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

• ClinicalTrials.gov Identifier: NCT00744497
• Recruitment Status: Completed
• First Posted: September 1, 2008
• Results First Posted: February 6, 2014
• Last Update Posted: October 17, 2016
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Prostatic Neoplasms
• Interventions: Drug: Placebo; Drug: Dasatinib; Drug: Docetaxel; Drug: Prednisone
• Enrollment: 1930

Participant Flow

Recruitment Details
Pre-assignment Details	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.

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description	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	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
Period Title: Overall Study
Started	760 [1]	762 [1]
Received Treatment	757	761
Completed	0	0
Not Completed	760	762
Reason Not Completed
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

Arm/Group Title		Placebo	Dasatinib	Total
Arm/Group Description		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	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 of all reporting groups
Overall Number of Baseline Participants		760	762	1522
Baseline Analysis Population Description		All participants who were randomized to receive any treatment
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	760 participants	762 participants	1522 participants
Younger than 65 years		263	251	514
65 to younger than 75 years		323	333	656
75 years or older		174	178	352
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	760 participants	762 participants	1522 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	760 100.0%	762 100.0%	1522 100.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	760 participants	762 participants	1522 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; Measure Type: Number; Unit of measure: Participants	Number Analyzed	760 participants	762 participants	1522 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

1. Primary Outcome

Title	Overall Survival: Time From Randomization to Date of Death
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)

Outcome Measure Data

Analysis Population Description

All participants who were randomized to receive any treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	760	762
Median (95% Confidence Interval); Unit of Measure: Months
	21.2; (20.0 to 23.4)	21.5; (20.3 to 22.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dasatinib
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9009
	Comments	An interim analysis on survival was performed and the final test was corrected for multiplicity.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95.53%; 0.87 to 1.13
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST)
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)

Outcome Measure Data

Analysis Population Description

Participants with at least 1 target lesion at baseline

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	383	381
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	31.85; (27.21 to 36.78)	30.45; (25.86 to 35.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dasatinib
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.935
	Confidence Interval	(2-Sided) 95%; 0.688 to 1.271
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Time to First Skeletal-related Event (SRE)
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)

Outcome Measure Data

Analysis Population Description

All participants who were randomized to receive any treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	760	762
Median (95% Confidence Interval); Unit of Measure: Months
	31.1 [1]; (28.8 to NA)	NA [1]; (NA to NA)

[1]

NA=Not estimable; insufficient number of participants with events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dasatinib
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.02
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline
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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	335	321
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	60.60; (55.14 to 65.86)	66.04; (60.58 to 71.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dasatinib
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.280
	Confidence Interval	(2-Sided) 95%; 0.930 to 1.763
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Progression-free Survival (PFS)
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)

Outcome Measure Data

Analysis Population Description

All participants who were randomized to receive any treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	760	762
Median (95% Confidence Interval); Unit of Measure: Months
	11.1; (10.8 to 11.7)	11.8; (11.1 to 13.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dasatinib
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.05
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Time to Prostate Specific Antigen (PSA) Progression
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)

Outcome Measure Data

Analysis Population Description

All participants who were randomized to receive any treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	760	762
Median (95% Confidence Interval); Unit of Measure: Months
	6.9; (6.5 to 7.4)	7.2; (6.6 to 7.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dasatinib
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.01
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Percentage of Participants With a Reduction in Pain Intensity From Baseline
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)

Outcome Measure Data

Analysis Population Description

Participants with a baseline pain intensity of 2 or greater

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	467	419
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	71.52; (67.19 to 75.57)	66.59; (61.85 to 71.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dasatinib
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.791
	Confidence Interval	(2-Sided) 95%; 0.594 to 1.052
	Estimation Comments	[Not Specified]

8. Other Pre-specified Outcome

Title	Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths
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

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	757	761
Measure Type: Number; Unit of Measure: 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

9. Other Pre-specified Outcome

Title	Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest
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

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	757	761
Measure Type: Number; Unit of Measure: 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

10. Other Pre-specified Outcome

Title	Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology
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.

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	757	761
Measure Type: Number; Unit of Measure: 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

11. Other Pre-specified Outcome

Title	Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes
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.

Outcome Measure Data

Analysis Population Description

All participants who received treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	757	761
Measure Type: Number; Unit of Measure: 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

12. Other Pre-specified Outcome

Title	Number of Participants With Abnormal Results in Urinalysis
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.

Outcome Measure Data

Analysis Population Description

All participants who received treatment.

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	757	761
Measure Type: Number; Unit of Measure: Participants
Protein, urine: postive	246	336
Blood, urine: positive	289	307
Glucose, urine: positive	179	154

13. Other Pre-specified Outcome

Title	Number of Participants by Maximal On-study Fridericia-corrected QTc Interval
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

Outcome Measure Data

Analysis Population Description

All participants who received treatment. n=number evaluable

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	757	761
Measure Type: Number; Unit of Measure: Participants
<450 msecs (n=600, 548)	550	497
450-500 msecs (n=600, 548)	43	48
>500 msecs (n=600, 548)	7	3

14. Other Pre-specified Outcome

Title	Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval
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

Outcome Measure Data

Analysis Population Description

All participants who received treatment. n=number evaluable

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	757	761
Measure Type: Number; Unit of Measure: 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

15. Other Pre-specified Outcome

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
Description	BL=baseline; OS=on-study
Time Frame	At baseline, approximately 12 weeks after start of treatment, and thereafter whenever clinically indicated

