Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Randomized Study Comparing Docetaxel Plus Dasatinib to Docetaxel Plus Placebo in Castration-resistant Prostate Cancer (READY)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00744497
First received: August 29, 2008
Last updated: August 23, 2016
Last verified: August 2016
Results First Received: November 15, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Prostatic Neoplasms
Interventions: Drug: Placebo
Drug: Dasatinib
Drug: Docetaxel
Drug: Prednisone

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1930 participants enrolled, 1522 randomized to a treatment group (762 dasatinib, 760 placebo). 408 not randomized. Reasons for non-randomization include 7 adverse events, 42 withdrew consent, 6 deaths, 2 lost to follow up, 3 poor/non compliance, 332 no longer met study criteria, 1 administrative reason by sponsor, and 15 non-specified reasons.

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Participant Flow:   Overall Study
    Placebo   Dasatinib
STARTED   760 [1]   762 [1] 
Received Treatment   757   761 
COMPLETED   0   0 
NOT COMPLETED   760   762 
Withdrawal by Subject                21                18 
Death                11                9 
Lost to Follow-up                4                2 
Poor compliance/noncompliance                9                5 
No longer meets study criteria                7                3 
Administrative Reason By Sponsor                25                8 
Disease progression                312                219 
Study drug toxicity                68                141 
Adverse event unrelated to study drug                78                122 
Patient requested to stop study drug                65                80 
Maximum clinical benefit                141                142 
Not defined                19                13 
[1] Randomized



  Baseline Characteristics


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Overall Survival: Time From Randomization to Date of Death   [ Time Frame: From randomization to death or date of last contact (maximum reached: 45 months) ]

Measure Type Primary
Measure Title Overall Survival: Time From Randomization to Date of Death
Measure Description Overall survival is defined as time in months from the randomization date to the date of death due to any cause (in the randomized population). If the patient did not die, survival was censored on the last date he or she was known to be alive.
Time Frame From randomization to death or date of last contact (maximum reached: 45 months)  
Safety Issue No  

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.
All participants who were randomized to receive any treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 760   762 
Overall Survival: Time From Randomization to Date of Death 
[Units: Months]
Median (95% Confidence Interval)
 21.2 
 (20.0 to 23.4) 
 21.5 
 (20.3 to 22.8) 


Statistical Analysis 1 for Overall Survival: Time From Randomization to Date of Death
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.9009
Hazard Ratio (HR) [4] 0.99
95.53% Confidence Interval 0.87 to 1.13
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Confidence intervals for median overall survival calculated using Brookmeyer and Crowley method. Compared survival in arms by 2-sided, alpha=0.0447 level, log-rank test, stratified by bisphosphonate intake (yes/no) and urinary N-telopeptide category (<60 vs ≥60 nmol/mmol creatinine) defined at randomization. Null hypothesis was survival equal in both arms. Power calculations were that ≥858 deaths would lead to ≥90% power at 5% level for rejecting null hypothesis, given true hazard ratio of 0.8.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  An interim analysis on survival was performed and the final test was corrected for multiplicity.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST)   [ Time Frame: At baseline and every 12 weeks thereafter to end of treatment, at end of treatment, and at follow-up (within 42 days of end of dosing) ]

Measure Type Secondary
Measure Title Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST)
Measure Description Objective tumor response rate=the percentage of randomized participants with a best tumor response of partial (PR) or complete response (CR), within 42 days of end of dosing, divided by total number of patients who were evaluable (with at least 1 target lesion at baseline). By RECIST: CR=disappearance of clinical and radiologic evidence of target and nontarget lesions confirmed by another evaluation at least 6 weeks later. PR=a >30% or greater decrease in the sum of longest diameter (LD) of target lesions in reference to the baseline sum LD confirmed by another evaluation at least 6 weeks later. Stable disease=neither sufficient increase to qualify for PD nor shrinkage to qualify for PR, and at least 8 weeks since start of study therapy. Progressive disease=a 20% or greater increase in sum of LD of all target lesions, taking as reference the smallest sum of LD at or following baseline, or unequivocal progression on existing nontarget lesions, or new lesions are present.
Time Frame At baseline and every 12 weeks thereafter to end of treatment, at end of treatment, and at follow-up (within 42 days of end of dosing)  
Safety Issue No  

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.
Participants with at least 1 target lesion at baseline

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 383   381 
Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST) 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 31.85 
 (27.21 to 36.78) 
 30.45 
 (25.86 to 35.34) 


Statistical Analysis 1 for Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST)
Groups [1] All groups
Odds Ratio (OR) [2] 0.935
95% Confidence Interval 0.688 to 1.271
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The odds ratio is presented for experimental to control group.
[2] Other relevant estimation information:
  No text entered.



