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Trial record 71 of 518 for:    melanoma phase III

Efficacy Study of Ipilimumab Versus Placebo to Prevent Recurrence After Complete Resection of High Risk Stage III Melanoma

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ClinicalTrials.gov Identifier: NCT00636168
Recruitment Status : Unknown
Verified October 2017 by Bristol-Myers Squibb.
Recruitment status was:  Active, not recruiting
First Posted : March 14, 2008
Results First Posted : August 19, 2014
Last Update Posted : November 6, 2017
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition High Risk Stage III Melanoma
Interventions Drug: ipilimumab
Drug: Placebo
Enrollment 1211
Recruitment Details Study initiated 24 June 2008; Primary endpoint achieved 26 July 2013; Study currently ongoing. Primary endpoint was recurrence-free survival and was analyzed when 528 actual events (event=first recurrence of disease or death) were reported.
Pre-assignment Details 1211 enrolled/screened; 951 randomized to treatment. Reasons for not being randomized to a treatment arm: 193 screen failures, 42 participants refused, 19 were not randomized within 12 weeks from the last surgery that made the participant free of disease, 6 had other non-specified reasons.
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg, by IV infusion, every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed. Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Period Title: Randomized to Study Drug
Started 475 476
Completed 471 474
Not Completed 4 2
Reason Not Completed
Withdrawal by Subject             2             2
Adverse Event             1             0
No longer met study criteria             1             0
Period Title: Treated With Study Drug
Started 471 474
Completed 24 63
Not Completed 447 411
Reason Not Completed
Recurrence of disease             132             273
Adverse Event             244             20
Withdrawal by Subject             16             20
Poor or non-compliance             1             3
Death             3             0
Pregnancy             1             0
No longer meets criteria             1             0
non-specified             1             1
Still remains on treatment             48             94
Arm/Group Title Ipilimumab 10mg/kg Placebo Total
Hide Arm/Group Description Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg by IV infusion, every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed. Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed. Total of all reporting groups
Overall Number of Baseline Participants 475 476 951
Hide Baseline Analysis Population Description
All participants randomized to a study arm (Intent to treat population) were analyzed in the arm to which they were allocated by randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 475 participants 476 participants 951 participants
50.7  (12.90) 51.5  (12.82) 51.1  (12.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
Female
179
  37.7%
183
  38.4%
362
  38.1%
Male
296
  62.3%
293
  61.6%
589
  61.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   0.2%
0
   0.0%
1
   0.1%
Native Hawaiian or Other Pacific Islander
1
   0.2%
0
   0.0%
1
   0.1%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
470
  98.9%
476
 100.0%
946
  99.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   0.6%
0
   0.0%
3
   0.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
United States 108 104 212
Finland 5 6 11
Spain 5 6 11
Austria 3 6 9
Russian Federation 27 27 54
Switzerland 22 19 41
Italy 72 72 144
United Kingdom 19 17 36
France 71 73 144
Czech Republic 10 10 20
Canada 11 13 24
Belgium 7 9 16
Poland 5 6 11
Denmark 30 29 59
Australia 19 18 37
Netherlands 11 12 23
Germany 39 38 77
Norway 5 6 11
Sweden 6 5 11
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
ECOG PS 0 445 448 893
ECOG PS 1 29 28 57
ECOG PS 2 1 0 1
[1]
Measure Description: ECOG performance: 0= Fully active, able to carry on all pre-disease performance without restriction;1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2=Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or Chair; 5=Dead
Stage at Study Entry   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
Stage IIIa 98 88 186
Stage IIIb 213 207 420
Stage IIIc with 1-3 positive lymph nodes 69 83 152
Stage IIIc with >=4 positive lymph nodes 95 98 193
[1]
Measure Description: According to American Joint Committee on Cancer (AJCC 2002) Classification, the stage III TNM System was defined at baseline based on the number of metastatic nodes (1, 2-3, > or =4), the type of lymph node involvement (micro- vs. macrometastasis) (N1, 2 or 3) and the ulceration status of the tumor (Ta or Tb). Once the T and N are determined in the absence of distant metastasis (M0), they are combined, and a stage of IIIA, IIIB or IIIC is assigned based on the combination.
Breslow's Thickness   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
<= 1 mm 60 70 130
>1 to <= 2 mm 120 135 255
>2 to <= 4 mm 164 132 296
> 4 mm 114 112 226
Not Reported 17 27 44
[1]
Measure Description: Breslow's Thickness is a measure of the vertical thickness of a cutaneous melanoma lesion and is reported in millimeters (mm).
Ulceration of Primary Tumor   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
Ulceration Absent 257 244 501
Ulceration Present 197 203 400
Ulceration Unknown 21 29 50
[1]
Measure Description: Ulceration of the primary tumor is taken into consideration in determining what Tumor Node Metastasis (TMN) stage a tumor is classified.