Outcome Measure Data

Analysis Population Description

All participants who were randomized to receive any treatment

Arm/Group Title	Placebo	Dasatinib
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	760	762
Measure Type: Number; Unit of Measure: 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

Adverse Events

Time Frame	Day 1 up to 30 days post last dose of study therapy
Adverse Event Reporting Description	Study initiated: October 2008; Study Completion: July 2015
Arm/Group Title	Placebo	Dasatinib
Arm/Group Description	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	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
All-Cause Mortality
	Placebo	Dasatinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Placebo	Dasatinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	317/757 (41.88%)	381/761 (50.07%)
Blood and lymphatic system disorders
Febrile bone marrow aplasia † 1	0/757 (0.00%)	1/761 (0.13%)
Hypochromic anaemia † 1	1/757 (0.13%)	0/761 (0.00%)
Leukopenia † 1	7/757 (0.92%)	9/761 (1.18%)
Anaemia † 1	15/757 (1.98%)	21/761 (2.76%)
Agranulocytosis † 1	1/757 (0.13%)	0/761 (0.00%)
Neutropenia † 1	18/757 (2.38%)	19/761 (2.50%)
Normochromic normocytic anaemia † 1	1/757 (0.13%)	0/761 (0.00%)
Disseminated intravascular coagulation † 1	0/757 (0.00%)	1/761 (0.13%)
Thrombocytopenia † 1	2/757 (0.26%)	1/761 (0.13%)
Febrile neutropenia † 1	27/757 (3.57%)	32/761 (4.20%)
Haemorrhagic anaemia † 1	0/757 (0.00%)	1/761 (0.13%)
Cardiac disorders
Supraventricular tachycardia † 1	2/757 (0.26%)	1/761 (0.13%)
Cardiopulmonary failure † 1	0/757 (0.00%)	1/761 (0.13%)
Sinus node dysfunction † 1	1/757 (0.13%)	0/761 (0.00%)
Acute coronary syndrome † 1	1/757 (0.13%)	1/761 (0.13%)
Coronary artery disease † 1	1/757 (0.13%)	0/761 (0.00%)
Atrial flutter † 1	2/757 (0.26%)	0/761 (0.00%)
Cardiac arrest † 1	1/757 (0.13%)	2/761 (0.26%)
Cardio-respiratory arrest † 1	0/757 (0.00%)	1/761 (0.13%)
Tachycardia † 1	1/757 (0.13%)	1/761 (0.13%)
Acute myocardial infarction † 1	0/757 (0.00%)	3/761 (0.39%)
Cardiac failure † 1	3/757 (0.40%)	1/761 (0.13%)
Myocardial ischaemia † 1	2/757 (0.26%)	2/761 (0.26%)
Pericardial effusion † 1	1/757 (0.13%)	1/761 (0.13%)
Atrial fibrillation † 1	8/757 (1.06%)	8/761 (1.05%)
Atrioventricular block second degree † 1	0/757 (0.00%)	1/761 (0.13%)
Left ventricular dysfunction † 1	0/757 (0.00%)	1/761 (0.13%)
Supraventricular tachyarrhythmia † 1	0/757 (0.00%)	1/761 (0.13%)
Cardiac failure congestive † 1	3/757 (0.40%)	1/761 (0.13%)
Myocardial infarction † 1	1/757 (0.13%)	2/761 (0.26%)
Angina pectoris † 1	1/757 (0.13%)	2/761 (0.26%)
Arrhythmia † 1	0/757 (0.00%)	2/761 (0.26%)
Cardiac disorder † 1	0/757 (0.00%)	1/761 (0.13%)
Congenital, familial and genetic disorders
Hydrocele † 1	1/757 (0.13%)	0/761 (0.00%)
Eye disorders
Maculopathy † 1	1/757 (0.13%)	0/761 (0.00%)
Amaurosis fugax † 1	1/757 (0.13%)	0/761 (0.00%)
Gastrointestinal disorders
Abdominal hernia † 1	1/757 (0.13%)	0/761 (0.00%)
Dyspepsia † 1	1/757 (0.13%)	0/761 (0.00%)
Enterovesical fistula † 1	1/757 (0.13%)	0/761 (0.00%)
Gastric haemorrhage † 1	0/757 (0.00%)	1/761 (0.13%)
Large intestinal obstruction † 1	1/757 (0.13%)	0/761 (0.00%)
Reflux gastritis † 1	1/757 (0.13%)	0/761 (0.00%)
Stomatitis † 1	1/757 (0.13%)	2/761 (0.26%)
Colitis † 1	0/757 (0.00%)	4/761 (0.53%)
Diverticular perforation † 1	1/757 (0.13%)	0/761 (0.00%)
Gastritis erosive † 1	0/757 (0.00%)	1/761 (0.13%)
Melaena † 1	1/757 (0.13%)	2/761 (0.26%)
Mouth ulceration † 1	0/757 (0.00%)	1/761 (0.13%)
Nausea † 1	7/757 (0.92%)	13/761 (1.71%)