3.  Secondary:   Time to First Skeletal-related Event (SRE)   [ Time Frame: From day of randomization to date of first SRE or to last SRE assessment, if subsequent cancer therapy begun or no SRE (maximum reached: 42 months) ]

Measure Type Secondary
Measure Title Time to First Skeletal-related Event (SRE)
Measure Description Time to first SRE is defined as the time in months from the date of randomization to the date of first SRE (unless SRE occurred while the patient was undergoing subsequent cancer therapy). Participants with a first SRE while on subsequent cancer therapy, those who died without a reported SRE, and those who did not have an SRE were censored on the date of their last SRE assessment prior to start of subsequent cancer therapy, if any. Participants who had no SRE assessments were censored on the day they were randomized.
Time Frame From day of randomization to date of first SRE or to last SRE assessment, if subsequent cancer therapy begun or no SRE (maximum reached: 42 months)  
Safety Issue No  

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.
All participants who were randomized to receive any treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 760   762 
Time to First Skeletal-related Event (SRE) 
[Units: Months]
Median (95% Confidence Interval)
 31.1 [1] 
 (28.8 to N/A) 
 NA [1] 
[1] NA=Not estimable; insufficient number of participants with events


Statistical Analysis 1 for Time to First Skeletal-related Event (SRE)
Groups [1] All groups
Hazard Ratio (HR) [2] 0.81
95% Confidence Interval 0.64 to 1.02
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The hazard ratio is presented for experimental to control group.
[2] Other relevant estimation information:
  No text entered.



4.  Secondary:   Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline   [ Time Frame: At baseline, prior to each docetaxel infusion (every 3 weeks) to end of treatment, at end of treatment, and at follow-up (within 14 days of end of dosing) ]

Measure Type Secondary
Measure Title Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline
Measure Description The percentage of participants who had an on-study uNTx value confirmed (at least 3 weeks later) within normal limits (or ≥3 and <60 nmol/mmol creatinine, if normal limits were missing) or an on-study uNTx level reduction from baseline of ≥35%, even when on-study uNTx value remained abnormal.
Time Frame At baseline, prior to each docetaxel infusion (every 3 weeks) to end of treatment, at end of treatment, and at follow-up (within 14 days of end of dosing)  
Safety Issue No  

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.
Participants who entered the study with baseline urinary N-telopeptide values higher than the upper limit of normal (ULN), or ≥60 nmol/mmol creatinine, if ULN was missing

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 335   321 
Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 60.60 
 (55.14 to 65.86) 
 66.04 
 (60.58 to 71.21) 


Statistical Analysis 1 for Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline
Groups [1] All groups
Odds Ratio (OR) [2] 1.280
95% Confidence Interval 0.930 to 1.763
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The odds ratio is presented for experimental to control group.
[2] Other relevant estimation information:
  No text entered.



5.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: From day of randomization to disease progression or death (or to last clinical assessment, if subsequent cancer therapy started or no progression or death) (maximum reached: approximately 43 months) ]

Measure Type Secondary
Measure Title Progression-free Survival (PFS)
Measure Description PFS is defined as the time from the randomization date until the date of earliest evidence of disease progression or death, for participants who progressed or died before subsequent cancer therapy. Those who progressed or died while on subsequent cancer therapy and those who did not die or progress were censored at their last radiologic bone scan/imaging, skeletal related-event, or tumor assessment or at measurement of prostate specific antigen levels, whichever occurred last prior to start of subsequent cancer therapy ,if any. Participants with no assessments were censored on the day of randomization.
Time Frame From day of randomization to disease progression or death (or to last clinical assessment, if subsequent cancer therapy started or no progression or death) (maximum reached: approximately 43 months)  
Safety Issue No  

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.
All participants who were randomized to receive any treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 760   762 
Progression-free Survival (PFS) 
[Units: Months]
Median (95% Confidence Interval)
 11.1 
 (10.8 to 11.7) 
 11.8 
 (11.1 to 13.4) 


Statistical Analysis 1 for Progression-free Survival (PFS)
Groups [1] All groups
Hazard Ratio (HR) [2] 0.92
95% Confidence Interval 0.82 to 1.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The hazard ratio is presented for experimental to control group.
[2] Other relevant estimation information:
  No text entered.