Category of Regional Lymph Node Classification   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
N0 0 0 0
N1 217 220 437
N2 163 158 321
N3 95 98 193
[1]
Measure Description: AJCC classification of regional lymph nodes: NX=Cannot be assessed; N0=No lymph node metastasis; N1=Metastasis to 1 lymph node; N2=Metastasis to 2 or 3 nodes or intralymphatic regional metastasis without nodal metastases; N3=Metastasis in more than 4 regional nodes, or matted lymph nodes, or intransit metastasis or satellite(s) with metastatic regional node(s)
Lymph Node Involvement   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 475 participants 476 participants 951 participants
Microscopic 210 193 403
Macroscopic 265 283 548
[1]
Measure Description: AJCC classification of regional lymph nodes: Clinically occult (microscopic) metastasis and Clinically palpable (macroscopic) metastasis.
1.Primary Outcome
Title Recurrence Free Survival (RFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
Hide Description Recurrence free survival (RFS) was programmatically determined based on the disease recurrence data provided by the IRC and was defined as the time between the date of randomization and the date of first recurrence or death (whatever the cause), whichever occurred first. A patient who died without reported recurrence was considered to have recurrence on the date of death. For those patients who remained alive and recurrence-free, RFS was censored on the date of last evaluable post-randomization tumor assessment. For those who remained alive and had no recorded post-randomization tumor assessment, RFS was censored on the day of randomization. Patients with disease at baseline were considered to have an event on the day of randomization. Computerized tomography (CT) and magnetic resonance imaging (MRI) were mandatory to establish recurrence. The primary analysis was event-driven and planned when at least 512 RFS events assessed per IRC were collected.
Time Frame Date of randomization to first date of recurrence or death or last available disease assessment with RFS data up to 5 years. Median follow-up was 2.7 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients (ITT), analyzed in the arm to which they were allocated by randomization were analyzed.
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description:
Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg by IV infusion, every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Overall Number of Participants Analyzed 475 476
Median (95% Confidence Interval)
Unit of Measure: months
26.09
(19.32 to 39.26)
17.05
(13.40 to 21.62)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ipilimumab 10mg/kg, Placebo
Comments The hazard ratio, and its 95 % confidence interval was estimated using a Cox proportional hazards model, stratified by stage (IIIa vs. IIIb vs. IIIc with 1-3 positive lymph-nodes vs. IIIc with >= 4 positive lymph-nodes) as indicated at randomization, with treatment as the single covariate.. The analysis was performed after 528 RFS events per IRC were reported. Two-sided, 95% confidence intervals for median RFS were computed by the Brookmeyer and Crowley method using log-log transformation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.64 to 0.90
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Patients With Recurrence or Death as Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
Time Frame Date of randomization to first date of recurrence or death or last available disease assessment with RFS data upto 5 years. Median follow-up was 2.7 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients (ITT), analyzed in the arm to which they were allocated by randomization were analyzed.
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description:
Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg, by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Overall Number of Participants Analyzed 475 476
Measure Type: Number
Unit of Measure: participants
234 294
3.Primary Outcome
Title Recurrence-Free Survival (RFS) Rates Per IRC at 1 Year, 2 Years, and 3 Years in the ITT Population
Hide Description RFS was defined as the time between the date of randomization and the date of first recurrence or death (whatever the cause), whichever occurred first. A patient who died without reported recurrence was considered to have recurrence on the date of death. For those who remained alive and recurrence-free, RFS was censored on the date of last evaluable post-randomization tumor assessment. For those who remained alive and had no recorded post-randomization tumor assessment, RFS was censored on the day of randomization. Patients with disease at baseline were considered to have an event on the day of randomization. CT and MRI were mandatory to establish recurrence. Yearly recurrence-free survival rates, eg. at 1 year, defined as the probability that a participant was recurrence-free at 1 year following randomization, were estimated for each treatment group using the Kaplan-Meier product-limit method, along with their corresponding log-log transformed 95% confidence intervals.
Time Frame Randomization up to Years 1, 2, and 3
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients (ITT), analyzed in the arm to which they were allocated by randomization were analyzed.
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description:
Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg by IV infusion, every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Overall Number of Participants Analyzed 475 476
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
RFS Rate at 1 Year
63.50
(58.89 to 67.74)
56.13
(51.52 to 60.47)
RFS Rate at 2 Years
51.45
(46.69 to 56.00)
43.83
(39.27 to 48.28)
RFS Rate at 3 Years
46.48
(41.46 to 51.34)
34.79
(30.12 to 39.50)
4.Secondary Outcome
Title Number of Patients With Distant Metastasis or Death as Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
Hide Description Distant Metastasis-Free Survival (DMFS) was programmatically determined based on the first date of distant metastasis provided by the IRC and was defined as the time between the date of randomization and the date of first distant metastasis or death (whatever the cause), whichever occurred first. A patient who died without reported disease distant metastasis was considered to have distant metastasis on the date of death. For those who remained alive and metastasis-free, DMFS was censored on the date of last evaluable post-randomization tumor assessment. For those who remained alive and had no recorded post-randomization tumor assessment, DMFS was censored on the day of randomization. Patients with disease at baseline were considered to have an event on the day of randomization. Disease was assessed at baseline (randomization) and every 12 weeks (±2 weeks) for 3 years, then every 24 weeks until documented distant progression.