Anal fissure † 1	1/757 (0.13%)	0/761 (0.00%)
Anal fistula † 1	0/757 (0.00%)	2/761 (0.26%)
Gastrooesophageal reflux disease † 1	1/757 (0.13%)	0/761 (0.00%)
Intra-abdominal haemorrhage † 1	0/757 (0.00%)	1/761 (0.13%)
Megacolon † 1	0/757 (0.00%)	1/761 (0.13%)
Periodontal disease † 1	0/757 (0.00%)	1/761 (0.13%)
Subileus † 1	1/757 (0.13%)	0/761 (0.00%)
Duodenal ulcer haemorrhage † 1	0/757 (0.00%)	1/761 (0.13%)
Gastric ulcer † 1	3/757 (0.40%)	2/761 (0.26%)
Proctalgia † 1	0/757 (0.00%)	1/761 (0.13%)
Proctitis † 1	0/757 (0.00%)	1/761 (0.13%)
Volvulus † 1	0/757 (0.00%)	1/761 (0.13%)
Abdominal pain † 1	3/757 (0.40%)	6/761 (0.79%)
Abdominal pain upper † 1	3/757 (0.40%)	1/761 (0.13%)
Duodenal ulcer perforation † 1	1/757 (0.13%)	0/761 (0.00%)
Haematochezia † 1	0/757 (0.00%)	1/761 (0.13%)
Intestinal perforation † 1	0/757 (0.00%)	1/761 (0.13%)
Peptic ulcer † 1	0/757 (0.00%)	1/761 (0.13%)
Haematemesis † 1	2/757 (0.26%)	0/761 (0.00%)
Ileus † 1	1/757 (0.13%)	0/761 (0.00%)
Inguinal hernia † 1	1/757 (0.13%)	0/761 (0.00%)
Rectal haemorrhage † 1	5/757 (0.66%)	8/761 (1.05%)
Diarrhoea † 1	10/757 (1.32%)	44/761 (5.78%)
Enteritis † 1	0/757 (0.00%)	1/761 (0.13%)
Gastric ulcer perforation † 1	0/757 (0.00%)	1/761 (0.13%)
Intestinal obstruction † 1	2/757 (0.26%)	1/761 (0.13%)
Vomiting † 1	10/757 (1.32%)	14/761 (1.84%)
Constipation † 1	10/757 (1.32%)	5/761 (0.66%)
Dysphagia † 1	1/757 (0.13%)	1/761 (0.13%)
Gastrointestinal haemorrhage † 1	7/757 (0.92%)	8/761 (1.05%)
Gastrointestinal ulcer † 1	1/757 (0.13%)	0/761 (0.00%)
Lower gastrointestinal haemorrhage † 1	0/757 (0.00%)	2/761 (0.26%)
Oesophagitis † 1	1/757 (0.13%)	0/761 (0.00%)
Toothache † 1	0/757 (0.00%)	1/761 (0.13%)
Upper gastrointestinal haemorrhage † 1	0/757 (0.00%)	3/761 (0.39%)
General disorders
Device occlusion † 1	2/757 (0.26%)	0/761 (0.00%)
Hyperthermia † 1	0/757 (0.00%)	1/761 (0.13%)
Pain † 1	9/757 (1.19%)	7/761 (0.92%)
Peripheral swelling † 1	1/757 (0.13%)	0/761 (0.00%)
Pyrexia † 1	14/757 (1.85%)	29/761 (3.81%)
Death † 1	2/757 (0.26%)	3/761 (0.39%)
Face oedema † 1	0/757 (0.00%)	1/761 (0.13%)
Influenza like illness † 1	0/757 (0.00%)	1/761 (0.13%)
Mucosal inflammation † 1	1/757 (0.13%)	1/761 (0.13%)
Oedema † 1	0/757 (0.00%)	1/761 (0.13%)
Malaise † 1	0/757 (0.00%)	1/761 (0.13%)
Oedema peripheral † 1	3/757 (0.40%)	6/761 (0.79%)
Sudden death † 1	3/757 (0.40%)	0/761 (0.00%)
Fatigue † 1	9/757 (1.19%)	15/761 (1.97%)
Multi-organ failure † 1	1/757 (0.13%)	3/761 (0.39%)
Performance status decreased † 1	0/757 (0.00%)	1/761 (0.13%)
General physical health deterioration † 1	1/757 (0.13%)	4/761 (0.53%)
Chest pain † 1	8/757 (1.06%)	9/761 (1.18%)
Condition aggravated † 1	1/757 (0.13%)	0/761 (0.00%)
Generalised oedema † 1	1/757 (0.13%)	1/761 (0.13%)
Disease progression † 1	0/757 (0.00%)	2/761 (0.26%)
Localised oedema † 1	1/757 (0.13%)	1/761 (0.13%)
Asthenia † 1	7/757 (0.92%)	13/761 (1.71%)
Chills † 1	1/757 (0.13%)	1/761 (0.13%)
Hepatobiliary disorders
Cholecystitis † 1	1/757 (0.13%)	2/761 (0.26%)
Cholecystitis acute † 1	1/757 (0.13%)	0/761 (0.00%)
Cholelithiasis † 1	2/757 (0.26%)	1/761 (0.13%)
Hepatic pain † 1	1/757 (0.13%)	0/761 (0.00%)
Hepatotoxicity † 1	1/757 (0.13%)	0/761 (0.00%)
Immune system disorders
Hypersensitivity † 1	1/757 (0.13%)	3/761 (0.39%)
Anaphylactic reaction † 1	0/757 (0.00%)	1/761 (0.13%)
Drug hypersensitivity † 1	0/757 (0.00%)	2/761 (0.26%)
Infections and infestations
Diverticulitis † 1	3/757 (0.40%)	1/761 (0.13%)
Empyema † 1	1/757 (0.13%)	0/761 (0.00%)
Gastroenteritis † 1	3/757 (0.40%)	3/761 (0.39%)
