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Study of Immunotherapy to Treat Advanced Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00861614
Recruitment Status : Completed
First Posted : March 13, 2009
Results First Posted : March 16, 2016
Last Update Posted : September 30, 2016
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: Ipilimumab
Drug: Placebo
Enrollment 988
Recruitment Details  
Pre-assignment Details 988 enrolled, 799 randomized (399 ipilimumab, 400 placebo); 149 no longer met study criteria, 17 withdrew, 6 adverse events, 4 died, 1 lost to follow-up,12 unspecified. 789 treated with radiotherapy (393 ipilimumab, 396 placebo); 2 no longer met study criteria, 3 withdrew consent, 1 died, 2 adverse events, 2 lost to follow-up.
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description Prior to receiving study drug, participants receive radiotherapy at 8 Gray units (Gy) to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up. Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Period Title: Overall Study
Started 393 396
Completed 22 28
Not Completed 371 368
Reason Not Completed
Disease Progression             182             263
Study Drug Toxicity             79             6
Death             32             19
Adverse Event             27             23
Withdrawal by Subject             34             35
Other             17             22
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy Total
Hide Arm/Group Description Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4,7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up. Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed PD, drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up. Total of all reporting groups
Overall Number of Baseline Participants 399 400 799
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 399 participants 400 participants 799 participants
68.2  (7.53) 67.1  (7.56) 67.6  (7.56)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 399 participants 400 participants 799 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
399
 100.0%
400
 100.0%
799
 100.0%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time in months from randomization date to date of death due to any cause in all randomized subjects. For participants alive at the time of the database cutoff date, OS was censored at the last date the participant was known to be alive.
Time Frame Date of randomization to date of death
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 399 400
Median (95% Confidence Interval)
Unit of Measure: months
11.04
(9.46 to 12.48)
10.02
(8.38 to 11.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab + Radiotherapy, Placebo + Radiotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0127
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.71 to 0.96
Estimation Comments Ipilimumab over placebo
2.Primary Outcome
Title Overall Survival Rate
Hide Description The overall survival (OS) rate is a percentage, representing the fraction of all randomized participants who were alive following treatment, from 1 to 5 years. OS was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.
Time Frame Date of randomization to date of death
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 399 400
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
OS Rate at Year 1
46.5
(41.6 to 51.4)
40.8
(35.9 to 45.6)
OS Rate at Year 2
25.2
(20.9 to 29.6)
16.6
(12.9 to 20.3)
OS Rate at Year 3
15.3
(11.7 to 18.9)
7.9
(5.2 to 10.6)
OS Rate at Year 4
10.1
(6.9 to 13.3)
3.3
(1.3 to 5.3)
OS Rate at Year 5
7.9
(4.4 to 11.4)
2.7
(0.8 to 4.7)
3.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description All PFS events were based on investigator’s assessment. Participants who were alive and did not experience a PFS event were censored at the earlier of the latest prostate-specific antigen (PSA) or radiological tumor assessment date. Participants who did not die, showed no clinical deterioration, and who had no recorded post-baseline PSA or radiological tumor assessment were censored at randomization date.
Time Frame Date of randomization to earliest date of confirmed PSA or radiological progression, clinical deterioration or death
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 399 400
Median (95% Confidence Interval)
Unit of Measure: months
4.01
(3.65 to 4.34)
3.06
(2.86 to 3.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab + Radiotherapy, Placebo + Radiotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.61 to 0.82
Estimation Comments Ipilimumab over placebo
4.Secondary Outcome
Title Pain Response
Hide Description The percentage of participants with a pain response assessed using the Brief Pain Inventory Short Form (BPI-SF) completed by participants throughout the study in a daily diary log. Pain-evaluable participants were defined as those with a decrease in the average daily worst pain intensity by at least 30% from baseline, maintained over 2 consecutive evaluations without the use of any rescue analgesic medication or increase in analgesic use in the same time period.
Time Frame Assessed at screening, weeks 12, 18, 24, and at the end of treatment visit
Hide Outcome Measure Data
Hide Analysis Population Description
All pain-evaluable participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 197 186
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.55
(1.44 to 7.18)
0.54
(0.01 to 2.96)
5.Secondary Outcome
Title Duration of Pain Response
Hide Description The time between the initial date of pain response and completion date of pain response. The initial date when the pain response criterion was achieved was considered the pain response date. The earlier of date of death, date of tumor resection surgery, or date when pain response criterion was no longer met was considered the completion date of the pain response. If none of these scenarios occurred, the completion of the pain response was set to the last known alive date.
Time Frame Day of initial pain response to day of completion of pain response or date of death
Hide Outcome Measure Data
Hide Analysis Population Description
All pain-evaluable participants with pain response
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 7 1
Median (95% Confidence Interval)
Unit of Measure: months
2.5
(1.5 to 3)
1.5 [1] 
(NA to NA)
[1]
CI not applicable due to only one participant
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab + Radiotherapy, Placebo + Radiotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.02 to 4.00
Estimation Comments Ipilimumab over placebo
6.Secondary Outcome
Title Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR)
Hide 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. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during study and up to 70 days after last dose. IrAEs=AEs potentially associated with inflammation and considered to be causally related to study drug and grouped into gastrointestinal (GI), hepatic, skin, endocrine and neurological. ImARs were collected prospectively and grouped into enterocolitis, hepatitis, dermatitis, neuropathies and endocrinopathies. IrAEs/ imARs were graded using Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Ver. 3.0.

