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Trial record 40 of 115 for:    cancer | butyrate

Evaluation of Tumor Response to Ipilimumab in the Treatment of Melanoma With Brain Metastases

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ClinicalTrials.gov Identifier: NCT00623766
Recruitment Status : Completed
First Posted : February 26, 2008
Results First Posted : June 9, 2014
Last Update Posted : June 9, 2014
Sponsor:
Collaborator:
Medarex
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Interventions Drug: Ipilimumab
Drug: Corticosteroid: Betamethasone
Drug: Corticosteroid: Dexamethasone
Drug: Corticosteroid: Fludrocortisone
Drug: Corticosteroid: Hydrocortisone
Drug: Corticosteroid: Meprednisone
Drug: Corticosteroid: Methylprednisolone
Drug: Corticosteroid: Prednisolone
Drug: Corticosteroid: Prednisone
Drug: Corticosteroid: Triamcinolone
Enrollment 99
Recruitment Details  
Pre-assignment Details A total of 99 participants were enrolled, and 27 did not receive treatment because they did not meet screening criteria.
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Period Title: Induction Phase (Day 1 to Week 24)
Started 51 [1] 21 [1]
Completed 15 [2] 5 [3]
Not Completed 36 16
Reason Not Completed
Off treatment             36             16
[1]
Participants who received treatment
[2]
4 patients completed Induction but did not enter Maintenance; they were only followed up with scans.
[3]
3 patients completed Induction but did not enter Maintenance; they were only followed up with scans.
Period Title: Maintenance Phase (Week 24 to Year 2)
Started 11 2
Completed 1 [1] 0
Not Completed 10 2
Reason Not Completed
Disease progression             4             0
Administrative reason by sponsor             4             0
Withdrawal by Subject             1             2
Patient required surgery             1             0
[1]
Inadvertently not noted as discontinued (disease progression); data collection error at site closure
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients Total
Hide Arm/Group Description Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. Participants who were dependent on corticosteroid therapy received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. Total of all reporting groups
Overall Number of Baseline Participants 51 21 72
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 51 participants 21 participants 72 participants
Younger than 65 years 39 17 56
65 years and older 12 4 16
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 21 participants 72 participants
Female
18
  35.3%
10
  47.6%
28
  38.9%
Male
33
  64.7%
11
  52.4%
44
  61.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 21 participants 72 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
51
 100.0%
21
 100.0%
72
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Eastern Cooperative Oncology Group (ECOG) score   [1] 
Measure Type: Number
Unit of measure:  Units on a scale
Number Analyzed 51 participants 21 participants 72 participants
0 25 14 39
1 26 7 33
[1]
Measure Description: ECOG performance status assesses a participant's physical ability on a 6-point scale: 0=fully active, able to carry on all predisease activities without restriction; 1=restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Score of 0=best status and 5=worst status.
1.Primary Outcome
Title Disease Control Rate by Modified World Health Organization (mWHO) Tumor Assessment Criteria
Hide Description Disease control rate is defined as the number of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) (global, in brain, or outside of brain) based on mWHO criteria divided by the number of patients who received treatment. By mWHO criteria: CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the 2 largest perpendicular diameters of all index lesions. SD=does not meet criteria for CR or PR, in the absence of progressive disease (PD). Patients with PR or CR not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions. PD=at least 25% increase in the sum of the diameters of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesions. CNS=central nervous system.
Time Frame From Day 1, first dose to end of Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description:
Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Global disease control rate
17.6
(8.4 to 30.9)
4.8
(0.1 to 23.8)
Disease control rate in brain
23.5
(12.8 to 37.5)
9.5
(1.2 to 30.4)
2.Secondary Outcome
Title Disease Control Rate by Immune-related Response Criteria (irRC)
Hide Description Disease control rate is defined as the number of patients with a best overall response of immune-related (ir) complete response (irCR), partial response (irPR), or stable disease (irSD) divided by the total number of patients who received treatment. By irRC definition: irCR=complete disappearance of all index lesions. irPR=decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index lesions. irSD=does not meet criteria for irCR or irPR, in the absence of ir progressive disease (irPD). irPD=at least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline). CNS=central nervous system; non-CNS compartment=extracranial, or outside of the brain.