Scrotal abscess † 1	1/757 (0.13%)	0/761 (0.00%)
Bronchitis † 1	3/757 (0.40%)	1/761 (0.13%)
Cellulitis † 1	3/757 (0.40%)	9/761 (1.18%)
Cystitis † 1	1/757 (0.13%)	1/761 (0.13%)
Oesophageal infection † 1	0/757 (0.00%)	1/761 (0.13%)
Peritonitis † 1	1/757 (0.13%)	1/761 (0.13%)
Pyelonephritis acute † 1	1/757 (0.13%)	0/761 (0.00%)
Tooth infection † 1	1/757 (0.13%)	1/761 (0.13%)
Cellulitis of male external genital organ † 1	0/757 (0.00%)	1/761 (0.13%)
Lower respiratory tract infection † 1	0/757 (0.00%)	5/761 (0.66%)
Endocarditis † 1	0/757 (0.00%)	1/761 (0.13%)
Infection † 1	4/757 (0.53%)	8/761 (1.05%)
Lobar pneumonia † 1	1/757 (0.13%)	1/761 (0.13%)
Lung infection † 1	0/757 (0.00%)	2/761 (0.26%)
Oral candidiasis † 1	1/757 (0.13%)	1/761 (0.13%)
Respiratory tract infection † 1	1/757 (0.13%)	4/761 (0.53%)
Sepsis † 1	6/757 (0.79%)	7/761 (0.92%)
Upper respiratory tract infection † 1	0/757 (0.00%)	1/761 (0.13%)
Urinary tract infection † 1	7/757 (0.92%)	10/761 (1.31%)
Candida infection † 1	0/757 (0.00%)	1/761 (0.13%)
Clostridium difficile colitis † 1	0/757 (0.00%)	1/761 (0.13%)
Gangrene † 1	0/757 (0.00%)	1/761 (0.13%)
Herpes zoster † 1	2/757 (0.26%)	0/761 (0.00%)
Intestinal sepsis † 1	0/757 (0.00%)	1/761 (0.13%)
Neutropenic sepsis † 1	0/757 (0.00%)	2/761 (0.26%)
Balanoposthitis infective † 1	0/757 (0.00%)	1/761 (0.13%)
Device related infection † 1	0/757 (0.00%)	1/761 (0.13%)
Encephalitis † 1	1/757 (0.13%)	0/761 (0.00%)
Enterocolitis bacterial † 1	0/757 (0.00%)	1/761 (0.13%)
Fungal oesophagitis † 1	1/757 (0.13%)	0/761 (0.00%)
Influenza † 1	0/757 (0.00%)	1/761 (0.13%)
Pneumonia † 1	22/757 (2.91%)	33/761 (4.34%)
Septic shock † 1	3/757 (0.40%)	10/761 (1.31%)
Urosepsis † 1	4/757 (0.53%)	1/761 (0.13%)
Abscess intestinal † 1	1/757 (0.13%)	0/761 (0.00%)
Bacteraemia † 1	1/757 (0.13%)	0/761 (0.00%)
Bronchopneumonia † 1	0/757 (0.00%)	1/761 (0.13%)
Gastrointestinal infection † 1	1/757 (0.13%)	3/761 (0.39%)
Pneumonia streptococcal † 1	0/757 (0.00%)	1/761 (0.13%)
Staphylococcal sepsis † 1	0/757 (0.00%)	2/761 (0.26%)
Anal abscess † 1	2/757 (0.26%)	1/761 (0.13%)
Appendicitis † 1	3/757 (0.40%)	1/761 (0.13%)
Clostridium difficile infection † 1	0/757 (0.00%)	1/761 (0.13%)
Device related sepsis † 1	1/757 (0.13%)	0/761 (0.00%)
Erysipelas † 1	0/757 (0.00%)	1/761 (0.13%)
Infective exacerbation of chronic obstructive airways disease † 1	0/757 (0.00%)	1/761 (0.13%)
Neutropenic infection † 1	3/757 (0.40%)	3/761 (0.39%)
Perirectal abscess † 1	2/757 (0.26%)	0/761 (0.00%)
Injury, poisoning and procedural complications
Fracture † 1	1/757 (0.13%)	1/761 (0.13%)
Gastroenteritis radiation † 1	1/757 (0.13%)	0/761 (0.00%)
Hip fracture † 1	1/757 (0.13%)	2/761 (0.26%)
Radiation proctitis † 1	0/757 (0.00%)	4/761 (0.53%)
Venous injury † 1	0/757 (0.00%)	1/761 (0.13%)
Accidental overdose † 1	1/757 (0.13%)	1/761 (0.13%)
Contusion † 1	1/757 (0.13%)	0/761 (0.00%)
Femoral neck fracture † 1	1/757 (0.13%)	1/761 (0.13%)
Gastrointestinal anastomotic leak † 1	0/757 (0.00%)	1/761 (0.13%)
Infusion related reaction † 1	1/757 (0.13%)	0/761 (0.00%)
Joint injury † 1	1/757 (0.13%)	0/761 (0.00%)
Multiple fractures † 1	1/757 (0.13%)	0/761 (0.00%)
Tracheal obstruction † 1	1/757 (0.13%)	0/761 (0.00%)
Upper limb fracture † 1	0/757 (0.00%)	1/761 (0.13%)
Anastomotic leak † 1	0/757 (0.00%)	1/761 (0.13%)
Clavicle fracture † 1	1/757 (0.13%)	1/761 (0.13%)
Femur fracture † 1	2/757 (0.26%)	2/761 (0.26%)
Lower limb fracture † 1	0/757 (0.00%)	1/761 (0.13%)
Thoracic vertebral fracture † 1	1/757 (0.13%)	0/761 (0.00%)
Ulna fracture † 1	1/757 (0.13%)	0/761 (0.00%)