Time Frame Randomization to date of death
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393 396
Measure Type: Number
Unit of Measure: participants
SAE 257 164
Treatment-Related AE 296 180
Any Death 346 371
Deaths Due to Study Drug Toxicity 7 1
Discontinuation of Study Drug due to AEs 137 62
Immune-Related AE (any grade) 250 86
Immune-Mediated Adverse Reaction (Grade >=2) 203 40
7.Secondary Outcome
Title Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE)
Hide Description The time between first dose of study drug and date of earliest Grade 3 or 4 irAE. These irAEs are AEs of unknown etiology, consistent with an immune phenomenon and considered as causally related to drug exposure. The five subcategories of irAE examined include gastrointestinal (GI), liver, skin, endocrine, and neurological and are graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.
Time Frame Day 1 to 70 days after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393 396
Median (95% Confidence Interval)
Unit of Measure: weeks
Gastrotintestinal (n= 71,3)
5.71
(5.00 to 7.00)
5.71
(0.57 to 31.86)
Liver (n= 18,5)
9.14
(8.29 to 10.43)
6.00
(3.14 to 8.57)
Skin (n=4,0)
3.71
(2.57 to 6.43)
NA [1] 
(NA to NA)
Endocrine (n=8,2)
7.93
(4.14 to 11.14)
5.00
(4.29 to 5.71)
Neurological (n= 1,0)
11.4 [2] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
There were no participants in this treatment arm who displayed irAEs of this type
[2]
CI not applicable due to only one participant
8.Secondary Outcome
Title Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE)
Hide Description Time between the date of onset of a Grade 3 or 4 irAE and the date of improvement to Grade 1 or less or the worst grade at baseline.
Time Frame Day 1 to 70 days after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393 396
Median (95% Confidence Interval)
Unit of Measure: weeks
Gastrointestinal (n=71,3)
2.9
(1.6 to 4.7)
0.9
(0.4 to 1.1)
Liver (n=18,5)
4.1
(3.6 to 8.1)
6.0 [1] 
(1.9 to NA)
Skin (n=4,0)
3.6
(2.6 to 5.9)
NA [2] 
(NA to NA)
Endocrine (n=8,2)
11.1 [1] 
(2.4 to NA)
5.9
(0.9 to 10.9)
Neurological (n=1,0)
NA [3] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
Number of subjects was too small to obtain upper limit
[2]
There were no participants in this treatment arm who displayed irAEs of this type.
[3]
No participant with resolved irAE.
9.Secondary Outcome
Title Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR)
Hide Description

The time between first dose of study drug and date of earliest Grade 3 or 4 imAR. ImARs were collected prospectively and grouped into enterocolitis, hepatitis, dermatitis, neuropathies and endocrinopathies and graded using Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Ver. 3.0.

Only the Ipilimumab + Radiotherapy group of participants was included in the analysis because ipilimumab is associated with inflammatory events resulting from increased or excessive immune activity likely to be related to its mechanism of action.

Time Frame Day 1 to time of onset of the imAR of interest
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants receiving Ipilimumab + Radiotherapy
Arm/Group Title Ipilimumab + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393
Median (Full Range)
Unit of Measure: weeks
Enterocolitis (n=65)
3.4
(0.3 to 16.6)
Hepatitis (n=17)
9.0
(1.7 to 16.9)
Dermatitis (n=3)
2.4
(0.1 to 3.1)
Endocrinopathies (n=6)
7.9
(1.7 to 10.7)
10.Secondary Outcome
Title Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0
Hide Description

Time between the date of onset of an imAR to the date of resolution date of the event or the last known date participant was alive if an event did not resolve.

Only the Ipilimumab + Radiotherapy group of participants was included in the analysis because ipilimumab is associated with inflammatory events resulting from increased or excessive immune activity likely to be related to its mechanism of action.

Time Frame Day 1 to 70 days after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants receiving Ipilimumab + Radiotherapy
Arm/Group Title Ipilimumab + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393
Median (Full Range)
Unit of Measure: weeks
Enterocolitis (n=52)
6.0
(0.1 to 40.1)
Hepatitis (n=15)
8.6
(1.1 to 19.0)
Dermatitis (n=3)
6.9
(4.0 to 12.1)
Endocrinopathies (n=0)
NA [1] 
(NA to NA)
[1]
No participant with resolved imAR
11.Secondary Outcome
Title Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline
Hide Description Comparison of baseline versus worst grade hematology laboratory tests as measured by white blood count (WBC), absolute neutrophil count (ANC), platelet count, hemoglobin and lymphocyte results. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for WBC were based on Gr 1: 3.0 - < Lower Limit of Normal (LLN); Gr 2: 2.0 - < 3.0; Gr 3: 1.0 - < 2.0; Gr4: < 1.0. Abnormal values for Hemoglobin were based on Gr 1: 10.0 - < LLN; Gr 2: 8.0 - < 10.0; Gr 3: 6.5 - < 8.0; Gr 4: < 6.5. Abnormal values for Lymphocytes were based on Gr 1: 0.8 - < 1.5; Gr 2: 0.5 - < 0.8; Gr 3): 0.2 - < 0.5; Gr 4: < 0.2. Abnormal values for ANC were based on Gr 1: 1.5 - < 2.0; Gr 2: 1.0 - < 1.5; Gr 3: 0.5 - < 1.0; Gr 4: < 0.5. Abnormal values for Platelets were based on Gr 1: 75.0 - < LLN; Gr 2: 50.0 - < 75.0; Gr 3: 25.0 - < 50.0; Gr 4: < 25.0.
