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Study of Immunotherapy to Treat Advanced Prostate Cancer

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00861614
Collaborator
(none)
988
Enrollment
159
Locations
2
Arms
75
Duration (Months)
6.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to determine if advanced prostate cancer patients that are treated with radiotherapy (RT) plus ipilimumab live longer that those treated with RT alone

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
988 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Phase 3 Trial Comparing Ipilimumab vs. Placebo Following Radiotherapy in Subjects With Castration Resistant Prostate Cancer That Have Received Prior Treatment With Docetaxel
Study Start Date :
May 1, 2009
Actual Primary Completion Date :
Nov 1, 2012
Actual Study Completion Date :
Aug 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Ipilimumab

Drug: Ipilimumab
5 mg/ml solution, Intravenous, 10 mg/kg, Every 3 weeks for up to 4 doses in the Induction Phase. Every 12 weeks in the Maintenance Phase, Up to 24 weeks in Induction, 48+ weeks in the Maintenance Phase, or until Treatment Stopping Criteria are met, withdrawal of consent, lost to follow-up, death, study closure
Other Names:
  • BMS 734016

    		•
    Placebo Comparator: Placebo

    Drug: Placebo
    Solution, Intravenous, 0 mg, Every 3 weeks for up to 4 doses in the Induction Phase. Every 12 weeks in the Maintenance Phase, up to 24 weeks in Induction, 48+ weeks in the Maintenance Phase, or until Treatment Stopping Criteria are met, withdrawal of consent, lost to follow-up, death, study closure

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Date of randomization to date of death]

      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.

    2. Overall Survival Rate [Date of randomization to date of death]

      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.

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) [Date of randomization to earliest date of confirmed PSA or radiological progression, clinical deterioration or death]

      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.

    2. Pain Response [Assessed at screening, weeks 12, 18, 24, and at the end of treatment visit]

      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.

    3. Duration of Pain Response [Day of initial pain response to day of completion of pain response or date of death]

      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.

    4. 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) [Randomization to date of death]

      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.

    5. Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE) [Day 1 to 70 days after last dose of study drug]

      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.

    6. Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE) [Day 1 to 70 days after last dose of study drug]

      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.

    7. Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR) [Day 1 to time of onset of the imAR of interest]

      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.

    8. Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0 [Day 1 to 70 days after last dose of study drug]

      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.

    9. Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline [Day 1 to 70 days after last dose of study drug]

      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.

    10. Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline [Day 1 to 70 days after last dose of study drug]

      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.

    11. Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline [Day 1 to 70 days after last dose of study drug]

      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.

    12. Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline [Day 1 to 70 days after last dose of study drug]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No

    For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

    Inclusion Criteria:

    • Advanced prostate cancer

    • At least 1 bone metastasis

    • Testosterone < 50 ng/dl

    • Prior treatment with docetaxel

    Exclusion Criteria:

    • Brain metastasis

    • Autoimmune disease

    • Known HIV, Hep B, or Hep C infection

    • More than 2 prior systemic anticancer regimens for prostate cancer

    • Prior treatment on BMS CA180227 for prostate cancer

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Southern Cancer Center Mobile Alabama United States 36608
    2 Alaska Clinical Research Center, Llc Anchorage Alaska United States 99508
    3 Arizona Clinical Research Center, Inc. Tucson Arizona United States 85715
    4 Highlands Oncology Group, P.A. Fayetteville Arkansas United States 72703
    5 Marsha G. Fink, Md, Inc. Fountain Valley California United States 92708
    6 Loma Linda University Cancer Center Loma Linda California United States 92350
    7 Usc/Norris Comprehensive Cancer Center Los Angeles California United States 90033
    8 Prostate Oncology Specialists, Inc. Marina Del Rey California United States 90292
    9 Comprehensive Cancer Center Palm Springs California United States 92262
    10 Va San Diego Healthcare System San Diego California United States 92161
    11 Pacific Hematology Oncology Associates San Francisco California United States 94115
    12 Baptist Cancer Institute Jacksonville Florida United States 32207
    13 Orlando Health, Inc Orlando Florida United States 32806
    14 Suburban Hematology-Oncology Associates, Pc Lawrenceville Georgia United States 30046
    15 University Of Chicago Chicago Illinois United States 60637
    16 Cancer Care Specialists Of Central Illinois Decatur Illinois United States 62526
    17 Edward Cancer Center Naperville Illinois United States 60540
    18 Mid-Illinois Hematology & Oncology Associates, Ltd Normal Illinois United States 61761
    19 University Of Iowa Hospitals And Clinics Iowa City Iowa United States 52242
    20 Siouxland Hematology-Oncology Assoc., Llp Sioux City Iowa United States 51101
    21 Hutchinson Clinic, Pa Hutchinson Kansas United States 67502
    22 Kentucky Cancer Clinic Hazard Kentucky United States 41701
    23 The Bunting-Blaustein Cancer Research Building Baltimore Maryland United States 21231
    24 Frederick Memorial Hospital Regional Cancer Therapy Center Frederick Maryland United States 21701
    25 Dana Farber Cancer Institute Boston Massachusetts United States 02115
    26 Mayo Clinic Rochester Minnesota United States 55905
    27 Kansas City Veterans Affairs Medical Center Kansas City Missouri United States 64128
    28 St Johns Medical Research Institute, Inc. Springfield Missouri United States 65807
    29 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    30 Weill Cornell Medical College New York New York United States 10065
    31 Raleigh Hematology Oncology Associates Raleigh North Carolina United States 27607
    32 Gabrail Cancer Center Canton Ohio United States 44718
    33 University Of Cincinnati Cincinnati Ohio United States 45267
    34 Providence Portland Medical Center Portland Oregon United States 97213
    35 St. Luke'S Hospital & Health Network Laboratory Bethlehem Pennsylvania United States 18015
    36 Va Pittsburgh Healthcare System Pittsburgh Pennsylvania United States 15240
    37 Associates In Hematology & Oncology, P.C. Upland Pennsylvania United States 19013
    38 Musc Hollings Cancer Center Charleston South Carolina United States 29445
    39 Center For Oncology Research & Treatment, P.A. Dallas Texas United States 75230
    40 The Center For Cancer And Blood Disorders Fort Worth Texas United States 76104
    41 The University Of Texas Md Anderson Cancer Center Houston Texas United States 77030
    42 Northwest Cancer Center Houston Texas United States 77090
    43 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    44 Edwards Comprehensive Cancer Center Huntington West Virginia United States 25701
    45 Local Institution Caba Buenos Aires Argentina 1417
    46 Local Institution Capital Federal Buenos Aires Argentina 1426
    47 Local Institution Rosario Santa Fe Argentina 2000
    48 Local Institution Rosario Santa Fe Argentina S2000DSK
    49 Local Institution San Miguel De Tucuman Tucuman Argentina 4000
    50 Local Institution San Miguel De Tucuman Tucuman Argentina T4000IAK
    51 Local Institution Buenos Aires Argentina 1019
    52 Local Institution Buenos Aires Argentina 1120
    53 Local Institution Buenos Aires Argentina C1280AEB
    54 Local Institution Buenos Aires Argentina C1426ANZ
    55 Local Institution Cordoba Argentina X5002AOQ
    56 Local Institution Cordoba Argentina X5006HBF
    57 Local Institution La Rioja Argentina 5300
    58 Local Institution Box Hill Victoria Australia 3128
    59 Local Institution Frankston Victoria Australia 3199
    60 Local Institution Heidelberg Victoria Australia 3084
    61 Local Institution Subiaco Western Australia Australia 6008
    62 Local Institution Salzburg Austria 5020
    63 Local Institution Wien Austria 1090
    64 Local Institution Brussels Belgium 1090
    65 Local Institution Bruxelles Belgium 1000
    66 Local Institution Bruxelles Belgium 1200
    67 Local Institution Roeselare Belgium 8800
    68 Local Institution Fortaleza Ceara Brazil 60430
    69 Local Institution Curitiba Parana Brazil 80440
    70 Local Institution Ijui Rio Grande Do Sul Brazil 98700000
    71 Local Institution Porto Alegre Rio Grande Do Sul Brazil 90430
    72 Local Institution Porto Alegre Rio Grande Do Sul Brazil 90610
    73 Local Institution Curitiba Sao Paulo Brazil 80530
    74 Local Institution Divinopolis Sao Paulo Brazil 35500
    75 Local Institution Mogi Das Cruzes Sao Paulo Brazil 08730
    76 Local Institution Sao Paulo Brazil 05403
    77 Local Institution Sao Paulo Brazil 09060
    78 Local Institution Greenfield Park Quebec Canada J4V 2H1
    79 Local Institution Montreal Quebec Canada H2L 4M1
    80 Local Institution Temuco Araucania Chile
    81 Local Institution Santiago - Independencia Metropolitana Chile
    82 Local Institution Santiago De Chile Metropolitana Chile 7650635
    83 Local Institution Santiago Metropolitana Chile 7510032
    84 Local Institution Vi?a Del Mar Valparaiso Chile
    85 Local Institution Monteria Cordoba Colombia
    86 Local Institution Bogota Colombia
    87 Local Institution Brno Czech Republic 656 91
    88 Local Institution Hradec Kralove Czech Republic 500 05
    89 Local Institution Liberec Czech Republic 460 63
    90 Local Institution Aalborg Denmark 9000
    91 Local Institution Aarhus Denmark 8000
    92 Local Institution Herlev Denmark 2730
    93 Local Institution Kobenhavn O Denmark 2100
    94 Local Institution Odense C Denmark 5000
    95 Local Institution Besancon Cedex France 25030
    96 Local Institution Bordeaux France 33076
    97 Local Institution Clermont-ferrand France 63000
    98 Local Institution Marseille Cedex 20 France 13915
    99 Local Institution Pointe A Pitre France 97159
    100 Local Institution Villejuif Cedex France 94800
    101 Local Institution Berlin Germany 14197
    102 Local Institution Bonn Germany 53127
    103 Local Institution Eschweiler Germany 52249
    104 Local Institution Mannheim Germany 68167
    105 Local Institution Wuppertal Germany 42103
    106 Local Institution Athens Greece 115 28
    107 Local Institution Budapest Hungary 1122
    108 Local Institution Gyula Hungary 5700
    109 Local Institution Kaposvar Hungary 7400
    110 Local Institution Kecskemet Hungary 6000
    111 Local Institution Dublin 7 Dublin Ireland
    112 Local Institution Tallaght Dublin Ireland DUBLIN 24
    113 Local Institution Dublin Ireland
    114 Local Institution Beer Jacob Israel 70300
    115 Local Institution Beer-sheva Israel 84101
    116 Local Institution Haifa Israel 31096
    117 Local Institution Tel Aviv Israel 64239
    118 Local Institution Tel Hashomer Israel 52621
    119 Local Institution Meldola (fc) Italy 47014
    120 Local Institution Milano Italy 20132
    121 Local Institution Napoli Italy 80131
    122 Local Institution Rimini Italy 47900
    123 Local Institution Siena Italy 53100
    124 Local Institution Sondrio Italy 23100
    125 Local Institution Df Distrito Federal Mexico 06720
    126 Local Institution Mexico Distrito Federal Mexico 07760
    127 Local Institution Acapulco Guerrero Mexico 39570
    128 Local Institution Guadalajara Jalisco Mexico
    129 Local Institution Cuernavaca Morelos Mexico 62290
    130 Local Institution Aguascalientes Mexico 20234
    131 Local Institution Puebla Mexico 72270
    132 Local Institution Amsterdam Netherlands 1066 CX
    133 Local Institution Mb Amsterdam Netherlands 1007MB
    134 Local Institution Arequipa Peru AREQUIPA54
    135 Local Institution Lima Peru 18
    136 Local Institution Lima Peru 34
    137 Local Institution Lima Peru L-27
    138 Local Institution Lima Peru LIMA 11
    139 Local Institution Olsztyn Poland 10-228
    140 Ponce School Of Medicine Ponce Puerto Rico 00716
    141 Local Institution Bucharest Romania 011172
    142 Local Institution Romania Romania 400015
    143 Local Institution Suceava Romania 720237
    144 Local Institution Moscow Russian Federation 115478
    145 Local Institution Moscow Russian Federation 117997
    146 Local Institution Moscow Russian Federation 129128
    147 Local Institution Obninsk Russian Federation 249036
    148 Local Institution St Petersburg Russian Federation 197758
    149 Local Institution Barcelona Spain 08035
    150 Local Institution Barcelona Spain 08208
    151 Local Institution Benidorm-alicante Spain 03501
    152 Local Institution Madrid Spain 28922
    153 Local Institution Santiago De Compostela Spain 157706
    154 Local Institution Valencia Spain 46009
    155 Local Institution Chelmsford Essex United Kingdom CM1 7ET
    156 Local Institution Cardiff Glamorgan United Kingdom CF14 2TL
    157 Local Institution Manchester Greater Manchester United Kingdom M20 4BX
    158 Local Institution Scunthorpe Lincolnshire United Kingdom DN15 7BH
    159 Local Institution Nottingham Nottinghamshire United Kingdom NG5 1PB