Procedural complication † 1	1/757 (0.13%)	0/761 (0.00%)
Rib fracture † 1	0/757 (0.00%)	1/761 (0.13%)
Fall † 1	3/757 (0.40%)	1/761 (0.13%)
Spinal compression fracture † 1	1/757 (0.13%)	1/761 (0.13%)
Lumbar vertebral fracture † 1	1/757 (0.13%)	0/761 (0.00%)
Overdose † 1	6/757 (0.79%)	11/761 (1.45%)
Spinal fracture † 1	3/757 (0.40%)	0/761 (0.00%)
Investigations
Aspartate aminotransferase increased † 1	1/757 (0.13%)	1/761 (0.13%)
Bone marrow myelogram abnormal † 1	0/757 (0.00%)	1/761 (0.13%)
Haemoglobin decreased † 1	3/757 (0.40%)	9/761 (1.18%)
Neutrophil count † 1	1/757 (0.13%)	0/761 (0.00%)
Neutrophil count decreased † 1	2/757 (0.26%)	0/761 (0.00%)
Transaminases increased † 1	1/757 (0.13%)	0/761 (0.00%)
Weight decreased † 1	1/757 (0.13%)	1/761 (0.13%)
Haemoglobin † 1	0/757 (0.00%)	1/761 (0.13%)
Alanine aminotransferase increased † 1	0/757 (0.00%)	1/761 (0.13%)
Clostridium test positive † 1	0/757 (0.00%)	1/761 (0.13%)
Eastern Cooperative Oncology Group performance status worsened † 1	0/757 (0.00%)	3/761 (0.39%)
Platelet count decreased † 1	1/757 (0.13%)	0/761 (0.00%)
Urine output decreased † 1	0/757 (0.00%)	1/761 (0.13%)
Blood creatinine increased † 1	1/757 (0.13%)	2/761 (0.26%)
Metabolism and nutrition disorders
Malnutrition † 1	0/757 (0.00%)	1/761 (0.13%)
Hyperkalaemia † 1	0/757 (0.00%)	1/761 (0.13%)
Hypokalaemia † 1	2/757 (0.26%)	3/761 (0.39%)
Dehydration † 1	11/757 (1.45%)	21/761 (2.76%)
Hypercalcaemia † 1	1/757 (0.13%)	1/761 (0.13%)
Hyponatraemia † 1	3/757 (0.40%)	2/761 (0.26%)
Tumour lysis syndrome † 1	1/757 (0.13%)	1/761 (0.13%)
Fluid overload † 1	0/757 (0.00%)	1/761 (0.13%)
Hypomagnesaemia † 1	1/757 (0.13%)	0/761 (0.00%)
Hypophagia † 1	1/757 (0.13%)	0/761 (0.00%)
Metabolic acidosis † 1	0/757 (0.00%)	2/761 (0.26%)
Hypoglycaemia † 1	4/757 (0.53%)	3/761 (0.39%)
Decreased appetite † 1	4/757 (0.53%)	3/761 (0.39%)
Hyperglycaemia † 1	3/757 (0.40%)	2/761 (0.26%)
Hypocalcaemia † 1	6/757 (0.79%)	4/761 (0.53%)
Hypophosphataemia † 1	1/757 (0.13%)	0/761 (0.00%)
Musculoskeletal and connective tissue disorders
Muscle spasms † 1	0/757 (0.00%)	1/761 (0.13%)
Neck pain † 1	1/757 (0.13%)	0/761 (0.00%)
Osteonecrosis † 1	1/757 (0.13%)	1/761 (0.13%)
Systemic lupus erythematosus † 1	1/757 (0.13%)	0/761 (0.00%)
Fistula † 1	0/757 (0.00%)	1/761 (0.13%)
Musculoskeletal pain † 1	3/757 (0.40%)	1/761 (0.13%)
Osteonecrosis of jaw † 1	1/757 (0.13%)	0/761 (0.00%)
Bone pain † 1	7/757 (0.92%)	4/761 (0.53%)
Flank pain † 1	0/757 (0.00%)	1/761 (0.13%)
Musculoskeletal chest pain † 1	1/757 (0.13%)	0/761 (0.00%)
Groin pain † 1	1/757 (0.13%)	0/761 (0.00%)
Hypercreatinaemia † 1	1/757 (0.13%)	0/761 (0.00%)
Pain in extremity † 1	3/757 (0.40%)	3/761 (0.39%)
Pathological fracture † 1	1/757 (0.13%)	2/761 (0.26%)
Spinal pain † 1	1/757 (0.13%)	0/761 (0.00%)
Arthralgia † 1	2/757 (0.26%)	1/761 (0.13%)
Back pain † 1	12/757 (1.59%)	7/761 (0.92%)
Muscular weakness † 1	4/757 (0.53%)	3/761 (0.39%)
Osteoarthritis † 1	0/757 (0.00%)	1/761 (0.13%)
Rotator cuff syndrome † 1	0/757 (0.00%)	1/761 (0.13%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenosquamous cell lung cancer † 1	1/757 (0.13%)	0/761 (0.00%)
Neoplasm progression † 1	0/757 (0.00%)	1/761 (0.13%)
Rectal adenocarcinoma † 1	1/757 (0.13%)	0/761 (0.00%)
Renal neoplasm † 1	0/757 (0.00%)	1/761 (0.13%)
Astrocytoma malignant † 1	1/757 (0.13%)	0/761 (0.00%)
Cancer pain † 1	0/757 (0.00%)	1/761 (0.13%)
Prostate cancer † 1	3/757 (0.40%)	2/761 (0.26%)
Colorectal cancer † 1	0/757 (0.00%)	1/761 (0.13%)
Malignant neoplasm progression † 1	1/757 (0.13%)	0/761 (0.00%)