Time Frame Day 1 to 70 days after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393 396
Measure Type: Number
Unit of Measure: participants
WBC Gr 0 at Baseline to Gr 3-4 3 2
WBC Gr 1 at Baseline to Gr 3-4 0 1
WBC Gr 2 at Baseline to Gr 3-4 0 1
WBC Gr 3 at Baseline to Gr 3-4 0 0
WBC Gr 4 at Baseline to Gr 3-4 0 0
WBC Not Reported at Baseline to Gr 3-4 0 0
ANC Gr 0 at Baseline to Gr 3-4 4 6
ANC Gr 1 at Baseline to Gr 3-4 0 0
ANC Gr 2 at Baseline to Gr 3-4 0 0
ANC Gr 3 at Baseline to Gr 3-4 0 0
ANC Gr 4 at Baseline to Gr 3-4 0 0
ANC Not Reported at Baseline to Gr 3-4 1 0
Platelet Count Gr 0 at Baseline to Gr 3-4 1 6
Platelet Count Gr 1 at Baseline to Gr 3-4 1 1
Platelet Count Gr 2 at Baseline to Gr 3-4 0 0
Platelet Count Gr 3 at Baseline to Gr 3-4 0 0
Platelet Count Gr 4 at Baseline to Gr 3-4 0 0
Platelet Count Not Reported at Baseline to Gr 3-4 1 1
Hemoglobin Gr 0 at Baseline to Gr 3-4 0 3
Hemoglobin Gr 1 at Baseline to Gr 3-4 16 25
Hemoglobin Gr 2 at Baseline to Gr 3-4 13 11
Hemoglobin Gr 3 at Baseline to Gr 3-4 0 1
Hemoglobin Gr 4 at Baseline to Gr 3-4 0 0
Hemoglobin Not Reported at Baseline to Gr 3-4 0 1
Lymphocytes Gr 0 at Baseline to Gr 3-4 4 1
Lymphocytes Gr 1 at Baseline to Gr 3-4 6 11
Lymphocytes Gr 2 at Baseline to Gr 3-4 11 17
Lymphocytes Gr 3 at Baseline to Gr 3-4 8 7
Lymphocytes Gr 4 at Baseline to Gr 3-4 0 0
Lymphocytes Not Reported at Baseline to Gr 3-4 3 0
12.Secondary Outcome
Title Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline
Hide Description Comparison of baseline versus worst grade liver function as measured by alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and alkaline phosphatase (ALP). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for ALP, ALT and AST were based on grades; Gr 1: > 1.0 - 2.5 * upper limits of normal (ULN); Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Abnormal values for Total Bilirubin were based on Gr 1: > 1.0 - 1.5 * upper limits of normal (ULN); Gr 2: > 1.5 - 3.0 * ULN; Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN.
Time Frame Day 1 to 70 days after last dose of study drug
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Hide Analysis Population Description
All treated participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393 396
Measure Type: Number
Unit of Measure: participants
ALT Gr 0 at Baseline to Gr 3-4 16 1
ALT Gr 1 at Baseline to Gr 3-4 1 1
ALT Gr 2 at Baseline to Gr 3-4 0 0
ALT Gr 3 at Baseline to Gr 3-4 0 0
ALT Gr 4 at Baseline to Gr 3-4 0 0
ALT Not reported at Basline to Gr 3-4 1 0
AST Gr 0 at Baseline to Gr 3-4 15 6
AST Gr 1 at Baseline to Gr 3-4 5 1
AST Gr 2 at Baseline to Gr 3-4 1 1
AST Gr 3 at Baseline to Gr 3-4 1 0
AST Gr 4 at Baseline to Gr 3-4 0 0
AST Not Reported at Baseline to Gr 3-4 1 0
Total Bilirubin Gr 0 at Baseline to Gr 3-4 6 2
Total Bilirubin Gr 1 at Baseline to Gr 3-4 1 0
Total Bilirubin Gr 2 at Baseline to Gr 3-4 1 0
Total Bilirubin Gr 3 at Baseline to Gr 3-4 0 0
Total Bilirubin Gr 4 at Baseline to Gr 3-4 0 0
Total Bilirubin Not Reported at Baseline to Gr 3-4 0 0
ALP Gr 0 at Baseline to Gr 3-4 1 1
ALP Gr 1 at Baseline to Gr 3-4 10 17
ALP Gr 2 at Baseline to Gr 3-4 21 29
ALP Gr 3 at Baseline to Gr 3-4 27 42
ALP Gr 4 at Baseline to Gr 3-4 1 0
ALP Not Reported at Baseline to Gr 3-4 0 6
13.Secondary Outcome
Title Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline
Hide Description Comparison of baseline versus worst grade serum chemistry as measured by lipase and amylase analysis. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for lipase: Gr1: > 1.0 - 1.5 * ULN; Gr2: > 1.5 - 2.0 * ULN; Gr 3: > 2.0 - 5.0 * ULN; Gr4: > 5.0*ULN. Abnormal values for amylase: Gr1: > 1.0 - 1.5 * ULN; Gr 2: > 1.5 - 2.0 * ULN; Gr 3: > 2.0 - 5.0 * ULN; Gr4: > 5.0 * ULN.
Time Frame Day 1 to 70 days after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393 396
Measure Type: Number
Unit of Measure: participants
Lipase Gr 0 at Baseline to Gr 3-4 21 10
Lipase Gr 1 at Baseline to Gr 3-4 1 1
Lipase Gr 2 at Baseline to Gr 3-4 1 0
Lipase Gr 3 at Baseline to Gr 3-4 0 1
Lipase Gr 4 at Baseline to Gr 3-4 0 0
Lipase Not reported at Basline to Gr 3-4 0 0
Amylase Gr 0 at Baseline to Gr 3-4 4 4
Amylase Gr 1 at Baseline to Gr 3-4 1 1
Amylase Gr 2 at Baseline to Gr 3-4 3 1
Amylase Gr 3 at Baseline to Gr 3-4 1 0
Amylase Gr 4 at Baseline to Gr 3-4 0 0
Amylase Not Reported at Baseline to Gr 3-4 0 0
14.Secondary Outcome
Title Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline
Hide Description Comparison of baseline versus worst grade renal function as measured by creatinine analysis. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr).Gr 0: within normal range. Abnormal values for Creatinine were based on Gr 1: > 1.0 - 1.5*ULN; Gr 2: > 1.5 - 3.0*ULN; Gr 3: > 3.0 - 6.0*ULN; Gr 4: > 6.0*ULN.
