem studied

  •   Hormone Refractory Prostate Cancer
  •   Bone Metastases
  •   C61 -  Malignant neoplasm of prostate
  •   C79.5 -  Secondary malignant neoplasm of bone and bone marrow
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Interventions/Observational Groups

  •   Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
  •   Drug: Placebo
  •   Drug: Best standard of care (BSoC)
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, caregiver, investigator/therapist, assessor
  •   Placebo
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

- Overall Survival; time frame: 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); Overall survival was defined as the time from date of randomization to the date of death.

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Secondary Outcome

- Time to Total Alkaline Phosphatase (ALP) Progression; time frame: From randomization to first ALP progression until approximately 3 years after start of enrollment; 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; 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); 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; 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; 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; 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 Change 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); 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 Decrease From Baseline in Total ALP During the 24 Week Treatment; time frame: From baseline 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.
- Time to Prostate Specific Antigen (PSA) Progression; time frame: From randomization to first PSA progression until approximately 3 years after start of enrollment; 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; 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); 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; 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; 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); 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); 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 approximately 3 years after start of enrollment; 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 approximately 3 years after start of enrollment; 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 approximately 3 years after start of enrollment; 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 approximately 3 years after start of enrollment; 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 approximately 3 years after start of enrollment; 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 approximately 3 years after start of enrollment; 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 approximately 3 years after start of enrollment; 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 approximately 3 years after start of enrollment; 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.

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Countries of Recruitment

  •   United States
  •   Australia
  •   Belgium
  •   Brazil
  •   Canada
  •   Czech Republic
  •   France
  •   Germany
  •   Hong Kong
  •   Israel
  •   Italy
  •   Netherlands
  •   Norway
  •   Poland
  •   Singapore
  •   Slovakia
  •   Spain
  •   Sweden
  •   United Kingdom
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Locations of Recruitment

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Recruitment

  •   [---]*
  •   2008/06/30
  •   900
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Male
  •   18   Years
  •   no maximum age
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Additional 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

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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

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Bayer
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    •   [---]*
    •   [---]*
    •   [---]*
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    • The Royal Marsden Hospital, UK
    • Christopher Parker, MD 
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    •   [---]*
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  • start of 1:1-Block address public-contact
    • The Royal Marsden Hospital, UK
    • Christopher Parker, MD 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    •   [---]*
    •   [---]*
    •   [---]*
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
    •   [---]*
    •   [---]*
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Status

  •   Recruiting complete, follow-up complete
  •   2014/02/01
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Trial Publications, Results and other Documents

  •   Click here and search for drug information provided by the FDA.
  •   Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.
  •   Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså 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, Franzén L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland ØS, 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.; 23863050
  •   Click here to find results for studies related to Bayer Healthcare products.
  •   Click here to find information about studies related to Bayer Healthcare products conducted in Europe.
  •   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.; 25439694
  •   Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså 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 ØS, 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.; 24836273
  •   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.; 25840395
  •   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. Review.; 25832684
  •   1.5-Year post-treatment follow-up of radium-223 dichloride (Ra-223) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase 3 ALSYMPCA Study 9. Clin Adv Hematol Oncol. 2014 Apr;12(4 Suppl 11):9-10.; 24870258
  •   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. Review.; 24857093
  •   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. Review.; 24775727
  •   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. Review.; 24610703
  •   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. Review.; 24052017
  •   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.; 23977665
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  •   4
  •   2016/01/14


* This entry means the parameter is not applicable or has not been set.