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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00744497
First received: August 29, 2008
Last updated: September 25, 2014
Last verified: September 2014
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
A total of 1930 participants were enrolled, and 1522 were randomized to a treatment group; 1518 received at least 1 dose of dasatinib (761) or placebo (757).

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     43 [2]   39 [2]
NOT COMPLETED     717     723  
Withdrawal by Subject                 21                 17  
Death                 11                 7  
Lost to Follow-up                 4                 2  
Poor compliance/noncompliance                 9                 4  
No longer meets study criteria                 7                 3  
Disease progression                 307                 208  
Study drug toxicity                 68                 140  
Adverse event unrelated to study drug                 77                 122  
Patient requested to stop study drug                 64                 72  
Maximum clinical benefit                 141                 138  
Other                 8                 10  
[1] Randomized
[2] Remained on study drug



  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  
Number of 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% Confidence Interval ( 0.87 to 1.13 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Confidence intervals calculated using Brookmeyer and Crowley method. Analysis compared survival in arms by 2-sided, alpha=0.05 level, log-rank test, stratified by bisphosphonate intake (yes/no) and urinary N-telopeptide category (<60 vs ≥60 nmol/mmol creatinine) as defined at randomization. Null hypothesis was that survival was equal in both arms. Power calculations indicated that ≥858 deaths would lead to ≥90% power at 5% level for rejecting null hypothesis, given a 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. Final P-value was adjusted using an alpha spending function.
[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  
Number of 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  
Number of Participants Analyzed  
[units: participants]
  760     762  
Time to First Skeletal-related Event (SRE)  
[units: Months]
Median ( 95% Confidence Interval )
  31.1  
  ( 28.8 to NA ) [1]
  NA  
  ( NA to NA ) [1]
[1] Not estimable, due to the low percentage of participants experiencing skeletal-related 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  
Number of 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  
Number of 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  
Number of 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 of 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  
Number of 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 Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Drug-related AEs Leading to Discontinuation   [ Time Frame: Continuously throughout study to >=30 days after last dose of study drug until resolution of drug-related toxicity, or when toxicity was deemed irreversible, whichever shorter. ]

Measure Type Other Pre-specified
Measure Title Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Drug-related AEs Leading to Discontinuation
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 until resolution of drug-related toxicity, or when toxicity was deemed irreversible, whichever shorter.  
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  
Number of Participants Analyzed  
[units: participants]
  757     761  
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Drug-related AEs Leading to Discontinuation  
[units: Participants]
   
All deaths     461     451  
Deaths on or within 30 days of treatment     49     77  
All SAEs     317     376  
Drug-related SAEs     90     148  
AEs leading to discontinuation     186     293  
Drug-related AEs leading to discontinuation     75     143  

No statistical analysis provided for Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Drug-related AEs Leading to Discontinuation



9.  Other Pre-specified:   Number of Participants With Adverse Events (AEs) of Special Interest   [ Time Frame: Continuously throughout study to >=30 days after last dose of study drug until resolution of drug-related toxicity, or when toxicity was deemed irreversible, whichever was shorter ]

Measure Type Other Pre-specified
Measure Title Number of Participants With 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. 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 until resolution of drug-related toxicity, or when toxicity was deemed irreversible, whichever was shorter  
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  
Number of Participants Analyzed  
[units: participants]
  757     761  
Number of Participants With Adverse Events (AEs) of Special Interest  
[units: Participants]
   
Myelosuppression: Hemoglobin (n=746, 739)     712     720  
Myelosuppression: White blood cells (n=746, 738)     128     149  
Myelosuppression: ANC (n=745, 737)     84     161  
Myelosuppression: Platelets (n=746, 738)     108     100  
Hypocalcemia (n=739, 719)     308     377  
Hypophosphotemia (n=733, 720)     189     257  
Hypmagnesemia (n=734, 721)     108     98  
Diarrhea     314     426  
Nausea/vomiting     268     323  
Fatigue     330     338  
Myalgias/arthralgias     170     142  
Rash     115     147  
Gastrointestinal tract bleeding     39     72  
Central nervous system bleeding     1     4  
Other hemorrhage     134     120  
Pulmonary arterial hypertension     0     0  
Fluid retention: Superficial edema     237     184  
Fluid retention: Pleural effusion     30     118  
Fluid retention: Other     85     98  

No statistical analysis provided for Number of Participants With 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  
Number of 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  
Number of 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  
Number of 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 by Electrocardiogram   [ 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 by Electrocardiogram
Measure Description No text entered.
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  
Number of Participants Analyzed  
[units: participants]
  757     761  
Number of Participants by Maximal On-study Fridericia-corrected QTc Interval by Electrocardiogram  
[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 by Electrocardiogram



14.  Other Pre-specified:   Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval by Electrocardiogram   [ 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 by Electrocardiogram
Measure Description No text entered.
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  
Number of Participants Analyzed  
[units: participants]
  757     761  
Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval by Electrocardiogram  
[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 by Electrocardiogram



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 by Echocardiogram   [ 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 by Echocardiogram
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  
Number of 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 by Echocardiogram  
[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 by Echocardiogram




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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