Time Frame Day 1 to 70 days after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description:
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
Overall Number of Participants Analyzed 393 396
Measure Type: Number
Unit of Measure: participants
Creatinine Gr 0 at Baseline to Gr 3-4 3 3
Creatinine Gr 1 at Baseline to Gr 3-4 0 0
Creatinine Gr 2 at Baseline to Gr 3-4 0 0
Creatinine Gr 3 at Baseline to Gr 3-4 0 0
Creatinine Gr 4 at Baseline to Gr 3-4 0 0
Creatinine Not Reported at Baseline to Gr 3-4 0 0
Time Frame Day 1 to 70 days following the last dose of study drug
Adverse Event Reporting Description Study initiated: May 2009; Study completed: August 2015
 
Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
Hide Arm/Group Description Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up. Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
All-Cause Mortality
Ipilimumab + Radiotherapy Placebo + Radiotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ipilimumab + Radiotherapy Placebo + Radiotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   257/393 (65.39%)   164/396 (41.41%) 
Blood and lymphatic system disorders     
Anaemia of malignant disease  1  0/393 (0.00%)  1/396 (0.25%) 
Leukopenia  1  1/393 (0.25%)  1/396 (0.25%) 
Thrombocytopenia  1  1/393 (0.25%)  6/396 (1.52%) 
Anaemia  1  15/393 (3.82%)  18/396 (4.55%) 
Febrile neutropenia  1  2/393 (0.51%)  1/396 (0.25%) 
Cardiac disorders     
Myocardial ischaemia  1  1/393 (0.25%)  0/396 (0.00%) 
Pericardial effusion  1  1/393 (0.25%)  0/396 (0.00%) 
Cardio-respiratory arrest  1  2/393 (0.51%)  2/396 (0.51%) 
Myocardial infarction  1  1/393 (0.25%)  1/396 (0.25%) 
Acute myocardial infarction  1  2/393 (0.51%)  1/396 (0.25%) 
Cardiac failure congestive  1  0/393 (0.00%)  1/396 (0.25%) 
Bradycardia  1  1/393 (0.25%)  0/396 (0.00%) 
Cardiac failure  1  2/393 (0.51%)  1/396 (0.25%) 
Atrial fibrillation  1  2/393 (0.51%)  2/396 (0.51%) 
Cardiac valve disease  1  0/393 (0.00%)  1/396 (0.25%) 
Cardiopulmonary failure  1  1/393 (0.25%)  1/396 (0.25%) 
Arrhythmia  1  3/393 (0.76%)  0/396 (0.00%) 
Cardiac arrest  1  2/393 (0.51%)  0/396 (0.00%) 
Cardiac failure acute  1  1/393 (0.25%)  0/396 (0.00%) 
Tachycardia  1  2/393 (0.51%)  0/396 (0.00%) 
Endocrine disorders     
Adrenocorticotropic hormone deficiency  1  1/393 (0.25%)  0/396 (0.00%) 
Hyperthyroidism  1  4/393 (1.02%)  0/396 (0.00%) 
Hypophysitis  1  2/393 (0.51%)  2/396 (0.51%) 
Hypothyroidism  1  2/393 (0.51%)  0/396 (0.00%) 
Adrenal insufficiency  1  2/393 (0.51%)  1/396 (0.25%) 
Hypopituitarism  1  3/393 (0.76%)  0/396 (0.00%) 
Eye disorders     
Pupils unequal  1  0/393 (0.00%)  1/396 (0.25%) 
Retinal vein thrombosis  1  0/393 (0.00%)  1/396 (0.25%) 
Papilloedema  1  0/393 (0.00%)  1/396 (0.25%) 
Macular degeneration  1  0/393 (0.00%)  1/396 (0.25%) 
Gastrointestinal disorders     
Colitis ulcerative  1  2/393 (0.51%)  0/396 (0.00%) 
Large intestine perforation  1  2/393 (0.51%)  0/396 (0.00%) 
Proctalgia  1  0/393 (0.00%)  1/396 (0.25%) 
Small intestinal obstruction  1  0/393 (0.00%)  1/396 (0.25%) 
Abdominal pain  1  4/393 (1.02%)  5/396 (1.26%) 
Colitis  1  21/393 (5.34%)  0/396 (0.00%) 
Femoral hernia incarcerated  1  0/393 (0.00%)  1/396 (0.25%) 
Gastric ulcer  1  1/393 (0.25%)  0/396 (0.00%) 
Gastrointestinal obstruction  1  1/393 (0.25%)  1/396 (0.25%) 
Gastrointestinal pain  1  0/393 (0.00%)  1/396 (0.25%) 
Diverticular perforation  1  1/393 (0.25%)  0/396 (0.00%) 
Proctitis  1  1/393 (0.25%)  0/396 (0.00%) 
Dysphagia  1  0/393 (0.00%)  1/396 (0.25%) 
Enterocolitis haemorrhagic  1  1/393 (0.25%)  0/396 (0.00%) 
Ileus  1  1/393 (0.25%)  0/396 (0.00%) 
Intestinal haemorrhage  1  2/393 (0.51%)  0/396 (0.00%) 
Nausea  1  11/393 (2.80%)  8/396 (2.02%) 
Oesophageal perforation  1  1/393 (0.25%)  0/396 (0.00%) 
Abdominal distension  1  1/393 (0.25%)  1/396 (0.25%) 
Diarrhoea  1  59/393 (15.01%)  6/396 (1.52%) 