Time Frame From June 2008 to January 2016 (approximately 90 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Population
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description:
Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg, by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Overall Number of Participants Analyzed 475 476
Measure Type: Count of Participants
Unit of Measure: Participants
227
  47.8%
279
  58.6%
5.Secondary Outcome
Title Rate of Overall Survival (OS)
Hide Description OS was defined as the time from the date of randomization to the date of death. For those participants who have not died, OS was censored at the recorded last non-missing date of contact for which the participant was known to be alive.
Time Frame From date of randomization to date of death, assessed up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Population
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description:
Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg, by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Overall Number of Participants Analyzed 475 476
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
OS Rate at 1 year
93.53
(90.88 to 95.43)
87.72
(84.40 to 90.37)
OS Rate at 2 years
82.55
(78.76 to 85.73)
75.27
(71.10 to 78.92)
OS Rate at 3 years
74.20
(69.90 to 77.98)
65.43
(60.91 to 69.56)
OS Rate at 4 years
67.79
(63.24 to 71.90)
60.34
(55.72 to 64.64)
OS Rate at 5 years
65.42
(60.80 to 69.64)
54.43
(49.71 to 58.89)
6.Secondary Outcome
Title Number of Patients With Adverse Events (AEs) Leading to Discontinuation of Treatment, Serious AEs (SAEs), Drug-Related SAEs, Immune-related AEs (irAEs), Immune-mediated Adverse Reactions (imARs), Deaths in Treated Population
Hide Description AEs: Medical Dictionary for Regulatory Activities (MedDRA) version 16.1. irAEs=unknown etiology consistent with an immune phenomenon, considered as causally related to drug. imARs=based on investigator’s assessment of immune-mediated etiology [excluding novel maintenance events (ie, patients with imARs occurring for the first time during maintenance)]. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related (D-R)=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death.
Time Frame Day 1 up to 70 days after last dose or last known alive date for patients still being dosed; up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least one dose of treatment were analyzed. Patients were analyzed in their randomized group provided they received the randomized treatment at least once; those who received incorrect medication for the entire treatment period were analyzed in the group associated with the incorrect medication.
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description:
Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg by IV infusion, every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Overall Number of Participants Analyzed 471 474
Measure Type: Number
Unit of Measure: participants
On-study AE leading to Discontinuation (Any Grade) 245 42
On-study SAE (Any Grade) 254 119
On-study D-R SAE (Any Grade) 216 10
On-study irAE (Any Grade) 426 183
On-study gastrointestinal irAE(Any Grade) 218 84
On-study endocrine irAE(Any Grade) 177 31
On-study liver irAE(Any Grade) 118 21
On-study skin irAE(Any Grade) 298 99
On-study neurological irAE(Any Grade) 21 9
On-study other irAE(Any Grade) 111 21
On-study imAR ( Grade 3-5) 175 9
On-study enterocolitis imAR (Grade 3-5) 67 3
On-study endocrinopathy imAR (Grade 3-5) 38 0
On-study hepatitis imAR (Grade 3-5) 50 1
On-study dermatitis imAR (Grade 3-5) 18 0
On-study neuropathy imAR (Grade 3-5) 5 0
On-study other imAR (Grade 3-5) 27 6
Any Death 122 160
Death within 70 days of last dose study drug 6 6
Death within 30 days of last dose study drug 1 0
Drug-related Deaths 5 0
7.Secondary Outcome
Title Exposure Adjusted Incidence Rate of Adverse Events Including Multiple Occurrences of Unique Events
Hide Description P-Y = person-years of exposure. Incidence rate per 100 person-years of exposure (IR/100 P-Y) was calculated as event count * 100 /person-years of exposure. MedDRA Version: 16.1. Duplicate AEs have been eliminated and overlapping and contiguous occurrences of the same event have been collapsed.
Time Frame Day 1 up to 70 days after last dose or last known alive date for participants still being dosed; up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least one dose of ipilimumab or placebo, adjusted for person-years (P-Y) of exposure; P-Y=440.5; P-Y=728.1 for ipilimumab and placebo, respectively.
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description:
Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg by IV infusion, every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Overall Number of Participants Analyzed 471 474
Measure Type: Number
Unit of Measure: events/100 person-years of exposure
1225.6 482.5
8.Secondary Outcome
Title Mean Change From Baseline in Global Health Status Scores at Each Assessment Timepoint
Hide Description Global health status was measured using European Organization for Research and Treatment of Cancer (EORTC) Quality Life Questionnaire (QLQ) C-30. This health related quality of life (HRQoL) questionnaire was comprised of 15 questions on functional scales, 13 questions on symptom scales and 2 on global health status scale. Global Health Status used a 7 point Likert-type scale of 1 (Very poor) to 7 (Excellent). All scales linearly transformed to 0-100 scales. Higher scores for Global Health Status indicate better HRQoL. An increase from baseline indicates improvement in HRQoL compared to baseline. HRQoL was administered within 1 week prior to first dose (baseline) and on Days 22, 43, 64 (+/- 3 days), Week 24 and every 12 weeks up to 2 years, independent of disease progression.
Time Frame Baseline up to 2 years from randomization
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Hide Analysis Population Description
All randomized patients (ITT) analyzed in the arm to which they were allocated by randomization were analyzed. At timepoint level, all randomized patients (ITT) with a measurement at the timepoint were considered.