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00861614
    Other Study ID Numbers:
    • CA184-043
    • 2008-003314-97
    First Posted:
    Mar 13, 2009
    Last Update Posted:
    Sep 30, 2016
    Last Verified:
    Aug 1, 2016
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Ipilimumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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
    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

    Baseline Characteristics

    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy Total
    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 Participants 399 400 799
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    68.2
    (7.53)
    67.1
    (7.56)
    67.6
    (7.56)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    399
    100%
    400
    100%
    799
    100%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival (OS)
    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

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 399 400
    Median (95% Confidence Interval) [months]
    11.04
    10.02
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab + Radiotherapy, Placebo + Radiotherapy
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0127
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.83
    Confidence Interval (2-Sided) 95%
    0.71 to 0.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ipilimumab over placebo
    2. Primary Outcome
    Title Overall Survival Rate
    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

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 399 400
    OS Rate at Year 1
    46.5
    11.7%
    40.8
    10.2%
    OS Rate at Year 2
    25.2
    6.3%
    16.6
    4.2%
    OS Rate at Year 3
    15.3
    3.8%
    7.9
    2%
    OS Rate at Year 4
    10.1
    2.5%
    3.3
    0.8%
    OS Rate at Year 5
    7.9
    2%
    2.7
    0.7%
    3. Secondary Outcome
    Title Progression Free Survival (PFS)
    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

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 399 400
    Median (95% Confidence Interval) [months]
    4.01
    3.06
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab + Radiotherapy, Placebo + Radiotherapy
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.70
    Confidence Interval (2-Sided) 95%
    0.61 to 0.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments Ipilimumab over placebo
    4. Secondary Outcome
    Title Pain Response
    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

    Outcome Measure Data

    Analysis Population Description
    All pain-evaluable participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 197 186
    Number (95% Confidence Interval) [percentage of participants]
    3.55
    0.9%
    0.54
    0.1%
    5. Secondary Outcome
    Title Duration of Pain Response
    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