Duodenitis  1  1/393 (0.25%)  0/396 (0.00%) 
Enteritis  1  1/393 (0.25%)  0/396 (0.00%) 
Gastritis  1  1/393 (0.25%)  0/396 (0.00%) 
Gastrointestinal disorder  1  1/393 (0.25%)  0/396 (0.00%) 
Haematemesis  1  0/393 (0.00%)  1/396 (0.25%) 
Rectal haemorrhage  1  1/393 (0.25%)  1/396 (0.25%) 
Constipation  1  7/393 (1.78%)  3/396 (0.76%) 
Intestinal obstruction  1  1/393 (0.25%)  0/396 (0.00%) 
Vomiting  1  11/393 (2.80%)  10/396 (2.53%) 
Abdominal pain upper  1  1/393 (0.25%)  0/396 (0.00%) 
Abdominal pain lower  1  0/393 (0.00%)  1/396 (0.25%) 
Chronic gastritis  1  1/393 (0.25%)  0/396 (0.00%) 
Gastrointestinal haemorrhage  1  2/393 (0.51%)  0/396 (0.00%) 
Melaena  1  2/393 (0.51%)  0/396 (0.00%) 
General disorders     
Device malfunction  1  1/393 (0.25%)  0/396 (0.00%) 
General physical health deterioration  1  16/393 (4.07%)  8/396 (2.02%) 
Malaise  1  7/393 (1.78%)  1/396 (0.25%) 
Mucosal inflammation  1  1/393 (0.25%)  0/396 (0.00%) 
Fatigue  1  13/393 (3.31%)  10/396 (2.53%) 
Oedema peripheral  1  1/393 (0.25%)  0/396 (0.00%) 
Pyrexia  1  17/393 (4.33%)  2/396 (0.51%) 
Peripheral swelling  1  0/393 (0.00%)  1/396 (0.25%) 
Chest pain  1  2/393 (0.51%)  3/396 (0.76%) 
Chills  1  2/393 (0.51%)  0/396 (0.00%) 
Asthenia  1  9/393 (2.29%)  4/396 (1.01%) 
Pain  1  6/393 (1.53%)  10/396 (2.53%) 
Performance status decreased  1  1/393 (0.25%)  0/396 (0.00%) 
Death  1  2/393 (0.51%)  1/396 (0.25%) 
Multi-organ failure  1  2/393 (0.51%)  4/396 (1.01%) 
Hepatobiliary disorders     
Hepatitis  1  4/393 (1.02%)  0/396 (0.00%) 
Cholecystitis acute  1  1/393 (0.25%)  0/396 (0.00%) 
Hepatic failure  1  1/393 (0.25%)  0/396 (0.00%) 
Cholecystitis  1  2/393 (0.51%)  0/396 (0.00%) 
Hepatotoxicity  1  1/393 (0.25%)  0/396 (0.00%) 
Autoimmune hepatitis  1  1/393 (0.25%)  0/396 (0.00%) 
Cholangitis  1  1/393 (0.25%)  0/396 (0.00%) 
Cholecystitis chronic  1  1/393 (0.25%)  0/396 (0.00%) 
Jaundice cholestatic  1  0/393 (0.00%)  1/396 (0.25%) 
Immune system disorders     
Hypersensitivity  1  2/393 (0.51%)  0/396 (0.00%) 
Autoimmune disorder  1  1/393 (0.25%)  0/396 (0.00%) 
Infections and infestations     
Cellulitis  1  1/393 (0.25%)  2/396 (0.51%) 
Epstein-Barr virus infection  1  1/393 (0.25%)  0/396 (0.00%) 
Central nervous system infection  1  0/393 (0.00%)  1/396 (0.25%) 
Pneumonia  1  18/393 (4.58%)  5/396 (1.26%) 
Anal abscess  1  0/393 (0.00%)  1/396 (0.25%) 
Cavernous sinus thrombosis  1  0/393 (0.00%)  1/396 (0.25%) 
Febrile infection  1  1/393 (0.25%)  0/396 (0.00%) 
Labyrinthitis  1  1/393 (0.25%)  0/396 (0.00%) 
Lower respiratory tract infection  1  1/393 (0.25%)  0/396 (0.00%) 
Streptococcal bacteraemia  1  1/393 (0.25%)  0/396 (0.00%) 
Viral infection  1  0/393 (0.00%)  1/396 (0.25%) 
Anal infection  1  1/393 (0.25%)  0/396 (0.00%) 
Bacterial sepsis  1  0/393 (0.00%)  1/396 (0.25%) 
Gastroenteritis  1  2/393 (0.51%)  0/396 (0.00%) 
Herpes zoster  1  1/393 (0.25%)  1/396 (0.25%) 
Lobar pneumonia  1  1/393 (0.25%)  1/396 (0.25%) 
Periorbital cellulitis  1  1/393 (0.25%)  0/396 (0.00%) 
Septic shock  1  1/393 (0.25%)  0/396 (0.00%) 
Spinal cord infection  1  0/393 (0.00%)  1/396 (0.25%) 
Bronchopneumonia  1  0/393 (0.00%)  3/396 (0.76%) 
Gastroenteritis viral  1  1/393 (0.25%)  0/396 (0.00%) 
Lung infection  1  1/393 (0.25%)  0/396 (0.00%) 
Subcutaneous abscess  1  2/393 (0.51%)  0/396 (0.00%) 
Urinary tract infection  1  12/393 (3.05%)  4/396 (1.01%) 
Cystitis  1  1/393 (0.25%)  0/396 (0.00%) 
Escherichia urinary tract infection  1  0/393 (0.00%)  1/396 (0.25%) 
Respiratory tract infection  1  2/393 (0.51%)  1/396 (0.25%) 
Urosepsis  1  0/393 (0.00%)  1/396 (0.25%) 
Bronchitis bacterial  1  0/393 (0.00%)  1/396 (0.25%) 
Infection  1  2/393 (0.51%)  2/396 (0.51%) 
Pyelonephritis  1  1/393 (0.25%)  0/396 (0.00%) 
Sepsis  1  6/393 (1.53%)  3/396 (0.76%) 
Injury, poisoning and procedural complications     
Fall  1  1/393 (0.25%)  0/396 (0.00%) 