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description:
Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg, by IV infusion, every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
Overall Number of Participants Analyzed 400 421
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 4 Day 22 (n=400, 421) -2.29  (15.96) 1.33  (14.02)
Week 7, Day 43 (n=360, 412) -6.64  (20.44) -0.10  (16.75)
Week 10 Day 64 (356, 405) -9.06  (23.56) -0.23  (16.18)
Week 24 Day 162 (300, 347) -4.33  (21.55) 1.37  (17.00)
Week 36 Day 246 (n=290, 307) -5.09  (21.32) 1.52  (18.52)
Week 48 Day 330 (n=275, 276) -3.67  (20.17) 1.54  (18.87)
Week 60 Day 414 (n=242, 255) -5.30  (21.34) 2.84  (17.05)
Week 72 day 498 (n=217, 248) -4.07  (23.19) 1.18  (17.46)
Week 84 Day 582 (n=205, 227) -3.90  (22.06) 1.84  (17.08)
Week 96 Day 666 (n=199, 214) -4.48  (21.71) 1.36  (18.67)
Week 108 Day 750 (n=159,175) -4.35  (20.45) 2.38  (16.81)
Time Frame Day 1 up to 70 days after last dose or last known alive date for patients still being dosed. June 2008 to July 2013.
Adverse Event Reporting Description Study is on-going.
 
Arm/Group Title Ipilimumab 10mg/kg Placebo
Hide Arm/Group Description Ipilimumab (10 mg/kg) as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (every 21 days in the Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, Ipilimumab was administered at a dose of 10 mg/kg by IV infusion, every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed. Placebo as a single dose via a 90 minute intravenous (IV) infusion (not as bolus or IV push) during Days 1, 22, 43 and 64 (Induction Phase) for a total of four separate doses, until disease recurrence, unacceptable toxicity or withdrawal of consent. During the maintenance phase, placebo was administered by IV infusion every 12 weeks, beginning at Week 24, until disease recurrence, unacceptable toxicity or withdrawal of consent, for a maximum of 3 years (Week 156). Treatment started within 7 days from randomization, no later than 13 weeks after surgery and only after the lymphadenectomy was fully healed.
All-Cause Mortality
Ipilimumab 10mg/kg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ipilimumab 10mg/kg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   254/471 (53.93%)   119/474 (25.11%) 
Blood and lymphatic system disorders     
Lymphadenopathy  1  5/471 (1.06%)  3/474 (0.63%) 
Lymphoid tissue hyperplasia  1  1/471 (0.21%)  0/474 (0.00%) 
Thrombocytopenia  1  1/471 (0.21%)  1/474 (0.21%) 
Cardiac disorders     
Atrial flutter  1  0/471 (0.00%)  1/474 (0.21%) 
Atrial tachycardia  1  0/471 (0.00%)  1/474 (0.21%) 
Cardiopulmonary failure  1  1/471 (0.21%)  0/474 (0.00%) 
Coronary artery disease  1  0/471 (0.00%)  1/474 (0.21%) 
Acute coronary syndrome  1  0/471 (0.00%)  1/474 (0.21%) 
Atrial fibrillation  1  3/471 (0.64%)  1/474 (0.21%) 
Bifascicular block  1  0/471 (0.00%)  1/474 (0.21%) 
Tachycardia  1  0/471 (0.00%)  1/474 (0.21%) 
Silent myocardial infarction  1  1/471 (0.21%)  0/474 (0.00%) 
Cardiac failure  1  1/471 (0.21%)  0/474 (0.00%) 
Cardiac arrest  1  1/471 (0.21%)  0/474 (0.00%) 
Ear and labyrinth disorders     
Hypoacusis  1  1/471 (0.21%)  0/474 (0.00%) 
Deafness unilateral  1  1/471 (0.21%)  0/474 (0.00%) 
Endocrine disorders     
Endocrine disorder  1  1/471 (0.21%)  1/474 (0.21%) 
Hyperadrenocorticism  1  0/471 (0.00%)  1/474 (0.21%) 
Hyperthyroidism  1  1/471 (0.21%)  0/474 (0.00%) 
Hypophysitis  1  42/471 (8.92%)  0/474 (0.00%) 
Hypopituitarism  1  9/471 (1.91%)  0/474 (0.00%) 
Adrenal insufficiency  1  6/471 (1.27%)  0/474 (0.00%) 