    Outcome Measure Data

    Analysis Population Description
    All pain-evaluable participants with pain response
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 7 1
    Median (95% Confidence Interval) [months]
    2.5
    1.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ipilimumab + Radiotherapy, Placebo + Radiotherapy
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.25
    Confidence Interval (2-Sided) 95%
    0.02 to 4.00
    Parameter Dispersion Type:
    Value:
    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)
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 393 396
    SAE
    257
    64.4%
    164
    41%
    Treatment-Related AE
    296
    74.2%
    180
    45%
    Any Death
    346
    86.7%
    371
    92.8%
    Deaths Due to Study Drug Toxicity
    7
    1.8%
    1
    0.3%
    Discontinuation of Study Drug due to AEs
    137
    34.3%
    62
    15.5%
    Immune-Related AE (any grade)
    250
    62.7%
    86
    21.5%
    Immune-Mediated Adverse Reaction (Grade >=2)
    203
    50.9%
    40
    10%
    7. Secondary Outcome
    Title Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE)
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 393 396
    Gastrotintestinal (n= 71,3)
    5.71
    5.71
    Liver (n= 18,5)
    9.14
    6.00
    Skin (n=4,0)
    3.71
    NA
    Endocrine (n=8,2)
    7.93
    5.00
    Neurological (n= 1,0)
    11.4
    NA
    8. Secondary Outcome
    Title Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE)
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 393 396
    Gastrointestinal (n=71,3)
    2.9
    0.9
    Liver (n=18,5)
    4.1
    6.0
    Skin (n=4,0)
    3.6
    NA
    Endocrine (n=8,2)
    11.1
    5.9
    Neurological (n=1,0)
    NA
    NA
    9. Secondary Outcome
    Title Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR)
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants receiving Ipilimumab + Radiotherapy
    Arm/Group Title Ipilimumab + Radiotherapy
    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.
    Measure Participants 393
    Enterocolitis (n=65)
    3.4
    Hepatitis (n=17)
    9.0
    Dermatitis (n=3)
    2.4
    Endocrinopathies (n=6)
    7.9
    10. Secondary Outcome
    Title Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants receiving Ipilimumab + Radiotherapy
    Arm/Group Title Ipilimumab + Radiotherapy
    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.
    Measure Participants 393
    Enterocolitis (n=52)
    6.0
    Hepatitis (n=15)
    8.6
    Dermatitis (n=3)
    6.9
    Endocrinopathies (n=0)
    NA
    11. Secondary Outcome
    Title Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 393 396
    WBC Gr 0 at Baseline to Gr 3-4
    3
    0.8%
    2
    0.5%
    WBC Gr 1 at Baseline to Gr 3-4
    0
    0%
    1
    0.3%
    WBC Gr 2 at Baseline to Gr 3-4
    0
    0%
    1
    0.3%
    WBC Gr 3 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    WBC Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    WBC Not Reported at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ANC Gr 0 at Baseline to Gr 3-4
    4
    1%
    6
    1.5%
    ANC Gr 1 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ANC Gr 2 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ANC Gr 3 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ANC Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ANC Not Reported at Baseline to Gr 3-4
    1
    0.3%
    0
    0%
    Platelet Count Gr 0 at Baseline to Gr 3-4
    1
    0.3%
    6
    1.5%
    Platelet Count Gr 1 at Baseline to Gr 3-4
    1
    0.3%
    1
    0.3%
    Platelet Count Gr 2 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Platelet Count Gr 3 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Platelet Count Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Platelet Count Not Reported at Baseline to Gr 3-4
    1
    0.3%
    1
    0.3%
    Hemoglobin Gr 0 at Baseline to Gr 3-4
    0
    0%
    3
    0.8%
    Hemoglobin Gr 1 at Baseline to Gr 3-4
    16
    4%
    25
    6.3%
    Hemoglobin Gr 2 at Baseline to Gr 3-4
    13
    3.3%
    11
    2.8%
    Hemoglobin Gr 3 at Baseline to Gr 3-4
    0
    0%
    1
    0.3%
    Hemoglobin Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Hemoglobin Not Reported at Baseline to Gr 3-4
    0
    0%
    1
    0.3%
    Lymphocytes Gr 0 at Baseline to Gr 3-4
    4
    1%
    1
    0.3%
    Lymphocytes Gr 1 at Baseline to Gr 3-4
    6
    1.5%
    11
    2.8%
    Lymphocytes Gr 2 at Baseline to Gr 3-4
    11
    2.8%
    17
    4.3%
    Lymphocytes Gr 3 at Baseline to Gr 3-4
    8
    2%
    7
    1.8%
    Lymphocytes Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Lymphocytes Not Reported at Baseline to Gr 3-4
    3
    0.8%
    0
    0%
    12. Secondary Outcome
    Title Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 393 396
    ALT Gr 0 at Baseline to Gr 3-4
    16
    4%
    1
    0.3%
    ALT Gr 1 at Baseline to Gr 3-4
    1
    0.3%
    1
    0.3%
    ALT Gr 2 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ALT Gr 3 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ALT Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ALT Not reported at Basline to Gr 3-4
    1
    0.3%
    0
    0%
    AST Gr 0 at Baseline to Gr 3-4
    15
    3.8%
    6
    1.5%
    AST Gr 1 at Baseline to Gr 3-4
    5
    1.3%
    1
    0.3%
    AST Gr 2 at Baseline to Gr 3-4
    1
    0.3%
    1
    0.3%
    AST Gr 3 at Baseline to Gr 3-4
    1
    0.3%
    0
    0%
    AST Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    AST Not Reported at Baseline to Gr 3-4
    1
    0.3%
    0
    0%
    Total Bilirubin Gr 0 at Baseline to Gr 3-4
    6
    1.5%
    2
    0.5%
    Total Bilirubin Gr 1 at Baseline to Gr 3-4
    1
    0.3%
    0
    0%
    Total Bilirubin Gr 2 at Baseline to Gr 3-4
    1
    0.3%
    0
    0%
    Total Bilirubin Gr 3 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Total Bilirubin Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Total Bilirubin Not Reported at Baseline to Gr 3-4
    0
    0%
    0
    0%
    ALP Gr 0 at Baseline to Gr 3-4
    1
    0.3%
    1
    0.3%
    ALP Gr 1 at Baseline to Gr 3-4
    10
    2.5%
    17
    4.3%
    ALP Gr 2 at Baseline to Gr 3-4
    21
    5.3%
    29
    7.3%
    ALP Gr 3 at Baseline to Gr 3-4
    27
    6.8%
    42
    10.5%
    ALP Gr 4 at Baseline to Gr 3-4
    1
    0.3%
    0
    0%
    ALP Not Reported at Baseline to Gr 3-4
    0
    0%
    6
    1.5%
    13. Secondary Outcome
    Title Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 393 396
    Lipase Gr 0 at Baseline to Gr 3-4
    21
    5.3%
    10
    2.5%
    Lipase Gr 1 at Baseline to Gr 3-4
    1
    0.3%
    1
    0.3%
    Lipase Gr 2 at Baseline to Gr 3-4
    1
    0.3%
    0
    0%
    Lipase Gr 3 at Baseline to Gr 3-4
    0
    0%
    1
    0.3%
    Lipase Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Lipase Not reported at Basline to Gr 3-4
    0
    0%
    0
    0%
    Amylase Gr 0 at Baseline to Gr 3-4
    4
    1%
    4
    1%
    Amylase Gr 1 at Baseline to Gr 3-4
    1
    0.3%
    1
    0.3%
    Amylase Gr 2 at Baseline to Gr 3-4
    3
    0.8%
    1
    0.3%
    Amylase Gr 3 at Baseline to Gr 3-4
    1
    0.3%
    0
    0%
    Amylase Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Amylase Not Reported at Baseline to Gr 3-4
    0
    0%
    0
    0%
    14. Secondary Outcome
    Title Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline
    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