Basal cell carcinoma † 1	0/757 (0.00%)	1/761 (0.13%)
Metastases to meninges † 1	1/757 (0.13%)	0/761 (0.00%)
Metastatic neoplasm † 1	0/757 (0.00%)	1/761 (0.13%)
Rectal cancer † 1	1/757 (0.13%)	0/761 (0.00%)
Squamous cell carcinoma of skin † 1	0/757 (0.00%)	1/761 (0.13%)
Squamous cell carcinoma of the oral cavity † 1	1/757 (0.13%)	0/761 (0.00%)
Non-small cell lung cancer † 1	0/757 (0.00%)	1/761 (0.13%)
Colorectal cancer recurrent † 1	1/757 (0.13%)	0/761 (0.00%)
Meningioma † 1	1/757 (0.13%)	0/761 (0.00%)
Metastatic squamous cell carcinoma † 1	0/757 (0.00%)	2/761 (0.26%)
Prostate cancer metastatic † 1	10/757 (1.32%)	9/761 (1.18%)
Metastasis † 1	2/757 (0.26%)	2/761 (0.26%)
Nervous system disorders
Carotid artery stenosis † 1	0/757 (0.00%)	1/761 (0.13%)
Nerve root compression † 1	0/757 (0.00%)	1/761 (0.13%)
Paraparesis † 1	1/757 (0.13%)	0/761 (0.00%)
Haemorrhage intracranial † 1	0/757 (0.00%)	1/761 (0.13%)
IIIrd nerve disorder † 1	1/757 (0.13%)	0/761 (0.00%)
Peripheral motor neuropathy † 1	4/757 (0.53%)	1/761 (0.13%)
Aphasia † 1	0/757 (0.00%)	1/761 (0.13%)
Cerebral haematoma † 1	0/757 (0.00%)	1/761 (0.13%)
Cerebral ischaemia † 1	0/757 (0.00%)	3/761 (0.39%)
Cerebrovascular accident † 1	4/757 (0.53%)	2/761 (0.26%)
Depressed level of consciousness † 1	1/757 (0.13%)	1/761 (0.13%)
Headache † 1	1/757 (0.13%)	2/761 (0.26%)
Ataxia † 1	0/757 (0.00%)	1/761 (0.13%)
Coma † 1	0/757 (0.00%)	1/761 (0.13%)
Monoplegia † 1	1/757 (0.13%)	0/761 (0.00%)
Neuralgia † 1	2/757 (0.26%)	0/761 (0.00%)
Central nervous system haemorrhage † 1	0/757 (0.00%)	1/761 (0.13%)
Cerebral haemorrhage † 1	1/757 (0.13%)	1/761 (0.13%)
Dysarthria † 1	1/757 (0.13%)	0/761 (0.00%)
Motor dysfunction † 1	1/757 (0.13%)	0/761 (0.00%)
Somnolence † 1	1/757 (0.13%)	2/761 (0.26%)
Ischaemic stroke † 1	0/757 (0.00%)	1/761 (0.13%)
Peripheral sensory neuropathy † 1	0/757 (0.00%)	1/761 (0.13%)
Syncope † 1	5/757 (0.66%)	4/761 (0.53%)
Intracranial pressure increased † 1	0/757 (0.00%)	1/761 (0.13%)
Seizure † 1	0/757 (0.00%)	2/761 (0.26%)
Transient ischaemic attack † 1	1/757 (0.13%)	1/761 (0.13%)
Dizziness † 1	2/757 (0.26%)	1/761 (0.13%)
Spinal cord compression † 1	6/757 (0.79%)	4/761 (0.53%)
Psychiatric disorders
Agitation † 1	0/757 (0.00%)	1/761 (0.13%)
Disorientation † 1	1/757 (0.13%)	0/761 (0.00%)
Mental status changes † 1	1/757 (0.13%)	0/761 (0.00%)
Depression suicidal † 1	0/757 (0.00%)	1/761 (0.13%)
Anxiety † 1	1/757 (0.13%)	0/761 (0.00%)
Confusional state † 1	2/757 (0.26%)	6/761 (0.79%)
Psychotic disorder † 1	0/757 (0.00%)	1/761 (0.13%)
Renal and urinary disorders
Acute kidney injury † 1	4/757 (0.53%)	8/761 (1.05%)
Haemoglobinuria † 1	1/757 (0.13%)	0/761 (0.00%)
Haemorrhage urinary tract † 1	0/757 (0.00%)	2/761 (0.26%)
Hydronephrosis † 1	3/757 (0.40%)	6/761 (0.79%)
Renal disorder † 1	0/757 (0.00%)	1/761 (0.13%)
Bladder neck obstruction † 1	0/757 (0.00%)	1/761 (0.13%)
Bladder obstruction † 1	3/757 (0.40%)	3/761 (0.39%)
Renal colic † 1	0/757 (0.00%)	1/761 (0.13%)
Urethral stenosis † 1	0/757 (0.00%)	1/761 (0.13%)
Renal impairment † 1	3/757 (0.40%)	0/761 (0.00%)
Urinary bladder haemorrhage † 1	1/757 (0.13%)	3/761 (0.39%)
Nephrotic syndrome † 1	0/757 (0.00%)	2/761 (0.26%)
Ureteric obstruction † 1	1/757 (0.13%)	1/761 (0.13%)
Ureteric stenosis † 1	0/757 (0.00%)	1/761 (0.13%)
Urinary bladder polyp † 1	1/757 (0.13%)	0/761 (0.00%)
Urinary retention † 1	9/757 (1.19%)	9/761 (1.18%)
Urinary tract obstruction † 1	2/757 (0.26%)	3/761 (0.39%)
Bladder outlet obstruction † 1	0/757 (0.00%)	1/761 (0.13%)