Hypothyroidism  1  3/471 (0.64%)  0/474 (0.00%) 
Thyroiditis  1  1/471 (0.21%)  0/474 (0.00%) 
Basedow's disease  1  1/471 (0.21%)  0/474 (0.00%) 
Autoimmune thyroiditis  1  1/471 (0.21%)  0/474 (0.00%) 
Eye disorders     
Episcleritis  1  1/471 (0.21%)  0/474 (0.00%) 
Uveitis  1  2/471 (0.42%)  0/474 (0.00%) 
Ulcerative keratitis  1  1/471 (0.21%)  0/474 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  3/471 (0.64%)  1/474 (0.21%) 
Colitis ulcerative  1  2/471 (0.42%)  1/474 (0.21%) 
Haemorrhoids  1  0/471 (0.00%)  1/474 (0.21%) 
Nausea  1  4/471 (0.85%)  1/474 (0.21%) 
Pancreatitis  1  1/471 (0.21%)  0/474 (0.00%) 
Pancreatitis acute  1  1/471 (0.21%)  0/474 (0.00%) 
Abdominal pain lower  1  1/471 (0.21%)  0/474 (0.00%) 
Diverticulum intestinal haemorrhagic  1  1/471 (0.21%)  0/474 (0.00%) 
Gastrointestinal haemorrhage  1  1/471 (0.21%)  0/474 (0.00%) 
Oesophageal haemorrhage  1  1/471 (0.21%)  0/474 (0.00%) 
Anal fissure  1  1/471 (0.21%)  0/474 (0.00%) 
Colitis  1  54/471 (11.46%)  1/474 (0.21%) 
Duodenal ulcer  1  1/471 (0.21%)  0/474 (0.00%) 
Ileitis  1  2/471 (0.42%)  0/474 (0.00%) 
Vomiting  1  8/471 (1.70%)  1/474 (0.21%) 
Abdominal hernia  1  0/471 (0.00%)  1/474 (0.21%) 
Constipation  1  1/471 (0.21%)  0/474 (0.00%) 
Diarrhoea  1  36/471 (7.64%)  5/474 (1.05%) 
Intestinal perforation  1  2/471 (0.42%)  0/474 (0.00%) 
Gastritis  1  2/471 (0.42%)  0/474 (0.00%) 
Rectal haemorrhage  1  1/471 (0.21%)  0/474 (0.00%) 
Dysphagia  1  1/471 (0.21%)  0/474 (0.00%) 
Umbilical hernia  1  1/471 (0.21%)  0/474 (0.00%) 
Inguinal hernia  1  1/471 (0.21%)  2/474 (0.42%) 
Gastric haemorrhage  1  1/471 (0.21%)  0/474 (0.00%) 
General disorders     
Cyst  1  0/471 (0.00%)  1/474 (0.21%) 
Disease progression  1  1/471 (0.21%)  4/474 (0.84%) 
Influenza like illness  1  1/471 (0.21%)  0/474 (0.00%) 
Pyrexia  1  18/471 (3.82%)  1/474 (0.21%) 
Asthenia  1  3/471 (0.64%)  0/474 (0.00%) 
Fatigue  1  5/471 (1.06%)  1/474 (0.21%) 
ADVERSE EVENT  1  0/471 (0.00%)  1/474 (0.21%) 
Disease recurrence  1  0/471 (0.00%)  3/474 (0.63%) 
Multi-organ failure  1  1/471 (0.21%)  0/474 (0.00%) 
Sudden death  1  1/471 (0.21%)  0/474 (0.00%) 
Chest pain  1  3/471 (0.64%)  2/474 (0.42%) 
Hepatobiliary disorders     
Hepatocellular injury  1  2/471 (0.42%)  0/474 (0.00%) 
Hepatotoxicity  1  5/471 (1.06%)  0/474 (0.00%) 
Hepatitis  1  4/471 (0.85%)  0/474 (0.00%) 
Autoimmune hepatitis  1  12/471 (2.55%)  1/474 (0.21%) 
Hyperbilirubinaemia  1  1/471 (0.21%)  0/474 (0.00%) 
Immune system disorders     
Drug hypersensitivity  1  1/471 (0.21%)  0/474 (0.00%) 
Autoimmune disorder  1  1/471 (0.21%)  0/474 (0.00%) 
Anaphylactoid reaction  1  1/471 (0.21%)  0/474 (0.00%) 
Sarcoidosis  1  3/471 (0.64%)  1/474 (0.21%) 
Hypersensitivity  1  3/471 (0.64%)  0/474 (0.00%) 
Infections and infestations     
Bronchitis  1  1/471 (0.21%)  0/474 (0.00%) 
Cellulitis  1  1/471 (0.21%)  4/474 (0.84%) 
Endocarditis  1  1/471 (0.21%)  0/474 (0.00%) 
External ear cellulitis  1  0/471 (0.00%)  1/474 (0.21%) 
H1N1 influenza  1  1/471 (0.21%)  0/474 (0.00%) 
Neuroborreliosis  1  1/471 (0.21%)  0/474 (0.00%) 
Perirectal abscess  1  1/471 (0.21%)  0/474 (0.00%) 
Wound infection  1  0/471 (0.00%)  1/474 (0.21%) 
Cystitis  1  2/471 (0.42%)  0/474 (0.00%) 
Herpes zoster  1  1/471 (0.21%)  0/474 (0.00%) 
Lung infection  1  1/471 (0.21%)  0/474 (0.00%) 
Meningitis bacterial  1  0/471 (0.00%)  1/474 (0.21%) 
Post procedural infection  1  0/471 (0.00%)  1/474 (0.21%) 
Viral infection  1  0/471 (0.00%)  1/474 (0.21%) 
Gastroenteritis viral  1  0/471 (0.00%)  1/474 (0.21%) 
