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A Study of Alpharadin With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer (CRPC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01106352
First received: April 16, 2010
Last updated: November 11, 2016
Last verified: November 2016
Results First Received: June 14, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Bone Metastases
Castration-Resistant Prostate Cancer
Interventions: Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Drug: Docetaxel

  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
Study was conducted at seven study centers in United States and one study center in France, between 23 July 2010 (first subject first visit) and 16 June 2015 (last subject last visit).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 70 subjects were enrolled in the study. Of these 17 were in the dose escalation cohort in three dose groups of radium-223 and docetaxel. The remaining 53 subjects were in expanded safety cohort, of them 46 were dosed; 33 received a combination of radium-223 dichloride plus docetaxel and 13 subjects received docetaxel alone.

Reporting Groups
  Description
Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation Subjects received two intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 – Safety Cohort Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
Docetaxel 75 mg/m^2 – Safety Cohort Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Participant Flow:   Overall Study
    Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation   Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation   Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation   Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 – Safety Cohort   Docetaxel 75 mg/m^2 – Safety Cohort
STARTED   7   3   7   36   17 
Started Dose Escalation   7 [1]   3 [1]   7 [1]   0   0 
Completed Dose Escalation   6   3   5   0   0 
Started Safety Cohort   0   0   0   36   17 
Treated Safety Cohort   0   0   0   33 [1]   13 [1] 
Completed Safety Cohort   0   0   0   23   9 
COMPLETED   6   3   5   23 [2]   9 [2] 
NOT COMPLETED   1   0   2   13   8 
Subjects untreated                0                0                0                3                4 
Sponsor Decision                1                0                0                0                0 
Too ill to come in for the visit                0                0                1                0                0 
Lost to Follow-up                0                0                0                0                1 
Death                0                0                1                3                1 
Disease progression                0                0                0                1                0 
Withdrawal by Subject                0                0                0                3                2 
Went on hospice                0                0                0                1                0 
Subject entered hospice                0                0                0                1                0 
Home hospice since July 2013                0                0                0                1                0 
[1] Number of subjects for safety analysis set.
[2] This group is only applicable for Safety cohort 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
Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation Subjects received two intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 – Safety Cohort Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
Docetaxel 75 mg/m^2 – Safety Cohort Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.
Total Total of all reporting groups

Baseline Measures
   Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation   Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation   Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation   Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 – Safety Cohort   Docetaxel 75 mg/m^2 – Safety Cohort   Total 
Overall Participants Analyzed 
[Units: Participants]
 7   3   7   36   17   70 
Age, Customized 
[Units: Participants]
           
<18 years   0   0   0   0   0   0 
Between 18 and 65 years   2   2   3   11   7   25 
>65 years   5   1   4   25   10   45 
Gender 
[Units: Participants]
Count of Participants
           
Female      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Male      7 100.0%      3 100.0%      7 100.0%      36 100.0%      17 100.0%      70 100.0% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects With Dose-Limiting Toxicities – Dose Escalation Part   [ Time Frame: From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part ]

2.  Primary:   Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4   [ Time Frame: From start of study treatment to 6 weeks after study treatment (that is maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) and 8 weeks for serious AEs ]

3.  Primary:   Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period   [ Time Frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort) ]

4.  Primary:   Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period   [ Time Frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort) ]

5.  Primary:   Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period   [ Time Frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort) ]

6.  Primary:   Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period   [ Time Frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort) ]

7.  Primary:   Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period   [ Time Frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort) ]

8.  Primary:   Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period   [ Time Frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort) ]

9.  Primary:   Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period   [ Time Frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) ]

10.  Primary:   Changes From Baseline in Respiratory Rate During the Treatment Period   [ Time Frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) ]

11.  Primary:   Changes From Baseline in Heart Rate During the Treatment Period   [ Time Frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) ]

12.  Primary:   Changes From Baseline in Weight During the Treatment Period   [ Time Frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) ]

13.  Primary:   Number of Subjects With Physical Examination During the Treatment Period   [ Time Frame: From start of study treatment to 6 weeks after study treatment (i.e., maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) ]

14.  Primary:   Number of Subjects With Signs of Long-Term Radiation Toxicity   [ Time Frame: From start of study treatment upto 12 months ]

15.  Other Pre-specified:   Exploratory Efficacy: Weighted Mean Area Under the Curve for Bone Turnover Biomarkers   [ Time Frame: From start of study treatment to 6 weeks after study treatment (maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) ]

16.  Other Pre-specified:   Exploratory Efficacy: Time to Prostate-specific Antigen (PSA) Progression   [ Time Frame: 12 months ]

17.  Other Pre-specified:   Exploratory Efficacy: Percent Change From Baseline in Circulating Tumor Cells at Day 85   [ Time Frame: Baseline, Day 85, expanded safety cohort ]

18.  Other Pre-specified:   Exploratory Efficacy: Time to Clinical or Radiographic Progression   [ Time Frame: From start of study treatment to 12 months, at every 12 weeks ]

19.  Other Pre-specified:   Progression Free Survival (PFS) End Point   [ Time Frame: From start of study treatment to 12 months, at every 12 weeks ]

20.  Other Pre-specified:   Overall Survival Rate   [ Time Frame: 12 months ]

21.  Other Pre-specified:   Number of Subjects Who Responded to Interactive Voice Response System (IVRS) Pain   [ Time Frame: From start of study treatment until 12 months ]


  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
The radium 223 dichloride treatment was calculated as 50 kBq per NIST 2010, and would be approximately 55 kBq per NIST 2015 standard. Pharmacokinetic endpoint was deleted as no PK variables were evaluated in the study.


  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: Bayer
e-mail: Clinical-Trial-Disclosure@bayer.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01106352     History of Changes
Other Study ID Numbers: 15469
BC1-10 ( Other Identifier: Algeta ASA )
2011-000822-31 ( EudraCT Number )
Study First Received: April 16, 2010
Results First Received: June 14, 2016
Last Updated: November 11, 2016