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Ipilimumab + Radiotherapy Placebo + Radiotherapy
    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.
    Measure Participants 393 396
    Creatinine Gr 0 at Baseline to Gr 3-4
    3
    0.8%
    3
    0.8%
    Creatinine Gr 1 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Creatinine Gr 2 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Creatinine Gr 3 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Creatinine Gr 4 at Baseline to Gr 3-4
    0
    0%
    0
    0%
    Creatinine Not Reported at Baseline to Gr 3-4
    0
    0%
    0
    0%

    Adverse Events

    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
    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 (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Ipilimumab + Radiotherapy Placebo + Radiotherapy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 257/393 (65.4%) 164/396 (41.4%)
    Blood and lymphatic system disorders
    Anaemia of malignant disease 0/393 (0%) 1/396 (0.3%)
    Leukopenia 1/393 (0.3%) 1/396 (0.3%)
    Thrombocytopenia 1/393 (0.3%) 6/396 (1.5%)
    Anaemia 15/393 (3.8%) 18/396 (4.5%)
    Febrile neutropenia 2/393 (0.5%) 1/396 (0.3%)
    Cardiac disorders
    Myocardial ischaemia 1/393 (0.3%) 0/396 (0%)
    Pericardial effusion 1/393 (0.3%) 0/396 (0%)
    Cardio-respiratory arrest 2/393 (0.5%) 2/396 (0.5%)
    Myocardial infarction 1/393 (0.3%) 1/396 (0.3%)
    Acute myocardial infarction 2/393 (0.5%) 1/396 (0.3%)
    Cardiac failure congestive 0/393 (0%) 1/396 (0.3%)
    Bradycardia 1/393 (0.3%) 0/396 (0%)
    Cardiac failure 2/393 (0.5%) 1/396 (0.3%)
    Atrial fibrillation 2/393 (0.5%) 2/396 (0.5%)
    Cardiac valve disease 0/393 (0%) 1/396 (0.3%)
    Cardiopulmonary failure 1/393 (0.3%) 1/396 (0.3%)
    Arrhythmia 3/393 (0.8%) 0/396 (0%)
    Cardiac arrest 2/393 (0.5%) 0/396 (0%)
    Cardiac failure acute 1/393 (0.3%) 0/396 (0%)
    Tachycardia 2/393 (0.5%) 0/396 (0%)
    Endocrine disorders
    Adrenocorticotropic hormone deficiency 1/393 (0.3%) 0/396 (0%)
    Hyperthyroidism 4/393 (1%) 0/396 (0%)
    Hypophysitis 2/393 (0.5%) 2/396 (0.5%)
    Hypothyroidism 2/393 (0.5%) 0/396 (0%)
    Adrenal insufficiency 2/393 (0.5%) 1/396 (0.3%)
    Hypopituitarism 3/393 (0.8%) 0/396 (0%)
    Eye disorders
    Pupils unequal 0/393 (0%) 1/396 (0.3%)
    Retinal vein thrombosis 0/393 (0%) 1/396 (0.3%)
    Papilloedema 0/393 (0%) 1/396 (0.3%)
    Macular degeneration 0/393 (0%) 1/396 (0.3%)
    Gastrointestinal disorders
    Colitis ulcerative 2/393 (0.5%) 0/396 (0%)
    Large intestine perforation 2/393 (0.5%) 0/396 (0%)
    Proctalgia 0/393 (0%) 1/396 (0.3%)
    Small intestinal obstruction 0/393 (0%) 1/396 (0.3%)
    Abdominal pain 4/393 (1%) 5/396 (1.3%)
    Colitis 21/393 (5.3%) 0/396 (0%)
    Femoral hernia incarcerated 0/393 (0%) 1/396 (0.3%)
    Gastric ulcer 1/393 (0.3%) 0/396 (0%)
    Gastrointestinal obstruction 1/393 (0.3%) 1/396 (0.3%)
    Gastrointestinal pain 0/393 (0%) 1/396 (0.3%)
    Diverticular perforation 1/393 (0.3%) 0/396 (0%)
    Proctitis 1/393 (0.3%) 0/396 (0%)
    Dysphagia 0/393 (0%) 1/396 (0.3%)
    Enterocolitis haemorrhagic 1/393 (0.3%) 0/396 (0%)
    Ileus 1/393 (0.3%) 0/396 (0%)
    Intestinal haemorrhage 2/393 (0.5%) 0/396 (0%)
    Nausea 11/393 (2.8%) 8/396 (2%)
    Oesophageal perforation 1/393 (0.3%) 0/396 (0%)
    Abdominal distension 1/393 (0.3%) 1/396 (0.3%)
    Diarrhoea 59/393 (15%) 6/396 (1.5%)
    Duodenitis 1/393 (0.3%) 0/396 (0%)
    Enteritis 1/393 (0.3%) 0/396 (0%)
    Gastritis 1/393 (0.3%) 0/396 (0%)
    Gastrointestinal disorder 1/393 (0.3%) 0/396 (0%)
    Haematemesis 0/393 (0%) 1/396 (0.3%)
    Rectal haemorrhage 1/393 (0.3%) 1/396 (0.3%)
    Constipation 7/393 (1.8%) 3/396 (0.8%)
    Intestinal obstruction 1/393 (0.3%) 0/396 (0%)
    Vomiting 11/393 (2.8%) 10/396 (2.5%)
    Abdominal pain upper 1/393 (0.3%) 0/396 (0%)
    Abdominal pain lower 0/393 (0%) 1/396 (0.3%)