Time Frame From Day 1, first dose to end of Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab
Arm/Group Title Ipilimumab 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description:
Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Global disease control rate
25.5
(14.3 to 39.6)
9.5
(1.2 to 30.4)
Disease control rate in brain lesions
25.5
(14.3 to 39.6)
9.5
(1.2 to 30.4)
Disease control rate in non-CNS compartment
33.3
(20.8 to 47.9)
9.5
(1.2 to 30.4)
3.Secondary Outcome
Title Best Overall Response Rate (BORR) by Modified World Health Organization (mWHO) Criteria and by Immune-relate Response Criteria (irRC)
Hide Description BORR is defined as the number of patients whose global best overall response (BOR) was complete (CR) or partial response (PR), divided by the total number of participants who received treatment. CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index lesions. The global BOR is the best overall response (OR) designation over the study as a whole for an individual in the study based on overall tumor burden. Both central nervous system (CNS) (brain lesions) and non-CNS compartments (lesions outside the brain) are considered for the global BOR. For the analysis of global BOR of CR or PR (by both modified WHO criteria and immune-related response criteria [irRC]), the OR assessment must be confirmed by a second (confirmatory) evaluation meeting the criteria for response and must be performed no less than 4 weeks after the criteria for response are first met.
Time Frame From Day 1, first dose until the last tumor assessment, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description:
Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Global BORR (mWHO criteria)
9.8
(3.3 to 21.4)
4.8
(0.1 to 23.8)
BORR in brain (mWHO criteria)
15.7
(7.0 to 28.6)
4.8
(0.1 to 23.8)
BORR in non-CNS compartment (mWHO criteria)
13.7
(5.7 to 26.3)
4.8
(0.1 to 23.8)
Global BORR (irRC)
9.8
(3.3 to 21.4)
4.8
(0.1 to 23.8)
BORR in brain (irRC)
15.7
(7.0 to 28.6)
4.8
(0.1 to 23.8)
BORR in non-CNS compartment (irRC criteria )
13.7
(5.7 to 26.3)
4.8
(0.1 to 23.8)
4.Secondary Outcome
Title Duration of Response (DOR) by Modified World Health Organization (mWHO) Criteria and by Immune-related Response Criteria (irRC)
Hide Description DOR is defined in patients whose global best overall response is complete (CR) or partial response (PR) as the time between the date of response of confirmed CR or PR, whichever occurs first, and the date of progressive disease or death, whichever occurs first. For patients who remain alive and have not progressed following response, duration of response will be censored on the date of last evaluable tumor assessment.
Time Frame From Day 1, first dose to last tumor assessment up to 18.2 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description:
Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Participants who were dependent on corticosteroid therapy received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Median (95% Confidence Interval)
Unit of Measure: Months
DOR by mWHO criteria
10.4
(2.9 to 18.2)
NA [1] 
(NA to NA)
DOR by irRC
10.4
(2.9 to 18.2)
NA [1] 
(NA to NA)
[1]
The only corticosteroid-dependent patient with response has not progressed or died
5.Secondary Outcome
Title Progression-free Survival (PFS) by Modified World Health Organization (mWHO) Criteria and by Immune-related Response Criteria (irRC)
Hide Description PFS is defined as the time between the date of the first dose of study therapy and the date of progression or death, whichever occurs first. A patient who dies without reported prior progression will be considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS will be censored on the date of last evaluable tumor assessment. Participants who have not died and have no recorded postbaseline tumor assessment will be censored on the date of first dose of study therapy. Those who die without any recorded postbaseline tumor assessment will be considered to have progressed on the date of death.