6.  Secondary:   Time to Prostate Specific Antigen (PSA) Progression   [ Time Frame: From randomization to date of first PSA measurement leading to confirmed PSA progression (or to last bone scan assessment, if no progression or if cancer therapy started) (maximum reached: 30 months) ]

Measure Type Secondary
Measure Title Time to Prostate Specific Antigen (PSA) Progression
Measure Description PSA progression is defined as the time from randomization to the date of the first PSA level measurement that led to confirmed PSA progression, for participants who had not started subsequent cancer therapy. For participants who did not progress or who progressed on cancer therapy, PSA progression is defined as the time from randomization to the date of the last PSA level measurement before the start of cancer therapy, if any. Participants who had no on-study PSA level measurements were censored on the day they were randomized.
Time Frame From randomization to date of first PSA measurement leading to confirmed PSA progression (or to last bone scan assessment, if no progression or if cancer therapy started) (maximum reached: 30 months)  
Safety Issue No  

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.
All participants who were randomized to receive any treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 760   762 
Time to Prostate Specific Antigen (PSA) Progression 
[Units: Months]
Median (95% Confidence Interval)
 6.9 
 (6.5 to 7.4) 
 7.2 
 (6.6 to 7.9) 


Statistical Analysis 1 for Time to Prostate Specific Antigen (PSA) Progression
Groups [1] All groups
Hazard Ratio (HR) [2] 0.89
95% Confidence Interval 0.79 to 1.01
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The hazard ratio is presented for experimental to control group.
[2] Other relevant estimation information:
  No text entered.



7.  Secondary:   Percentage of Participants With a Reduction in Pain Intensity From Baseline   [ Time Frame: At baseline, prior to each docetaxel infusion (every 3 weeks), at end of treatment, and at follow-up (within 14 days of end of dosing) ]

Measure Type Secondary
Measure Title Percentage of Participants With a Reduction in Pain Intensity From Baseline
Measure Description The percentage of participants with a reduction in pain intensity from baseline was defined as the number of participants who achieved a 30% or more decrease in pain intensity from baseline for at least 2 consecutive pain assessments (at least 14 days apart) within 14 days of end of dosing divided by the number of randomized participants who had a baseline pain intensity of at least 2. Pain intensity was assessed based on question 3 of the brief pain inventory questionnaire.
Time Frame At baseline, prior to each docetaxel infusion (every 3 weeks), at end of treatment, and at follow-up (within 14 days of end of dosing)  
Safety Issue No  

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.
Participants with a baseline pain intensity of 2 or greater

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 467   419 
Percentage of Participants With a Reduction in Pain Intensity From Baseline 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 71.52 
 (67.19 to 75.57) 
 66.59 
 (61.85 to 71.09) 


Statistical Analysis 1 for Percentage of Participants With a Reduction in Pain Intensity From Baseline
Groups [1] All groups
Odds Ratio (OR) [2] 0.791
95% Confidence Interval 0.594 to 1.052
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The odds ratio is presented for of experimental to control group.
[2] Other relevant estimation information:
  No text entered.



8.  Other Pre-specified:   Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths   [ Time Frame: Continuously throughout study to <=30 days after last dose of study drug; included AEs with an onset date >= day 1 and <= last dose date + 30 days ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths
Measure Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug
Time Frame Continuously throughout study to <=30 days after last dose of study drug; included AEs with an onset date >= day 1 and <= last dose date + 30 days  
Safety Issue Yes  

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.
All participants who received treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 757   761 
Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths 
[Units: Participants]
   
All deaths   505   506 
Deaths within 30 days of end of treatment   50   79 
All SAEs   317   381 
Drug-related SAEs   90   150 
All Drug-related AEs   482   553 
Drug-related AEs leading to discontinuation   76   144 

No statistical analysis provided for Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths



9.  Other Pre-specified:   Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest   [ Time Frame: Continuously throughout study to <=30 days after last dose of study drug; included AEs with an onset date >= day 1 and <= last dose date + 30 days ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest
Measure Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. AEs of Special Interest=recognized events in other agents within this drug class or events for which safety data from nonclinical and clinical studies with dasatinib indicate that careful evaluation is warranted. Drug-related=having certain, probable, possible, or missing relationship to study drug. Drug-related AEs of Special Interest are identified by the medical and safety representatives of the sponsor based on MedDRA preferred terms or laboratory data. ANC=absolute neutrophil count.
Time Frame Continuously throughout study to <=30 days after last dose of study drug; included AEs with an onset date >= day 1 and <= last dose date + 30 days  
Safety Issue Yes  

