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: August 19, 2014
Last verified: August 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
  Hide Baseline Characteristics

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  
Number of Participants  
[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
  Show 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) ]

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) ]

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 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. ]

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 ]
  Hide Outcome Measure 9

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. ]

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 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 ]

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 ]

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 ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
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
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

Other Adverse Events
    Dasatinib     Placebo  
Total, other (not including serious) adverse events      
# participants affected / at risk     714/761     698/757  
Blood and lymphatic system disorders      
Neutropenia † 1    
# participants affected / at risk     79/761 (10.38%)     67/757 (8.85%)  
Anaemia † 1    
# participants affected / at risk     214/761 (28.12%)     141/757 (18.63%)  
Eye disorders      
Lacrimation increased † 1    
# participants affected / at risk     48/761 (6.31%)     86/757 (11.36%)  
Gastrointestinal disorders      
Constipation † 1    
# participants affected / at risk     152/761 (19.97%)     188/757 (24.83%)  
Stomatitis † 1    
# participants affected / at risk     47/761 (6.18%)     47/757 (6.21%)  
Dyspepsia † 1    
# participants affected / at risk     50/761 (6.57%)     59/757 (7.79%)  
Nausea † 1    
# participants affected / at risk     283/761 (37.19%)     227/757 (29.99%)  
Abdominal pain † 1    
# participants affected / at risk     65/761 (8.54%)     66/757 (8.72%)  
Diarrhoea † 1    
# participants affected / at risk     411/761 (54.01%)     312/757 (41.22%)  
Vomiting † 1    
# participants affected / at risk     161/761 (21.16%)     116/757 (15.32%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     49/761 (6.44%)     33/757 (4.36%)  
Pyrexia † 1    
# participants affected / at risk     132/761 (17.35%)     70/757 (9.25%)  
Mucosal inflammation † 1    
# participants affected / at risk     70/761 (9.20%)     52/757 (6.87%)  
Oedema † 1    
# participants affected / at risk     35/761 (4.60%)     45/757 (5.94%)  
Asthenia † 1    
# participants affected / at risk     163/761 (21.42%)     142/757 (18.76%)  
Fatigue † 1    
# participants affected / at risk     331/761 (43.50%)     327/757 (43.20%)  
Oedema peripheral † 1    
# participants affected / at risk     169/761 (22.21%)     216/757 (28.53%)  
Pain † 1    
# participants affected / at risk     47/761 (6.18%)     60/757 (7.93%)  
Infections and infestations      
Urinary tract infection † 1    
# participants affected / at risk     72/761 (9.46%)     67/757 (8.85%)  
Investigations      
Weight increased † 1    
# participants affected / at risk     36/761 (4.73%)     64/757 (8.45%)  
Weight decreased † 1    
# participants affected / at risk     120/761 (15.77%)     76/757 (10.04%)  
Haemoglobin decreased † 1    
# participants affected / at risk     49/761 (6.44%)     27/757 (3.57%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     205/761 (26.94%)     150/757 (19.82%)  
Dehydration † 1    
# participants affected / at risk     42/761 (5.52%)     23/757 (3.04%)  
Hypocalcaemia † 1    
# participants affected / at risk     40/761 (5.26%)     24/757 (3.17%)  
Hyperglycaemia † 1    
# participants affected / at risk     41/761 (5.39%)     55/757 (7.27%)  
Musculoskeletal and connective tissue disorders      
Back pain † 1    
# participants affected / at risk     145/761 (19.05%)     191/757 (25.23%)  
Musculoskeletal pain † 1    
# participants affected / at risk     60/761 (7.88%)     53/757 (7.00%)  
Muscle spasms † 1    
# participants affected / at risk     15/761 (1.97%)     41/757 (5.42%)  
Myalgia † 1    
# participants affected / at risk     49/761 (6.44%)     54/757 (7.13%)  
Arthralgia † 1    
# participants affected / at risk     102/761 (13.40%)     122/757 (16.12%)  
Muscular weakness † 1    
# participants affected / at risk     37/761 (4.86%)     51/757 (6.74%)  
Bone pain † 1    
# participants affected / at risk     57/761 (7.49%)     68/757 (8.98%)  
Pain in extremity † 1    
# participants affected / at risk     113/761 (14.85%)     128/757 (16.91%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     34/761 (4.47%)     38/757 (5.02%)  
Nervous system disorders      
Headache † 1    
# participants affected / at risk     82/761 (10.78%)     64/757 (8.45%)  
Paraesthesia † 1    
# participants affected / at risk     42/761 (5.52%)     59/757 (7.79%)  
Dizziness † 1    
# participants affected / at risk     62/761 (8.15%)     60/757 (7.93%)  
Dysgeusia † 1    
# participants affected / at risk     165/761 (21.68%)     147/757 (19.42%)  
Neuropathy peripheral † 1    
# participants affected / at risk     83/761 (10.91%)     110/757 (14.53%)  
Peripheral sensory neuropathy † 1    
# participants affected / at risk     98/761 (12.88%)     105/757 (13.87%)  
Psychiatric disorders      
Insomnia † 1    
# participants affected / at risk     75/761 (9.86%)     94/757 (12.42%)  
Renal and urinary disorders      
Haematuria † 1    
# participants affected / at risk     44/761 (5.78%)     44/757 (5.81%)  
Respiratory, thoracic and mediastinal disorders      
Dyspnoea † 1    
# participants affected / at risk     153/761 (20.11%)     125/757 (16.51%)  
Pleural effusion † 1    
# participants affected / at risk     112/761 (14.72%)     28/757 (3.70%)  
Epistaxis † 1    
# participants affected / at risk     33/761 (4.34%)     41/757 (5.42%)  
Cough † 1    
# participants affected / at risk     135/761 (17.74%)     112/757 (14.80%)  
Skin and subcutaneous tissue disorders      
Nail disorder † 1    
# participants affected / at risk     79/761 (10.38%)     119/757 (15.72%)  
Dry skin † 1    
# participants affected / at risk     54/761 (7.10%)     46/757 (6.08%)  
Alopecia † 1    
# participants affected / at risk     311/761 (40.87%)     325/757 (42.93%)  
Rash † 1    
# participants affected / at risk     105/761 (13.80%)     75/757 (9.91%)  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     21/761 (2.76%)     42/757 (5.55%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 15.0



  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