Time Frame From Day 1, first dose to the date of progression or death, whichever occurred first up to 22 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description:
Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Median (95% Confidence Interval)
Unit of Measure: Months
Global PFS (mWHO criteria)
1.4
(1.2 to 2.6)
1.2
(1.2 to 1.3)
PFS in brain (mWHO criteria)
1.5
(1.2 to 2.6)
1.2
(1.2 to 1.3)
PFS in non-CNS compartment (mWHO criteria)
2.6
(1.3 to 4.1)
1.3
(1.2 to 2.5)
Global PFS (irRC)
2.7
(1.6 to 3.7)
1.3
(1.2 to 2.5)
PFS in brain (irRC)
1.9
(1.2 to 2.9)
1.2
(1.2 to 1.3)
PFS in non-CNS compartment (irRC)
3.3
(2.6 to 4.7)
1.3
(1.2 to 2.5)
6.Secondary Outcome
Title Number of Participants Surviving at 6, 12, 18, 24, and 36 Months (Overall Survival [OS] Rate)
Hide Description OS is defined as the time from the first dose of study drug until the date of death. Overall survival rate is the percentage of participants known to be alive at a timepoint. For those patients who did not die, OS was censored at the recorded last date of patient contact, and those with a missing recorded last date of contact will be censored at the last date the patient was known to be alive. The survival rate at a specified time-point is the probability that a patient is alive at that time following randomization. The rate is calculated for each treatment group using the Kaplan-Meier product-limit method. A corresponding 2-sided 95% bootstrap confidence interval will be calculated.
Time Frame From first dose to Months 6, 12, 18, 24, and 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description:
Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability of being alive
At 6 months
0.55
(0.41 to 0.68)
0.38
(0.17 to 0.59)
At 12 months
0.31
(0.18 to 0.44)
0.19
(0.02 to 0.36)
At 18 months
0.26
(0.14 to 0.39)
0.19
(0.02 to 0.36)
At 24 months
0.26
(0.14 to 0.39)
0.10
(0.00 to 0.22)
At 36 months
0.26
(0.14 to 0.39)
0.10
(0.00 to 0.22)
7.Secondary Outcome
Title Number of Participants Who Died or Had a Treatment-related Adverse Event (AE), Immune-related AE, Immune-related Serious Adverse Event (SAE), Nervous System Disorder, Treatment-related Nervous System Disorder, SAE, and AE Leading to Discontinuation
Hide Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame Continuously from Day 1, first dose, to 70 days following last dose of ipilimumab
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description:
Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Participants who were dependent on corticosteroid therapy received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Measure Type: Number
Unit of Measure: Participants
Deaths 37 20
Treatment-related AEs (all) 45 17
Treatment-related AEs (Grade 3/4) 17 4
Treatment-related AEs (Fatal) 0 0
Immune-related AEs (All) 35 13
Immune-related AEs (Grade 3/4) 11 3
Immune-related AEs (Fatal) 0 0
Immune-related SAEs (All) 11 6
Immune-related SAES (Grade 3/4) 7 3
Immune-related SAES (Fatal) 0 0
Nervous system disorder (NSD) (All) 40 14
NSD (Grade 3/4) 17 7
NSD (Fatal) 0 1
Treatment-related NSD (All) 8 3
Treatment-related NSD (Gr 3/4) 1 0
Treatment-related NSD (Fatal) 0 0
SAE (All) 36 17
SAE (Grade 3/4) 18 7
SAE (Fatal) 17 10
AEs leading to discontinuation (All) 15 9
AEs leading to discontinuation (Grade 3/4) 9 4
AEs leading to discontinuation (Fatal) 5 4
8.Secondary Outcome
Title Onset of Response by Modified World Health Organization (mWHO) Criteria and Immune-related Response Criteria (irRC)
Hide Description Onset of response is defined as the time between the first dose of study therapy and the date when measurement criteria are first met for global best overall response of partial (PR) or complete (CR), whichever occurs first. CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the 2 largest perpendicular diameters of all index lesions.
Time Frame From Day 1, first dose to a maximum of 4.2 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab. n=number of participants with a best overall response of CR or PR.
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients
Hide Arm/Group Description:
Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Participants who were dependent on corticosteroid therapy received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Median (Full Range)
Unit of Measure: Months
Onset of response (mWHO criteria) (n=5, 1)
1.2
(1.1 to 4.2)
1.2
(1.2 to 1.2)
Onset of response (irRC) (n=5, 1)
1.2
(1.1 to 4.2)
1.2
(1.2 to 1.2)
9.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time from date of first dose of study drug until the date of death. For those patients who did not die, OS was censored at the recorded last date of patient contact, and those missing a recorded last date of contact will be censored at the last date the patient was known to be alive.
Time Frame From first dose to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of ipilimumab
Arm/Group Title Ipilimumab, 10 mg/kg, IV in Corticosteroid-free Patients Ipilimumab, 10 mg/kg, IV in Corticosteroid-dependent Patients
Hide Arm/Group Description:

Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV, every 12 weeks, beginning at Week 24.