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.
All participants who received treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 757   761 
Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest 
[Units: Participants]
   
Diarrhea   167   229 
Nausea/vomiting   127   170 
Fatigue   216   236 
Myalgias/arthralgias   29   29 
Rash   46   72 
Gastrointestinal tract bleeding   6   14 
Central nervous system bleeding   1   2 
Other hemorrhage   14   24 
Pulmonary arterial hypertension   0   0 
Fluid retention: Superficial edema   77   76 
Fluid retention: Pleural effusion   13   87 
Fluid retention: Other   37   52 

No statistical analysis provided for Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest



10.  Other Pre-specified:   Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology   [ Time Frame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle) and at end of treatment. If docetaxel is discontinued, every other cycle. ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology
Measure Description Abnormalities were graded according to the Common Toxicity Criteria (CTC), version 3.0, of the National Cancer Institute. CTC are graded from 1 (least severe) to 4 (life threatening ). Grade 3 and 4 criteria are defined as follows: Absolute neutrophil count, Grade 3, neutrophils <1.0-0.5*10^9/L; Grade 4, <0.5*10^9/L. Hemoglobin, Grade 3, <4.9-4.0 mmol/L; Grade 4, <4.0 mmol/L. Platelets, Grade 3, <50.0-25.0*10^9/L; Grade 4, <25.0*10^9/L. Leukocytes, Grade 3, <2.0-1.0*10^9/L; Grade 4, <1.0*10^9/L.
Time Frame At baseline, within 3 days prior to each infusion of docetaxel (each cycle) and at end of treatment. If docetaxel is discontinued, every other cycle.  
Safety Issue Yes  

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.
All participants who received treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 757   761 
Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology 
[Units: Participants]
   
Absolute neutrophil count (All grades)   84   161 
Absolute neutrophil count (Grades 3 and 4)   41   46 
Hemoglobin (All grades)   712   720 
Hemoglobin (Grades 3 and 4)   44   59 
Platelets (All grades)   108   100 
Platelets (Grades 3 and 4)   6   3 
Leukocytes (All grades)   128   149 
Leukocytes (Grades 3 and 4)   32   30 

No statistical analysis provided for Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology



11.  Other Pre-specified:   Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes   [ Time Frame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle. ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes
Measure Description ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal. Abnormalities were graded according to the Common Toxicity Criteria (CTC), version 3.0, of the National Cancer Institute. CTC are graded from 1 (least severe) to 4 (life threatening). ALP, ALT, and AST, Grade 3, >5.0-20.0*ULN; Grade 4, >20.0*ULN. Total bilirubin, Grade 3, >3.0–10.0*ULN; Grade 4, >10.0*ULN. Creatinine, Grade 3, >3.0–6.0*ULN; Grade 4, >6.0*ULN. Hypercalcemia(serum calcium, mmol/L), Grade 3, >3.1-3.4; Grade 4, >3.4. Hypocalcemia (serum calcium, mmol/L), Grade 3, <1.75-1.5; Grade 4, <1.5. Hyperkalemia(serum calcium, mmol/L), Grade 3, >6.0-7.0; Grade 4, >7.0. Hypokalemia(serum calcium, mmol/L), Grade 3, <3.0-2.5; Grade 4, <2.5. Hypernatremia (serum calcium, mmol/L), Grade 3, >155-160; Grade 4, >160. Hyponatremia (serum sodium, mmol/L), Grade 3, <130-120; Grade 4, <120. Phosphorus (serum sodium, mmol/L), Grade 3, <0.6-0.3; Grade 4, <0.3.
Time Frame At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle.  
Safety Issue Yes  

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.
All participants who received treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 757   761 
Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes 
[Units: Participants]
   
ALP (All grades)   447   375 
ALP (Grades 3 and 4)   91   68 
ALT (All grades)   186   256 
ALT (Grades 3 and 4)   5   6 
AST (All grades)   212   266 
AST (Grades 3 and 4)   4   5 
Total bilirubin (All grades)   49   41 
Total bilirubin (Grades 3 and 4)   1   3 
Creatinine (All grades)   153   184 
Creatinine (Grades 3 and 4)   3   5 
Hypercalcemia (All grades)   56   34 
Hypercalcemia (Grades 3 and 4)   1   1 
Hypocalcemia (All grades)   308   377 
Hypocalcemia (Grades 3 and 4)   23   25 
Hyperkalemia (All grades)   164   152 
Hyperkalemia (Grades 3 and 4)   11   14 
Hypokalemia (All grades)   107   152 
Hypokalemia (Grades 3 and 4)   6   16 
Hypernatremia (All grades)   93   101 
Hypernatremia (Grades 3 and 4)   0   0 
Hyponatremia (All grades)   230   241 
Hyponatremia (Grades 3 and 4)   36   43 
Phosporus (All grades)   189   257 
Phosphorus (Grades 3 and 4)   43   93 