    Chronic gastritis 1/393 (0.3%) 0/396 (0%)
    Gastrointestinal haemorrhage 2/393 (0.5%) 0/396 (0%)
    Melaena 2/393 (0.5%) 0/396 (0%)
    General disorders
    Device malfunction 1/393 (0.3%) 0/396 (0%)
    General physical health deterioration 16/393 (4.1%) 8/396 (2%)
    Malaise 7/393 (1.8%) 1/396 (0.3%)
    Mucosal inflammation 1/393 (0.3%) 0/396 (0%)
    Fatigue 13/393 (3.3%) 10/396 (2.5%)
    Oedema peripheral 1/393 (0.3%) 0/396 (0%)
    Pyrexia 17/393 (4.3%) 2/396 (0.5%)
    Peripheral swelling 0/393 (0%) 1/396 (0.3%)
    Chest pain 2/393 (0.5%) 3/396 (0.8%)
    Chills 2/393 (0.5%) 0/396 (0%)
    Asthenia 9/393 (2.3%) 4/396 (1%)
    Pain 6/393 (1.5%) 10/396 (2.5%)
    Performance status decreased 1/393 (0.3%) 0/396 (0%)
    Death 2/393 (0.5%) 1/396 (0.3%)
    Multi-organ failure 2/393 (0.5%) 4/396 (1%)
    Hepatobiliary disorders
    Hepatitis 4/393 (1%) 0/396 (0%)
    Cholecystitis acute 1/393 (0.3%) 0/396 (0%)
    Hepatic failure 1/393 (0.3%) 0/396 (0%)
    Cholecystitis 2/393 (0.5%) 0/396 (0%)
    Hepatotoxicity 1/393 (0.3%) 0/396 (0%)
    Autoimmune hepatitis 1/393 (0.3%) 0/396 (0%)
    Cholangitis 1/393 (0.3%) 0/396 (0%)
    Cholecystitis chronic 1/393 (0.3%) 0/396 (0%)
    Jaundice cholestatic 0/393 (0%) 1/396 (0.3%)
    Immune system disorders
    Hypersensitivity 2/393 (0.5%) 0/396 (0%)
    Autoimmune disorder 1/393 (0.3%) 0/396 (0%)
    Infections and infestations
    Cellulitis 1/393 (0.3%) 2/396 (0.5%)
    Epstein-Barr virus infection 1/393 (0.3%) 0/396 (0%)
    Central nervous system infection 0/393 (0%) 1/396 (0.3%)
    Pneumonia 18/393 (4.6%) 5/396 (1.3%)
    Anal abscess 0/393 (0%) 1/396 (0.3%)
    Cavernous sinus thrombosis 0/393 (0%) 1/396 (0.3%)
    Febrile infection 1/393 (0.3%) 0/396 (0%)
    Labyrinthitis 1/393 (0.3%) 0/396 (0%)
    Lower respiratory tract infection 1/393 (0.3%) 0/396 (0%)
    Streptococcal bacteraemia 1/393 (0.3%) 0/396 (0%)
    Viral infection 0/393 (0%) 1/396 (0.3%)
    Anal infection 1/393 (0.3%) 0/396 (0%)
    Bacterial sepsis 0/393 (0%) 1/396 (0.3%)
    Gastroenteritis 2/393 (0.5%) 0/396 (0%)
    Herpes zoster 1/393 (0.3%) 1/396 (0.3%)
    Lobar pneumonia 1/393 (0.3%) 1/396 (0.3%)
    Periorbital cellulitis 1/393 (0.3%) 0/396 (0%)
    Septic shock 1/393 (0.3%) 0/396 (0%)
    Spinal cord infection 0/393 (0%) 1/396 (0.3%)
    Bronchopneumonia 0/393 (0%) 3/396 (0.8%)
    Gastroenteritis viral 1/393 (0.3%) 0/396 (0%)
    Lung infection 1/393 (0.3%) 0/396 (0%)
    Subcutaneous abscess 2/393 (0.5%) 0/396 (0%)
    Urinary tract infection 12/393 (3.1%) 4/396 (1%)
    Cystitis 1/393 (0.3%) 0/396 (0%)
    Escherichia urinary tract infection 0/393 (0%) 1/396 (0.3%)
    Respiratory tract infection 2/393 (0.5%) 1/396 (0.3%)
    Urosepsis 0/393 (0%) 1/396 (0.3%)
    Bronchitis bacterial 0/393 (0%) 1/396 (0.3%)
    Infection 2/393 (0.5%) 2/396 (0.5%)
    Pyelonephritis 1/393 (0.3%) 0/396 (0%)
    Sepsis 6/393 (1.5%) 3/396 (0.8%)
    Injury, poisoning and procedural complications
    Fall 1/393 (0.3%) 0/396 (0%)
    Humerus fracture 1/393 (0.3%) 0/396 (0%)
    Fracture 2/393 (0.5%) 0/396 (0%)
    Toxicity to various agents 1/393 (0.3%) 0/396 (0%)
    Hip fracture 1/393 (0.3%) 0/396 (0%)
    Femoral neck fracture 0/393 (0%) 1/396 (0.3%)
    Ankle fracture 1/393 (0.3%) 0/396 (0%)
    Bone fissure 1/393 (0.3%) 0/396 (0%)
    Subdural haematoma 2/393 (0.5%) 2/396 (0.5%)
    Femur fracture 1/393 (0.3%) 0/396 (0%)
    Investigations
    Blood bilirubin increased 1/393 (0.3%) 0/396 (0%)
    Blood creatine phosphokinase increased 1/393 (0.3%) 0/396 (0%)
    Blood creatinine increased 3/393 (0.8%) 1/396 (0.3%)
    C-reactive protein increased 1/393 (0.3%) 0/396 (0%)
    Liver function test abnormal 3/393 (0.8%) 0/396 (0%)
    Red blood cell count decreased 0/393 (0%) 1/396 (0.3%)
    Aspartate aminotransferase increased 7/393 (1.8%) 0/396 (0%)
    Eastern Cooperative Oncology Group performance status worsened 0/393 (0%) 2/396 (0.5%)
    Haemoglobin decreased 13/393 (3.3%) 7/396 (1.8%)