Dysuria † 1	1/757 (0.13%)	0/761 (0.00%)
Haematuria † 1	18/757 (2.38%)	10/761 (1.31%)
Renal failure † 1	5/757 (0.66%)	5/761 (0.66%)
Obstructive uropathy † 1	1/757 (0.13%)	0/761 (0.00%)
Urinary incontinence † 1	1/757 (0.13%)	0/761 (0.00%)
Urogenital haemorrhage † 1	0/757 (0.00%)	2/761 (0.26%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	1/757 (0.13%)	0/761 (0.00%)
Prostatic obstruction † 1	0/757 (0.00%)	1/761 (0.13%)
Penile pain † 1	1/757 (0.13%)	0/761 (0.00%)
Oedema genital † 1	1/757 (0.13%)	2/761 (0.26%)
Testicular mass † 1	1/757 (0.13%)	0/761 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	10/757 (1.32%)	21/761 (2.76%)
Hypoxia † 1	1/757 (0.13%)	3/761 (0.39%)
Pneumothorax † 1	0/757 (0.00%)	2/761 (0.26%)
Productive cough † 1	0/757 (0.00%)	1/761 (0.13%)
Alveolitis † 1	0/757 (0.00%)	1/761 (0.13%)
Lung disorder † 1	0/757 (0.00%)	1/761 (0.13%)
Cough † 1	1/757 (0.13%)	3/761 (0.39%)
Interstitial lung disease † 1	0/757 (0.00%)	2/761 (0.26%)
Pulmonary oedema † 1	0/757 (0.00%)	2/761 (0.26%)
Respiratory failure † 1	2/757 (0.26%)	7/761 (0.92%)
Dyspnoea exertional † 1	2/757 (0.26%)	0/761 (0.00%)
Pleural effusion † 1	1/757 (0.13%)	19/761 (2.50%)
Pneumonitis † 1	7/757 (0.92%)	7/761 (0.92%)
Acute pulmonary oedema † 1	0/757 (0.00%)	1/761 (0.13%)
Pulmonary embolism † 1	17/757 (2.25%)	5/761 (0.66%)
Pulmonary hypertension † 1	0/757 (0.00%)	2/761 (0.26%)
Pulmonary congestion † 1	0/757 (0.00%)	1/761 (0.13%)
Pulmonary venous thrombosis † 1	0/757 (0.00%)	1/761 (0.13%)
Acute respiratory distress syndrome † 1	0/757 (0.00%)	2/761 (0.26%)
Acute respiratory failure † 1	0/757 (0.00%)	1/761 (0.13%)
Chronic obstructive pulmonary disease † 1	0/757 (0.00%)	1/761 (0.13%)
Lung infiltration † 1	0/757 (0.00%)	1/761 (0.13%)
Skin and subcutaneous tissue disorders
Peau d'orange † 1	0/757 (0.00%)	1/761 (0.13%)
Rash † 1	0/757 (0.00%)	1/761 (0.13%)
Pyoderma gangrenosum † 1	1/757 (0.13%)	0/761 (0.00%)
Drug eruption † 1	1/757 (0.13%)	0/761 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	10/757 (1.32%)	1/761 (0.13%)
Hypotension † 1	8/757 (1.06%)	3/761 (0.39%)
Shock haemorrhagic † 1	1/757 (0.13%)	0/761 (0.00%)
Venous thrombosis limb † 1	1/757 (0.13%)	0/761 (0.00%)
Circulatory collapse † 1	0/757 (0.00%)	1/761 (0.13%)
Haematoma † 1	0/757 (0.00%)	1/761 (0.13%)
Aortic dissection † 1	1/757 (0.13%)	0/761 (0.00%)
Haemorrhage † 1	1/757 (0.13%)	1/761 (0.13%)
Vasculitis † 1	0/757 (0.00%)	1/761 (0.13%)
Embolism † 1	1/757 (0.13%)	0/761 (0.00%)
Infarction † 1	0/757 (0.00%)	1/761 (0.13%)
Thrombosis † 1	0/757 (0.00%)	2/761 (0.26%)
Vena cava thrombosis † 1	0/757 (0.00%)	1/761 (0.13%)
Venous thrombosis † 1	0/757 (0.00%)	1/761 (0.13%)
Hypertension † 1	1/757 (0.13%)	0/761 (0.00%)
Jugular vein thrombosis † 1	1/757 (0.13%)	0/761 (0.00%)
Peripheral vascular disorder † 1	0/757 (0.00%)	1/761 (0.13%)
Phlebitis † 1	2/757 (0.26%)	0/761 (0.00%)
Thrombophlebitis superficial † 1	1/757 (0.13%)	0/761 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Dasatinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	701/757 (92.60%)	716/761 (94.09%)
Blood and lymphatic system disorders
Anaemia † 1	142/757 (18.76%)	217/761 (28.52%)
Neutropenia † 1	67/757 (8.85%)	79/761 (10.38%)
Eye disorders
Lacrimation increased † 1	86/757 (11.36%)	48/761 (6.31%)
Gastrointestinal disorders
Dyspepsia † 1	59/757 (7.79%)	50/761 (6.57%)
Stomatitis † 1	47/757 (6.21%)	47/761 (6.18%)
Nausea † 1	231/757 (30.52%)	288/761 (37.84%)
Abdominal pain † 1	67/757 (8.85%)	66/761 (8.67%)
Diarrhoea † 1	312/757 (41.22%)	414/761 (54.40%)
Vomiting † 1	117/757 (15.46%)	166/761 (21.81%)