No statistical analysis provided for Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes



12.  Other Pre-specified:   Number of Participants With Abnormal Results in Urinalysis   [ Time Frame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle. ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Abnormal Results in Urinalysis
Measure Description Abnormal=positive, defined as the presence of >=30 mg/dL of protein; a small, moderate, or large amount of blood; or >0 g/dL glucose in urine. BL=baseline; neg=negative
Time Frame At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle.  
Safety Issue Yes  

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.
All participants who received treatment.

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 757   761 
Number of Participants With Abnormal Results in Urinalysis 
[Units: Participants]
   
Protein, urine: postive   246   336 
Blood, urine: positive   289   307 
Glucose, urine: positive   179   154 

No statistical analysis provided for Number of Participants With Abnormal Results in Urinalysis



13.  Other Pre-specified:   Number of Participants by Maximal On-study Fridericia-corrected QTc Interval   [ Time Frame: At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing ]

Measure Type Other Pre-specified
Measure Title Number of Participants by Maximal On-study Fridericia-corrected QTc Interval
Measure Description QTc interval measured by electrocardiogram (ECG). Although a participant may have had several ECGs, only the longest QTc interval was included.
Time Frame At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing  
Safety Issue Yes  

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.
All participants who received treatment. n=number evaluable

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 757   761 
Number of Participants by Maximal On-study Fridericia-corrected QTc Interval 
[Units: Participants]
   
<450 msecs (n=600, 548)   550   497 
450-500 msecs (n=600, 548)   43   48 
>500 msecs (n=600, 548)   7   3 

No statistical analysis provided for Number of Participants by Maximal On-study Fridericia-corrected QTc Interval



14.  Other Pre-specified:   Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval   [ Time Frame: At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval
Measure Description QTc interval measured by electrocardiogram (ECG). Although a participant may have had several ECGs, only the longest QTc interval was included.
Time Frame At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing  
Safety Issue Yes  

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.
All participants who received treatment. n=number evaluable

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 757   761 
Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval 
[Units: Participants]
   
0 to 30 msecs increase (n=591, 540)   203   199 
>30 to 60 msecs increase (n=591, 540)   52   47 
>60 msecs increase (n=591, 540)   32   26 
Decrease (n=591, 540)   304   268 

No statistical analysis provided for Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval



15.  Other Pre-specified:   Number of Participants With and Without Pericardial Effusion at Baseline and On-study and With Left Ventricular Ejection Fraction (LVEF) <40% and >=40% On-study   [ Time Frame: At baseline, approximately 12 weeks after start of treatment, and thereafter whenever clinically indicated ]

Measure Type Other Pre-specified
Measure Title Number of Participants With and Without Pericardial Effusion at Baseline and On-study and With Left Ventricular Ejection Fraction (LVEF) <40% and >=40% On-study
Measure Description BL=baseline; OS=on-study
Time Frame At baseline, approximately 12 weeks after start of treatment, and thereafter whenever clinically indicated  
Safety Issue Yes  

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.
All participants who were randomized to receive any treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 760   762 
Number of Participants With and Without Pericardial Effusion at Baseline and On-study and With Left Ventricular Ejection Fraction (LVEF) <40% and >=40% On-study 
[Units: Participants]
   
Pericardial effusion at BL/absent OS   3   1 
Pericardial effusion at BL/present OS   0   1 
Pericardial effusion at BL/not reported OS   1   0 
Pericardial effusion absent at BL/ absent OS   584   545 
Pericardial effusion absent at BL/present OS   24   26 
Pericardial effusion absent at BL/not reported OS   132   184 
Pericardial not reported at BL   16   5 
LVEF OS <40%   2   2 
LVEF OS >=40%   607   566 
LVEF not reported OS   151   194 

No statistical analysis provided for Number of Participants With and Without Pericardial Effusion at Baseline and On-study and With Left Ventricular Ejection Fraction (LVEF) <40% and >=40% On-study




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information