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 13, 2015

Last verified: August 2015

History of Changes

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
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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
Not defined	8	10

[1]	Randomized
[2]	Remained on study drug

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
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

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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) ]

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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) ]

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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) ]

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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) ]

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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) ]

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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) ]

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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) ]

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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. ]

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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 ]

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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. ]

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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. ]

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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. ]

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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 ]

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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 ]

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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 ]

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Serious Adverse Events

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Other Adverse Events

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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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