Humerus fracture  1  1/393 (0.25%)  0/396 (0.00%) 
Fracture  1  2/393 (0.51%)  0/396 (0.00%) 
Toxicity to various agents  1  1/393 (0.25%)  0/396 (0.00%) 
Hip fracture  1  1/393 (0.25%)  0/396 (0.00%) 
Femoral neck fracture  1  0/393 (0.00%)  1/396 (0.25%) 
Ankle fracture  1  1/393 (0.25%)  0/396 (0.00%) 
Bone fissure  1  1/393 (0.25%)  0/396 (0.00%) 
Subdural haematoma  1  2/393 (0.51%)  2/396 (0.51%) 
Femur fracture  1  1/393 (0.25%)  0/396 (0.00%) 
Investigations     
Blood bilirubin increased  1  1/393 (0.25%)  0/396 (0.00%) 
Blood creatine phosphokinase increased  1  1/393 (0.25%)  0/396 (0.00%) 
Blood creatinine increased  1  3/393 (0.76%)  1/396 (0.25%) 
C-reactive protein increased  1  1/393 (0.25%)  0/396 (0.00%) 
Liver function test abnormal  1  3/393 (0.76%)  0/396 (0.00%) 
Red blood cell count decreased  1  0/393 (0.00%)  1/396 (0.25%) 
Aspartate aminotransferase increased  1  7/393 (1.78%)  0/396 (0.00%) 
Eastern Cooperative Oncology Group performance status worsened  1  0/393 (0.00%)  2/396 (0.51%) 
Haemoglobin decreased  1  13/393 (3.31%)  7/396 (1.77%) 
Blood creatine phosphokinase decreased  1  1/393 (0.25%)  0/396 (0.00%) 
Platelet count decreased  1  0/393 (0.00%)  2/396 (0.51%) 
Alanine aminotransferase increased  1  6/393 (1.53%)  0/396 (0.00%) 
General physical condition abnormal  1  0/393 (0.00%)  2/396 (0.51%) 
Weight decreased  1  2/393 (0.51%)  0/396 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  18/393 (4.58%)  10/396 (2.53%) 
Decreased appetite  1  3/393 (0.76%)  2/396 (0.51%) 
Hypokalaemia  1  2/393 (0.51%)  0/396 (0.00%) 
Hyponatraemia  1  3/393 (0.76%)  0/396 (0.00%) 
Failure to thrive  1  1/393 (0.25%)  0/396 (0.00%) 
Hypocalcaemia  1  3/393 (0.76%)  1/396 (0.25%) 
Hyperglycaemia  1  0/393 (0.00%)  1/396 (0.25%) 
Hypoglycaemia  1  0/393 (0.00%)  1/396 (0.25%) 
Tumour lysis syndrome  1  1/393 (0.25%)  0/396 (0.00%) 
Musculoskeletal and connective tissue disorders     
Flank pain  1  0/393 (0.00%)  1/396 (0.25%) 
Musculoskeletal pain  1  0/393 (0.00%)  5/396 (1.26%) 
Spinal pain  1  0/393 (0.00%)  1/396 (0.25%) 
Pathological fracture  1  1/393 (0.25%)  0/396 (0.00%) 
Groin pain  1  0/393 (0.00%)  1/396 (0.25%) 
Musculoskeletal chest pain  1  1/393 (0.25%)  0/396 (0.00%) 
Neck pain  1  1/393 (0.25%)  1/396 (0.25%) 
Pain in extremity  1  3/393 (0.76%)  2/396 (0.51%) 
Muscular weakness  1  5/393 (1.27%)  0/396 (0.00%) 
Arthralgia  1  2/393 (0.51%)  2/396 (0.51%) 
Back pain  1  7/393 (1.78%)  8/396 (2.02%) 
Bone pain  1  4/393 (1.02%)  4/396 (1.01%) 
Myalgia  1  0/393 (0.00%)  1/396 (0.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  0/393 (0.00%)  1/396 (0.25%) 
Plasma cell myeloma  1  0/393 (0.00%)  1/396 (0.25%) 
Cerebellopontine angle tumour  1  1/393 (0.25%)  0/396 (0.00%) 
Metastases to central nervous system  1  0/393 (0.00%)  2/396 (0.51%) 
Prostate cancer  1  1/393 (0.25%)  0/396 (0.00%) 
Lymphangiosis carcinomatosa  1  1/393 (0.25%)  0/396 (0.00%) 
Malignant neoplasm of spinal cord  1  1/393 (0.25%)  0/396 (0.00%) 
Metastases to bone  1  1/393 (0.25%)  1/396 (0.25%) 
Malignant neoplasm progression  1  36/393 (9.16%)  31/396 (7.83%) 
Tumour pain  1  1/393 (0.25%)  1/396 (0.25%) 
Prostate cancer metastatic  1  1/393 (0.25%)  0/396 (0.00%) 
Nervous system disorders     
Headache  1  1/393 (0.25%)  3/396 (0.76%) 
Paraparesis  1  1/393 (0.25%)  1/396 (0.25%) 
Lethargy  1  2/393 (0.51%)  1/396 (0.25%) 
Trigeminal nerve disorder  1  0/393 (0.00%)  1/396 (0.25%) 
Central nervous system haemorrhage  1  0/393 (0.00%)  2/396 (0.51%) 
Cerebrovascular accident  1  3/393 (0.76%)  2/396 (0.51%) 
Dizziness  1  1/393 (0.25%)  1/396 (0.25%) 
Neurological symptom  1  0/393 (0.00%)  1/396 (0.25%) 
Paresis  1  0/393 (0.00%)  1/396 (0.25%) 
Cerebral haematoma  1  1/393 (0.25%)  0/396 (0.00%) 
Cerebral haemorrhage  1  2/393 (0.51%)  0/396 (0.00%) 
Cerebral infarction  1  0/393 (0.00%)  1/396 (0.25%) 
Cerebral ischaemia  1  1/393 (0.25%)  0/396 (0.00%) 