Sepsis  1  2/471 (0.42%)  0/474 (0.00%) 
Septic embolus  1  1/471 (0.21%)  0/474 (0.00%) 
Tooth infection  1  1/471 (0.21%)  0/474 (0.00%) 
Gastroenteritis  1  1/471 (0.21%)  1/474 (0.21%) 
Infection  1  1/471 (0.21%)  1/474 (0.21%) 
Meningitis aseptic  1  2/471 (0.42%)  0/474 (0.00%) 
Ophthalmic herpes simplex  1  1/471 (0.21%)  0/474 (0.00%) 
Urinary tract infection  1  1/471 (0.21%)  0/474 (0.00%) 
Erysipelas  1  2/471 (0.42%)  7/474 (1.48%) 
Localised infection  1  1/471 (0.21%)  0/474 (0.00%) 
Meningitis  1  2/471 (0.42%)  0/474 (0.00%) 
Staphylococcal infection  1  2/471 (0.42%)  0/474 (0.00%) 
Lobar pneumonia  1  1/471 (0.21%)  0/474 (0.00%) 
Otitis externa  1  0/471 (0.00%)  1/474 (0.21%) 
Diarrhoea infectious  1  1/471 (0.21%)  0/474 (0.00%) 
Gastrointestinal infection  1  1/471 (0.21%)  0/474 (0.00%) 
Influenza  1  0/471 (0.00%)  1/474 (0.21%) 
Laryngitis  1  1/471 (0.21%)  0/474 (0.00%) 
Osteomyelitis  1  1/471 (0.21%)  0/474 (0.00%) 
Skin infection  1  1/471 (0.21%)  1/474 (0.21%) 
Appendicitis  1  2/471 (0.42%)  1/474 (0.21%) 
Appendicitis perforated  1  0/471 (0.00%)  3/474 (0.63%) 
Bacteraemia  1  1/471 (0.21%)  0/474 (0.00%) 
Bacterial infection  1  1/471 (0.21%)  1/474 (0.21%) 
Beta haemolytic streptococcal infection  1  1/471 (0.21%)  0/474 (0.00%) 
Groin infection  1  0/471 (0.00%)  1/474 (0.21%) 
Pneumonia  1  3/471 (0.64%)  1/474 (0.21%) 
Injury, poisoning and procedural complications     
Femoral neck fracture  1  0/471 (0.00%)  1/474 (0.21%) 
Post procedural complication  1  1/471 (0.21%)  0/474 (0.00%) 
Seroma  1  0/471 (0.00%)  1/474 (0.21%) 
Procedural complication  1  1/471 (0.21%)  0/474 (0.00%) 
Gastrointestinal stoma complication  1  1/471 (0.21%)  0/474 (0.00%) 
Infusion related reaction  1  1/471 (0.21%)  0/474 (0.00%) 
Radius fracture  1  0/471 (0.00%)  1/474 (0.21%) 
Incisional hernia  1  0/471 (0.00%)  1/474 (0.21%) 
Investigations     
Alanine aminotransferase increased  1  17/471 (3.61%)  0/474 (0.00%) 
Thyroid function test abnormal  1  2/471 (0.42%)  0/474 (0.00%) 
Ejection fraction decreased  1  0/471 (0.00%)  1/474 (0.21%) 
Transaminases increased  1  3/471 (0.64%)  0/474 (0.00%) 
Liver function test abnormal  1  1/471 (0.21%)  0/474 (0.00%) 
Lymph nodes scan abnormal  1  1/471 (0.21%)  1/474 (0.21%) 
Aspartate aminotransferase increased  1  15/471 (3.18%)  0/474 (0.00%) 
Lipase increased  1  1/471 (0.21%)  0/474 (0.00%) 
Weight decreased  1  1/471 (0.21%)  0/474 (0.00%) 
Gamma-glutamyltransferase increased  1  1/471 (0.21%)  0/474 (0.00%) 
Blood corticotrophin decreased  1  0/471 (0.00%)  1/474 (0.21%) 
Blood creatinine increased  1  1/471 (0.21%)  0/474 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  4/471 (0.85%)  0/474 (0.00%) 
Hypoglycaemia  1  1/471 (0.21%)  0/474 (0.00%) 
Hypercalcaemia  1  0/471 (0.00%)  1/474 (0.21%) 
Hyponatraemia  1  2/471 (0.42%)  1/474 (0.21%) 
Hyperglycaemia  1  1/471 (0.21%)  0/474 (0.00%) 
Hypokalaemia  1  1/471 (0.21%)  0/474 (0.00%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  0/471 (0.00%)  1/474 (0.21%) 
Arthralgia  1  2/471 (0.42%)  0/474 (0.00%) 
Neck mass  1  1/471 (0.21%)  0/474 (0.00%) 
Back pain  1  0/471 (0.00%)  1/474 (0.21%) 
Intervertebral disc protrusion  1  1/471 (0.21%)  0/474 (0.00%) 
Arthritis  1  1/471 (0.21%)  2/474 (0.42%) 
Osteoarthritis  1  0/471 (0.00%)  2/474 (0.42%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant melanoma in situ  1  1/471 (0.21%)  3/474 (0.63%) 
Metastases to breast  1  1/471 (0.21%)  0/474 (0.00%) 
Squamous cell carcinoma of skin  1  0/471 (0.00%)  3/474 (0.63%) 