    Blood creatine phosphokinase decreased 1/393 (0.3%) 0/396 (0%)
    Platelet count decreased 0/393 (0%) 2/396 (0.5%)
    Alanine aminotransferase increased 6/393 (1.5%) 0/396 (0%)
    General physical condition abnormal 0/393 (0%) 2/396 (0.5%)
    Weight decreased 2/393 (0.5%) 0/396 (0%)
    Metabolism and nutrition disorders
    Dehydration 18/393 (4.6%) 10/396 (2.5%)
    Decreased appetite 3/393 (0.8%) 2/396 (0.5%)
    Hypokalaemia 2/393 (0.5%) 0/396 (0%)
    Hyponatraemia 3/393 (0.8%) 0/396 (0%)
    Failure to thrive 1/393 (0.3%) 0/396 (0%)
    Hypocalcaemia 3/393 (0.8%) 1/396 (0.3%)
    Hyperglycaemia 0/393 (0%) 1/396 (0.3%)
    Hypoglycaemia 0/393 (0%) 1/396 (0.3%)
    Tumour lysis syndrome 1/393 (0.3%) 0/396 (0%)
    Musculoskeletal and connective tissue disorders
    Flank pain 0/393 (0%) 1/396 (0.3%)
    Musculoskeletal pain 0/393 (0%) 5/396 (1.3%)
    Spinal pain 0/393 (0%) 1/396 (0.3%)
    Pathological fracture 1/393 (0.3%) 0/396 (0%)
    Groin pain 0/393 (0%) 1/396 (0.3%)
    Musculoskeletal chest pain 1/393 (0.3%) 0/396 (0%)
    Neck pain 1/393 (0.3%) 1/396 (0.3%)
    Pain in extremity 3/393 (0.8%) 2/396 (0.5%)
    Muscular weakness 5/393 (1.3%) 0/396 (0%)
    Arthralgia 2/393 (0.5%) 2/396 (0.5%)
    Back pain 7/393 (1.8%) 8/396 (2%)
    Bone pain 4/393 (1%) 4/396 (1%)
    Myalgia 0/393 (0%) 1/396 (0.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/393 (0%) 1/396 (0.3%)
    Plasma cell myeloma 0/393 (0%) 1/396 (0.3%)
    Cerebellopontine angle tumour 1/393 (0.3%) 0/396 (0%)
    Metastases to central nervous system 0/393 (0%) 2/396 (0.5%)
    Prostate cancer 1/393 (0.3%) 0/396 (0%)
    Lymphangiosis carcinomatosa 1/393 (0.3%) 0/396 (0%)
    Malignant neoplasm of spinal cord 1/393 (0.3%) 0/396 (0%)
    Metastases to bone 1/393 (0.3%) 1/396 (0.3%)
    Malignant neoplasm progression 36/393 (9.2%) 31/396 (7.8%)
    Tumour pain 1/393 (0.3%) 1/396 (0.3%)
    Prostate cancer metastatic 1/393 (0.3%) 0/396 (0%)
    Nervous system disorders
    Headache 1/393 (0.3%) 3/396 (0.8%)
    Paraparesis 1/393 (0.3%) 1/396 (0.3%)
    Lethargy 2/393 (0.5%) 1/396 (0.3%)
    Trigeminal nerve disorder 0/393 (0%) 1/396 (0.3%)
    Central nervous system haemorrhage 0/393 (0%) 2/396 (0.5%)
    Cerebrovascular accident 3/393 (0.8%) 2/396 (0.5%)
    Dizziness 1/393 (0.3%) 1/396 (0.3%)
    Neurological symptom 0/393 (0%) 1/396 (0.3%)
    Paresis 0/393 (0%) 1/396 (0.3%)
    Cerebral haematoma 1/393 (0.3%) 0/396 (0%)
    Cerebral haemorrhage 2/393 (0.5%) 0/396 (0%)
    Cerebral infarction 0/393 (0%) 1/396 (0.3%)
    Cerebral ischaemia 1/393 (0.3%) 0/396 (0%)
    Hypoaesthesia 0/393 (0%) 1/396 (0.3%)
    Peripheral motor neuropathy 4/393 (1%) 1/396 (0.3%)
    Haemorrhage intracranial 0/393 (0%) 1/396 (0.3%)
    Spinal cord compression 4/393 (1%) 2/396 (0.5%)
    Epilepsy 0/393 (0%) 1/396 (0.3%)
    Tongue paralysis 0/393 (0%) 1/396 (0.3%)
    Cerebrovascular disorder 0/393 (0%) 1/396 (0.3%)
    Depressed level of consciousness 1/393 (0.3%) 0/396 (0%)
    Peripheral sensory neuropathy 0/393 (0%) 2/396 (0.5%)
    Syncope 1/393 (0.3%) 2/396 (0.5%)
    Brachial plexopathy 0/393 (0%) 1/396 (0.3%)
    Paraesthesia 0/393 (0%) 1/396 (0.3%)
    Paraplegia 0/393 (0%) 1/396 (0.3%)
    Seizure 1/393 (0.3%) 0/396 (0%)
    Somnolence 1/393 (0.3%) 1/396 (0.3%)
    Subarachnoid haemorrhage 0/393 (0%) 1/396 (0.3%)
    Psychiatric disorders
    Depression 1/393 (0.3%) 0/396 (0%)
    Hallucination 1/393 (0.3%) 0/396 (0%)
    Self injurious behaviour 1/393 (0.3%) 0/396 (0%)
    Anxiety 0/393 (0%) 1/396 (0.3%)
    Confusional state 3/393 (0.8%) 3/396 (0.8%)
    Renal and urinary disorders
    Acute prerenal failure 0/393 (0%) 1/396 (0.3%)
    Urinary tract obstruction 1/393 (0.3%) 0/396 (0%)
    Hydronephrosis 2/393 (0.5%) 3/396 (0.8%)
    Renal impairment 1/393 (0.3%) 2/396 (0.5%)
    Bladder dilatation 1/393 (0.3%) 0/396 (0%)
    Bladder obstruction 1/393 (0.3%) 0/396 (0%)
    Nephrolithiasis 1/393 (0.3%) 0/396 (0%)