Hypoaesthesia  1  0/393 (0.00%)  1/396 (0.25%) 
Peripheral motor neuropathy  1  4/393 (1.02%)  1/396 (0.25%) 
Haemorrhage intracranial  1  0/393 (0.00%)  1/396 (0.25%) 
Spinal cord compression  1  4/393 (1.02%)  2/396 (0.51%) 
Epilepsy  1  0/393 (0.00%)  1/396 (0.25%) 
Tongue paralysis  1  0/393 (0.00%)  1/396 (0.25%) 
Cerebrovascular disorder  1  0/393 (0.00%)  1/396 (0.25%) 
Depressed level of consciousness  1  1/393 (0.25%)  0/396 (0.00%) 
Peripheral sensory neuropathy  1  0/393 (0.00%)  2/396 (0.51%) 
Syncope  1  1/393 (0.25%)  2/396 (0.51%) 
Brachial plexopathy  1  0/393 (0.00%)  1/396 (0.25%) 
Paraesthesia  1  0/393 (0.00%)  1/396 (0.25%) 
Paraplegia  1  0/393 (0.00%)  1/396 (0.25%) 
Seizure  1  1/393 (0.25%)  0/396 (0.00%) 
Somnolence  1  1/393 (0.25%)  1/396 (0.25%) 
Subarachnoid haemorrhage  1  0/393 (0.00%)  1/396 (0.25%) 
Psychiatric disorders     
Depression  1  1/393 (0.25%)  0/396 (0.00%) 
Hallucination  1  1/393 (0.25%)  0/396 (0.00%) 
Self injurious behaviour  1  1/393 (0.25%)  0/396 (0.00%) 
Anxiety  1  0/393 (0.00%)  1/396 (0.25%) 
Confusional state  1  3/393 (0.76%)  3/396 (0.76%) 
Renal and urinary disorders     
Acute prerenal failure  1  0/393 (0.00%)  1/396 (0.25%) 
Urinary tract obstruction  1  1/393 (0.25%)  0/396 (0.00%) 
Hydronephrosis  1  2/393 (0.51%)  3/396 (0.76%) 
Renal impairment  1  1/393 (0.25%)  2/396 (0.51%) 
Bladder dilatation  1  1/393 (0.25%)  0/396 (0.00%) 
Bladder obstruction  1  1/393 (0.25%)  0/396 (0.00%) 
Nephrolithiasis  1  1/393 (0.25%)  0/396 (0.00%) 
Renal injury  1  1/393 (0.25%)  0/396 (0.00%) 
Ureteric obstruction  1  2/393 (0.51%)  0/396 (0.00%) 
Anuria  1  0/393 (0.00%)  1/396 (0.25%) 
Renal failure  1  4/393 (1.02%)  1/396 (0.25%) 
Acute kidney injury  1  7/393 (1.78%)  2/396 (0.51%) 
Haematuria  1  6/393 (1.53%)  6/396 (1.52%) 
Urinary retention  1  2/393 (0.51%)  2/396 (0.51%) 
Urethral obstruction  1  0/393 (0.00%)  1/396 (0.25%) 
Respiratory, thoracic and mediastinal disorders     
Lung infiltration  1  1/393 (0.25%)  0/396 (0.00%) 
Acute respiratory failure  1  0/393 (0.00%)  1/396 (0.25%) 
Dyspnoea  1  8/393 (2.04%)  6/396 (1.52%) 
Pneumonitis  1  1/393 (0.25%)  0/396 (0.00%) 
Aspiration  1  1/393 (0.25%)  0/396 (0.00%) 
Epistaxis  1  0/393 (0.00%)  1/396 (0.25%) 
Acute pulmonary oedema  1  2/393 (0.51%)  0/396 (0.00%) 
Lung disorder  1  0/393 (0.00%)  1/396 (0.25%) 
Pleural effusion  1  4/393 (1.02%)  6/396 (1.52%) 
Pulmonary embolism  1  3/393 (0.76%)  4/396 (1.01%) 
Pulmonary hypertension  1  0/393 (0.00%)  1/396 (0.25%) 
Pulmonary oedema  1  1/393 (0.25%)  0/396 (0.00%) 
Bronchospasm  1  1/393 (0.25%)  1/396 (0.25%) 
Hypoxia  1  0/393 (0.00%)  1/396 (0.25%) 
Respiratory failure  1  0/393 (0.00%)  1/396 (0.25%) 
Pneumonia aspiration  1  2/393 (0.51%)  0/396 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  3/393 (0.76%)  1/396 (0.25%) 
Hyperhidrosis  1  0/393 (0.00%)  1/396 (0.25%) 
Vascular disorders     
Hypovolaemic shock  1  1/393 (0.25%)  1/396 (0.25%) 
Venous thrombosis  1  1/393 (0.25%)  0/396 (0.00%) 
Deep vein thrombosis  1  1/393 (0.25%)  2/396 (0.51%) 
Hypertensive crisis  1  1/393 (0.25%)  0/396 (0.00%) 
Peripheral ischaemia  1  0/393 (0.00%)  1/396 (0.25%) 
Thrombosis  1  1/393 (0.25%)  0/396 (0.00%) 
Hypotension  1  3/393 (0.76%)  1/396 (0.25%) 
Vasculitis  1  1/393 (0.25%)  0/396 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ipilimumab + Radiotherapy Placebo + Radiotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   350/393 (89.06%)   333/396 (84.09%) 
Blood and lymphatic system disorders     
Anaemia  1  79/393 (20.10%)  81/396 (20.45%) 
Gastrointestinal disorders     
Abdominal pain  1  33/393 (8.40%)  25/396 (6.31%) 
Nausea  1  126/393 (32.06%)  104/396 (26.26%) 
Diarrhoea  1  186/393 (47.33%)  94/396 (23.74%) 
Constipation  1  66/393 (16.79%)  82/396 (20.71%) 
Vomiting  1  107/393 (27.23%)  80/396 (20.20%) 