Metastases to adrenals  1  1/471 (0.21%)  0/474 (0.00%) 
Metastases to central nervous system  1  0/471 (0.00%)  2/474 (0.42%) 
Rectal cancer stage 0  1  0/471 (0.00%)  1/474 (0.21%) 
Adrenal adenoma  1  0/471 (0.00%)  1/474 (0.21%) 
Benign salivary gland neoplasm  1  1/471 (0.21%)  0/474 (0.00%) 
Metastases to skin  1  0/471 (0.00%)  1/474 (0.21%) 
Squamous cell carcinoma  1  0/471 (0.00%)  6/474 (1.27%) 
Adenocarcinoma  1  0/471 (0.00%)  1/474 (0.21%) 
Liposarcoma  1  1/471 (0.21%)  0/474 (0.00%) 
Malignant neoplasm progression  1  0/471 (0.00%)  1/474 (0.21%) 
Malignant pleural effusion  1  0/471 (0.00%)  1/474 (0.21%) 
Melanocytic naevus  1  0/471 (0.00%)  1/474 (0.21%) 
Metastases to bone  1  0/471 (0.00%)  1/474 (0.21%) 
Metastases to lung  1  2/471 (0.42%)  0/474 (0.00%) 
Metastatic malignant melanoma  1  2/471 (0.42%)  10/474 (2.11%) 
Neoplasm progression  1  0/471 (0.00%)  2/474 (0.42%) 
Parathyroid tumour benign  1  0/471 (0.00%)  1/474 (0.21%) 
Melanoma recurrent  1  1/471 (0.21%)  7/474 (1.48%) 
Metastases to lymph nodes  1  1/471 (0.21%)  2/474 (0.42%) 
Metastasis  1  0/471 (0.00%)  1/474 (0.21%) 
Benign lung neoplasm  1  1/471 (0.21%)  0/474 (0.00%) 
Endobronchial lipoma  1  1/471 (0.21%)  0/474 (0.00%) 
Basal cell carcinoma  1  2/471 (0.42%)  9/474 (1.90%) 
Metastases to meninges  1  0/471 (0.00%)  1/474 (0.21%) 
Malignant melanoma  1  4/471 (0.85%)  11/474 (2.32%) 
Prostate cancer  1  0/471 (0.00%)  1/474 (0.21%) 
Nervous system disorders     
Presyncope  1  1/471 (0.21%)  0/474 (0.00%) 
Cranial nerve disorder  1  1/471 (0.21%)  1/474 (0.21%) 
Guillain-Barre syndrome  1  1/471 (0.21%)  0/474 (0.00%) 
Haemorrhage intracranial  1  1/471 (0.21%)  0/474 (0.00%) 
Meningoradiculitis  1  1/471 (0.21%)  0/474 (0.00%) 
Syncope  1  2/471 (0.42%)  0/474 (0.00%) 
Ataxia  1  0/471 (0.00%)  1/474 (0.21%) 
Cerebral thrombosis  1  0/471 (0.00%)  1/474 (0.21%) 
Trigeminal nerve disorder  1  1/471 (0.21%)  0/474 (0.00%) 
Convulsion  1  0/471 (0.00%)  2/474 (0.42%) 
Peripheral motor neuropathy  1  1/471 (0.21%)  0/474 (0.00%) 
Axonal neuropathy  1  1/471 (0.21%)  0/474 (0.00%) 
Neuropathy peripheral  1  1/471 (0.21%)  0/474 (0.00%) 
Polyneuropathy  1  1/471 (0.21%)  0/474 (0.00%) 
Spinal cord compression  1  0/471 (0.00%)  1/474 (0.21%) 
Autoimmune neuropathy  1  1/471 (0.21%)  0/474 (0.00%) 
Peripheral sensory neuropathy  1  1/471 (0.21%)  0/474 (0.00%) 
Carotid artery stenosis  1  0/471 (0.00%)  1/474 (0.21%) 
Headache  1  6/471 (1.27%)  2/474 (0.42%) 
Psychiatric disorders     
Depression  1  2/471 (0.42%)  0/474 (0.00%) 
Mental status changes  1  1/471 (0.21%)  1/474 (0.21%) 
Confusional state  1  1/471 (0.21%)  0/474 (0.00%) 
Substance-induced psychotic disorder  1  1/471 (0.21%)  0/474 (0.00%) 
Renal and urinary disorders     
Cystitis haemorrhagic  1  1/471 (0.21%)  0/474 (0.00%) 
Renal failure  1  2/471 (0.42%)  0/474 (0.00%) 
Urinary tract obstruction  1  1/471 (0.21%)  0/474 (0.00%) 
Cystitis noninfective  1  1/471 (0.21%)  0/474 (0.00%) 
Hydronephrosis  1  0/471 (0.00%)  1/474 (0.21%) 
Reproductive system and breast disorders     
Endometrial hyperplasia  1  0/471 (0.00%)  1/474 (0.21%) 
Ovarian cyst  1  0/471 (0.00%)  1/474 (0.21%) 
Respiratory, thoracic and mediastinal disorders     
Interstitial lung disease  1  1/471 (0.21%)  0/474 (0.00%) 
Pulmonary embolism  1  1/471 (0.21%)  2/474 (0.42%) 
Lung infiltration  1  1/471 (0.21%)  0/474 (0.00%) 
Pulmonary sarcoidosis  1  2/471 (0.42%)  0/474 (0.00%) 
Pneumonitis  1  3/471 (0.64%)  0/474 (0.00%) 
Hypoxia  1  1/471 (0.21%)  0/474 (0.00%) 