    Renal injury 1/393 (0.3%) 0/396 (0%)
    Ureteric obstruction 2/393 (0.5%) 0/396 (0%)
    Anuria 0/393 (0%) 1/396 (0.3%)
    Renal failure 4/393 (1%) 1/396 (0.3%)
    Acute kidney injury 7/393 (1.8%) 2/396 (0.5%)
    Haematuria 6/393 (1.5%) 6/396 (1.5%)
    Urinary retention 2/393 (0.5%) 2/396 (0.5%)
    Urethral obstruction 0/393 (0%) 1/396 (0.3%)
    Respiratory, thoracic and mediastinal disorders
    Lung infiltration 1/393 (0.3%) 0/396 (0%)
    Acute respiratory failure 0/393 (0%) 1/396 (0.3%)
    Dyspnoea 8/393 (2%) 6/396 (1.5%)
    Pneumonitis 1/393 (0.3%) 0/396 (0%)
    Aspiration 1/393 (0.3%) 0/396 (0%)
    Epistaxis 0/393 (0%) 1/396 (0.3%)
    Acute pulmonary oedema 2/393 (0.5%) 0/396 (0%)
    Lung disorder 0/393 (0%) 1/396 (0.3%)
    Pleural effusion 4/393 (1%) 6/396 (1.5%)
    Pulmonary embolism 3/393 (0.8%) 4/396 (1%)
    Pulmonary hypertension 0/393 (0%) 1/396 (0.3%)
    Pulmonary oedema 1/393 (0.3%) 0/396 (0%)
    Bronchospasm 1/393 (0.3%) 1/396 (0.3%)
    Hypoxia 0/393 (0%) 1/396 (0.3%)
    Respiratory failure 0/393 (0%) 1/396 (0.3%)
    Pneumonia aspiration 2/393 (0.5%) 0/396 (0%)
    Skin and subcutaneous tissue disorders
    Rash 3/393 (0.8%) 1/396 (0.3%)
    Hyperhidrosis 0/393 (0%) 1/396 (0.3%)
    Vascular disorders
    Hypovolaemic shock 1/393 (0.3%) 1/396 (0.3%)
    Venous thrombosis 1/393 (0.3%) 0/396 (0%)
    Deep vein thrombosis 1/393 (0.3%) 2/396 (0.5%)
    Hypertensive crisis 1/393 (0.3%) 0/396 (0%)
    Peripheral ischaemia 0/393 (0%) 1/396 (0.3%)
    Thrombosis 1/393 (0.3%) 0/396 (0%)
    Hypotension 3/393 (0.8%) 1/396 (0.3%)
    Vasculitis 1/393 (0.3%) 0/396 (0%)
    Other (Not Including Serious) Adverse Events
    Ipilimumab + Radiotherapy Placebo + Radiotherapy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 350/393 (89.1%) 333/396 (84.1%)
    Blood and lymphatic system disorders
    Anaemia 79/393 (20.1%) 81/396 (20.5%)
    Gastrointestinal disorders
    Abdominal pain 33/393 (8.4%) 25/396 (6.3%)
    Nausea 126/393 (32.1%) 104/396 (26.3%)
    Diarrhoea 186/393 (47.3%) 94/396 (23.7%)
    Constipation 66/393 (16.8%) 82/396 (20.7%)
    Vomiting 107/393 (27.2%) 80/396 (20.2%)
    General disorders
    Fatigue 144/393 (36.6%) 120/396 (30.3%)
    Oedema peripheral 46/393 (11.7%) 33/396 (8.3%)
    Pyrexia 81/393 (20.6%) 50/396 (12.6%)
    Asthenia 80/393 (20.4%) 64/396 (16.2%)
    Pain 33/393 (8.4%) 44/396 (11.1%)
    Infections and infestations
    Urinary tract infection 24/393 (6.1%) 24/396 (6.1%)
    Investigations
    Aspartate aminotransferase increased 31/393 (7.9%) 21/396 (5.3%)
    Haemoglobin decreased 26/393 (6.6%) 20/396 (5.1%)
    Alanine aminotransferase increased 26/393 (6.6%) 9/396 (2.3%)
    Weight decreased 91/393 (23.2%) 56/396 (14.1%)
    Metabolism and nutrition disorders
    Dehydration 26/393 (6.6%) 15/396 (3.8%)
    Decreased appetite 119/393 (30.3%) 97/396 (24.5%)
    Hypokalaemia 20/393 (5.1%) 10/396 (2.5%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain 32/393 (8.1%) 44/396 (11.1%)
    Pain in extremity 31/393 (7.9%) 41/396 (10.4%)
    Arthralgia 44/393 (11.2%) 57/396 (14.4%)
    Back pain 56/393 (14.2%) 74/396 (18.7%)
    Bone pain 31/393 (7.9%) 53/396 (13.4%)
    Nervous system disorders
    Headache 38/393 (9.7%) 31/396 (7.8%)
    Dizziness 22/393 (5.6%) 18/396 (4.5%)
    Psychiatric disorders
    Depression 10/393 (2.5%) 20/396 (5.1%)
    Insomnia 31/393 (7.9%) 34/396 (8.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 36/393 (9.2%) 27/396 (6.8%)
    Dyspnoea 47/393 (12%) 32/396 (8.1%)
    Skin and subcutaneous tissue disorders
    Pruritus 99/393 (25.2%) 22/396 (5.6%)
    Rash 81/393 (20.6%) 27/396 (6.8%)
    Vascular disorders
    Hypertension 20/393 (5.1%) 13/396 (3.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00861614
    Other Study ID Numbers:
    • CA184-043
    • 2008-003314-97
    First Posted:
    Mar 13, 2009
    Last Update Posted:
    Sep 30, 2016
    Last Verified:
    Aug 1, 2016