General disorders     
Fatigue  1  144/393 (36.64%)  120/396 (30.30%) 
Oedema peripheral  1  46/393 (11.70%)  33/396 (8.33%) 
Pyrexia  1  81/393 (20.61%)  50/396 (12.63%) 
Asthenia  1  80/393 (20.36%)  64/396 (16.16%) 
Pain  1  33/393 (8.40%)  44/396 (11.11%) 
Infections and infestations     
Urinary tract infection  1  24/393 (6.11%)  24/396 (6.06%) 
Investigations     
Aspartate aminotransferase increased  1  31/393 (7.89%)  21/396 (5.30%) 
Haemoglobin decreased  1  26/393 (6.62%)  20/396 (5.05%) 
Alanine aminotransferase increased  1  26/393 (6.62%)  9/396 (2.27%) 
Weight decreased  1  91/393 (23.16%)  56/396 (14.14%) 
Metabolism and nutrition disorders     
Dehydration  1  26/393 (6.62%)  15/396 (3.79%) 
Decreased appetite  1  119/393 (30.28%)  97/396 (24.49%) 
Hypokalaemia  1  20/393 (5.09%)  10/396 (2.53%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal pain  1  32/393 (8.14%)  44/396 (11.11%) 
Pain in extremity  1  31/393 (7.89%)  41/396 (10.35%) 
Arthralgia  1  44/393 (11.20%)  57/396 (14.39%) 
Back pain  1  56/393 (14.25%)  74/396 (18.69%) 
Bone pain  1  31/393 (7.89%)  53/396 (13.38%) 
Nervous system disorders     
Headache  1  38/393 (9.67%)  31/396 (7.83%) 
Dizziness  1  22/393 (5.60%)  18/396 (4.55%) 
Psychiatric disorders     
Depression  1  10/393 (2.54%)  20/396 (5.05%) 
Insomnia  1  31/393 (7.89%)  34/396 (8.59%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  36/393 (9.16%)  27/396 (6.82%) 
Dyspnoea  1  47/393 (11.96%)  32/396 (8.08%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  99/393 (25.19%)  22/396 (5.56%) 
Rash  1  81/393 (20.61%)  27/396 (6.82%) 
Vascular disorders     
Hypertension  1  20/393 (5.09%)  13/396 (3.28%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
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.
Results Point of Contact
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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):
Trump D. Commentary on: "Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): A multicentre, randomised, double-blind, phase 3 trial." Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengeløv L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR, CA184-043 Investigators. Departments of Urology and Immunology and Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA, Electronic address: kwon.eugene@mayo.edu; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Brady Urological Institute, Baltimore, MD, USA; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA; Institut Gustave Roussy, University of Paris-Sud, Villejuif, France; Institut Gustave Roussy, Villejuif, France; VU University Medical Centre, Amsterdam, Netherlands; Vienna General Hospital, Medical University Vienna, Vienna, Austria; Institut Bergonié, Bordeaux, France; CHU Caremeau, Nimes, France; Centro Médico Austral, Buenos Aires, Argentina; Centre Jean Perrin, Clermont-Ferrand, France; St John of God Hospital, Subiaco, WA, Australia; University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy; Hospital de Caridade de Ijuí, Ijuí, Brazil; Nottingham University Hospital, Nottingham, UK; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; Netherlands Cancer Institute and Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; Institute of Oncology Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania; Hospital Británico de Buenos Aires, Buenos Aires, Argentina; Herlev Hospital, Herlev, Denmark; Odense University Hospital, Odense, Denmark; University of Texas MD Anderson Cancer Center, Houston,. Urol Oncol. 2016 May;34(5):249-50. doi: 10.1016/j.urolonc.2015.03.013. Epub 2015 Apr 20.
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00861614     History of Changes
Other Study ID Numbers: CA184-043
2008-003314-97
First Submitted: March 12, 2009
First Posted: March 13, 2009
Results First Submitted: March 15, 2016
Results First Posted: March 16, 2016
Last Update Posted: September 30, 2016