Pneumothorax  1  0/471 (0.00%)  1/474 (0.21%) 
Eosinophilic pneumonia  1  1/471 (0.21%)  0/474 (0.00%) 
Oropharyngeal pain  1  1/471 (0.21%)  0/474 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/471 (0.21%)  0/474 (0.00%) 
Pruritus  1  1/471 (0.21%)  0/474 (0.00%) 
Angioedema  1  1/471 (0.21%)  0/474 (0.00%) 
Skin exfoliation  1  0/471 (0.00%)  1/474 (0.21%) 
Drug eruption  1  1/471 (0.21%)  0/474 (0.00%) 
Exfoliative rash  1  0/471 (0.00%)  1/474 (0.21%) 
Actinic keratosis  1  0/471 (0.00%)  1/474 (0.21%) 
Rash maculo-papular  1  1/471 (0.21%)  0/474 (0.00%) 
Vascular disorders     
Lymphoedema  1  1/471 (0.21%)  1/474 (0.21%) 
Hypotension  1  4/471 (0.85%)  0/474 (0.00%) 
Haematoma  1  0/471 (0.00%)  2/474 (0.42%) 
Circulatory collapse  1  0/471 (0.00%)  1/474 (0.21%) 
Withdrawal hypertension  1  0/471 (0.00%)  1/474 (0.21%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ipilimumab 10mg/kg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   440/471 (93.42%)   380/474 (80.17%) 
Endocrine disorders     
Hypophysitis  1  62/471 (13.16%)  3/474 (0.63%) 
Hypothyroidism  1  45/471 (9.55%)  6/474 (1.27%) 
Gastrointestinal disorders     
Abdominal pain  1  64/471 (13.59%)  44/474 (9.28%) 
Nausea  1  116/471 (24.63%)  82/474 (17.30%) 
Colitis  1  43/471 (9.13%)  5/474 (1.05%) 
Vomiting  1  59/471 (12.53%)  27/474 (5.70%) 
Constipation  1  30/471 (6.37%)  29/474 (6.12%) 
Diarrhoea  1  228/471 (48.41%)  141/474 (29.75%) 
General disorders     
Influenza like illness  1  35/471 (7.43%)  30/474 (6.33%) 
Oedema peripheral  1  21/471 (4.46%)  26/474 (5.49%) 
Pyrexia  1  73/471 (15.50%)  21/474 (4.43%) 
Asthenia  1  29/471 (6.16%)  37/474 (7.81%) 
Fatigue  1  188/471 (39.92%)  143/474 (30.17%) 
Infections and infestations     
Nasopharyngitis  1  20/471 (4.25%)  29/474 (6.12%) 
Investigations     
Alanine aminotransferase increased  1  95/471 (20.17%)  26/474 (5.49%) 
Blood lactate dehydrogenase increased  1  32/471 (6.79%)  12/474 (2.53%) 
Blood testosterone decreased  1  28/471 (5.94%)  8/474 (1.69%) 
Aspartate aminotransferase increased  1  71/471 (15.07%)  24/474 (5.06%) 
Lipase increased  1  43/471 (9.13%)  30/474 (6.33%) 
Weight decreased  1  147/471 (31.21%)  36/474 (7.59%) 
Weight increased  1  69/471 (14.65%)  110/474 (23.21%) 
Metabolism and nutrition disorders     
Decreased appetite  1  65/471 (13.80%)  16/474 (3.38%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal pain  1  16/471 (3.40%)  24/474 (5.06%) 
Pain in extremity  1  21/471 (4.46%)  35/474 (7.38%) 
Arthralgia  1  33/471 (7.01%)  43/474 (9.07%) 
Back pain  1  29/471 (6.16%)  40/474 (8.44%) 
Nervous system disorders     
Dizziness  1  29/471 (6.16%)  18/474 (3.80%) 
Headache  1  150/471 (31.85%)  85/474 (17.93%) 
Psychiatric disorders     
Anxiety  1  21/471 (4.46%)  24/474 (5.06%) 
Insomnia  1  45/471 (9.55%)  21/474 (4.43%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  30/471 (6.37%)  15/474 (3.16%) 
Cough  1  68/471 (14.44%)  48/474 (10.13%) 
Skin and subcutaneous tissue disorders     
Rash  1  185/471 (39.28%)  80/474 (16.88%) 
Pruritus  1  202/471 (42.89%)  70/474 (14.77%) 
Dermatitis acneiform  1  26/471 (5.52%)  5/474 (1.05%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
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):
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00636168     History of Changes
Other Study ID Numbers: CA184-029
EORTC 18071
First Submitted: March 7, 2008
First Posted: March 14, 2008
Results First Submitted: July 25, 2014
Results First Posted: August 19, 2014
Last Update Posted: November 6, 2017