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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
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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
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
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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.
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
Total Total of all reporting groups

Baseline Measures
   Placebo   Dasatinib   Total 
Overall Participants Analyzed 
[Units: Participants]
 760   762   1522 
Age, Customized 
[Units: Participants]
     
Younger than 65 years   263   251   514 
65 to younger than 75 years   323   333   656 
75 years or older   174   178   352 
Gender 
[Units: Participants]
     
Female   0   0   0 
Male   760   762   1522 
Race/Ethnicity, Customized 
[Units: Participants]
     
Asian   56   55   111 
Native Hawaiian or Other Pacific Islander   1   1   2 
Black or African American   34   23   57 
White   645   656   1301 
Other   24   27   51 
Type of metastatic disease 
[Units: Participants]
     
Bone disease only   286   307   593 
Visceral/nodal disease only   73   80   153 
Both bone and visceral/nodal disease   399   373   772 
No evidence of metastatic disease   2   2   4 


  Outcome Measures
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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) ]

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) ]

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) ]

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) ]
  Hide Outcome Measure 4

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) ]

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) ]

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) ]

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 ]

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 ]

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. ]
  Hide Outcome Measure 10

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. ]

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. ]

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 ]

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 ]

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 ]


  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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