Constipation † 1	189/757 (24.97%)	157/761 (20.63%)
General disorders
Pain † 1	62/757 (8.19%)	47/761 (6.18%)
Pyrexia † 1	71/757 (9.38%)	132/761 (17.35%)
Mucosal inflammation † 1	52/757 (6.87%)	70/761 (9.20%)
Oedema † 1	47/757 (6.21%)	36/761 (4.73%)
Oedema peripheral † 1	207/757 (27.34%)	162/761 (21.29%)
Fatigue † 1	329/757 (43.46%)	334/761 (43.89%)
Chest pain † 1	34/757 (4.49%)	49/761 (6.44%)
Asthenia † 1	143/757 (18.89%)	163/761 (21.42%)
Infections and infestations
Urinary tract infection † 1	67/757 (8.85%)	73/761 (9.59%)
Investigations
Haemoglobin decreased † 1	27/757 (3.57%)	49/761 (6.44%)
Weight decreased † 1	77/757 (10.17%)	121/761 (15.90%)
Weight increased † 1	64/757 (8.45%)	36/761 (4.73%)
Metabolism and nutrition disorders
Dehydration † 1	23/757 (3.04%)	44/761 (5.78%)
Decreased appetite † 1	151/757 (19.95%)	207/761 (27.20%)
Hyperglycaemia † 1	55/757 (7.27%)	41/761 (5.39%)
Hypocalcaemia † 1	24/757 (3.17%)	40/761 (5.26%)
Musculoskeletal and connective tissue disorders
Muscle spasms † 1	42/757 (5.55%)	15/761 (1.97%)
Musculoskeletal pain † 1	55/757 (7.27%)	62/761 (8.15%)
Bone pain † 1	70/757 (9.25%)	61/761 (8.02%)
Musculoskeletal chest pain † 1	40/757 (5.28%)	35/761 (4.60%)
Pain in extremity † 1	128/757 (16.91%)	115/761 (15.11%)
Myalgia † 1	54/757 (7.13%)	50/761 (6.57%)
Arthralgia † 1	124/757 (16.38%)	104/761 (13.67%)
Back pain † 1	194/757 (25.63%)	148/761 (19.45%)
Muscular weakness † 1	51/757 (6.74%)	38/761 (4.99%)
Nervous system disorders
Headache † 1	65/757 (8.59%)	82/761 (10.78%)
Dysgeusia † 1	147/757 (19.42%)	165/761 (21.68%)
Neuropathy peripheral † 1	109/757 (14.40%)	83/761 (10.91%)
Peripheral sensory neuropathy † 1	106/757 (14.00%)	98/761 (12.88%)
Dizziness † 1	61/757 (8.06%)	64/761 (8.41%)
Paraesthesia † 1	59/757 (7.79%)	44/761 (5.78%)
Psychiatric disorders
Insomnia † 1	95/757 (12.55%)	76/761 (9.99%)
Renal and urinary disorders
Haematuria † 1	44/757 (5.81%)	46/761 (6.04%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	127/757 (16.78%)	154/761 (20.24%)
Cough † 1	112/757 (14.80%)	137/761 (18.00%)
Epistaxis † 1	41/757 (5.42%)	33/761 (4.34%)
Pleural effusion † 1	28/757 (3.70%)	117/761 (15.37%)
Skin and subcutaneous tissue disorders
Nail disorder † 1	119/757 (15.72%)	80/761 (10.51%)
Rash † 1	75/757 (9.91%)	106/761 (13.93%)
Alopecia † 1	326/757 (43.06%)	311/761 (40.87%)
Dry skin † 1	46/757 (6.08%)	54/761 (7.10%)
Vascular disorders
Hypertension † 1	42/757 (5.55%)	22/761 (2.89%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• EMail: Clinical.Trials@bms.com

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

de Liano AG, Reig O, Mellado B, Martin C, Rull EU, Maroto JP. Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer. Br J Cancer. 2014 Apr 29;110(9):2201-8. doi: 10.1038/bjc.2014.189. Epub 2014 Apr 10.

Araujo JC, Trudel GC, Saad F, Armstrong AJ, Yu EY, Bellmunt J, Wilding G, McCaffrey J, Serrano SV, Matveev VB, Efstathiou E, Oudard S, Morris MJ, Sizer B, Goebell PJ, Heidenreich A, de Bono JS, Begbie S, Hong JH, Richardet E, Gallardo E, Paliwal P, Durham S, Cheng S, Logothetis CJ. Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1307-16. doi: 10.1016/S1470-2045(13)70479-0. Epub 2013 Nov 8.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00744497
• Other Study ID Numbers: CA180-227; 2008-000701-11 ( EudraCT Number )
• First Submitted: August 29, 2008
• First Posted: September 1, 2008
• Results First Submitted: November 15, 2013
• Results First Posted: February 6, 2014
• Last Update Posted: October 17, 2016