Ipilimumab: 10 mg/kg, administered as an intravenous infusion every 3 weeks during induction and every 12 weeks during maintenance

Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
Overall Number of Participants Analyzed 51 21
Median (95% Confidence Interval)
Unit of Measure: Months
6.97
(4.14 to 10.81)
3.75
(1.64 to 7.33)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients
Hide Arm/Group Description Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24.
All-Cause Mortality
Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients
Affected / at Risk (%) Affected / at Risk (%)
Total   17/21 (80.95%)   36/51 (70.59%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  0/21 (0.00%)  1/51 (1.96%) 
Cardiac disorders     
Bradycardia  1  0/21 (0.00%)  1/51 (1.96%) 
Atrial fibrillation  1  0/21 (0.00%)  1/51 (1.96%) 
Endocrine disorders     
Adrenal insufficiency  1  1/21 (4.76%)  2/51 (3.92%) 
Hypophysitis  1  0/21 (0.00%)  1/51 (1.96%) 
Eye disorders     
Conjunctivitis  1  0/21 (0.00%)  2/51 (3.92%) 
Retinal detachment  1  0/21 (0.00%)  1/51 (1.96%) 
Gastrointestinal disorders     
Intestinal ischaemia  1  0/21 (0.00%)  1/51 (1.96%) 
Ascites  1  0/21 (0.00%)  1/51 (1.96%) 
Diarrhoea  1  2/21 (9.52%)  6/51 (11.76%) 
Pancreatitis  1  0/21 (0.00%)  1/51 (1.96%) 
Abdominal pain  1  0/21 (0.00%)  2/51 (3.92%) 
Haematochezia  1  1/21 (4.76%)  0/51 (0.00%) 
Small intestinal obstruction  1  0/21 (0.00%)  1/51 (1.96%) 
Vomiting  1  0/21 (0.00%)  5/51 (9.80%) 
Colitis  1  3/21 (14.29%)  5/51 (9.80%) 
Nausea  1  0/21 (0.00%)  5/51 (9.80%) 
Peritoneal haemorrhage  1  1/21 (4.76%)  0/51 (0.00%) 
General disorders     
Fatigue  1  1/21 (4.76%)  2/51 (3.92%) 
Pyrexia  1  0/21 (0.00%)  3/51 (5.88%) 
Disease progression  1  10/21 (47.62%)  16/51 (31.37%) 
Pain  1  0/21 (0.00%)  1/51 (1.96%) 
Hepatobiliary disorders     
Bile duct stone  1  0/21 (0.00%)  1/51 (1.96%) 
Hyperbilirubinaemia  1  0/21 (0.00%)  1/51 (1.96%) 
Immune system disorders     
Hypersensitivity  1  1/21 (4.76%)  0/51 (0.00%) 
Infections and infestations     
Pneumonia  1  0/21 (0.00%)  3/51 (5.88%) 
Pneumonia viral  1  0/21 (0.00%)  1/51 (1.96%) 
Sepsis  1  1/21 (4.76%)  1/51 (1.96%) 
Metapneumovirus infection  1  0/21 (0.00%)  1/51 (1.96%) 
Colon gangrene  1  0/21 (0.00%)  1/51 (1.96%) 
Septic shock  1  0/21 (0.00%)  1/51 (1.96%) 
Bacteraemia  1  1/21 (4.76%)  0/51 (0.00%) 
Urinary tract infection  1  0/21 (0.00%)  1/51 (1.96%) 
Injury, poisoning and procedural complications     
Fracture  1  1/21 (4.76%)  0/51 (0.00%) 
Brain herniation  1  0/21 (0.00%)  1/51 (1.96%) 
Investigations     
Lipase increased  1  0/21 (0.00%)  1/51 (1.96%) 
Aspartate aminotransferase increased  1  1/21 (4.76%)  0/51 (0.00%) 
Alanine aminotransferase increased  1  1/21 (4.76%)  1/51 (1.96%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  1/21 (4.76%)  0/51 (0.00%) 
Decreased appetite  1  0/21 (0.00%)  1/51 (1.96%) 
Dehydration  1  2/21 (9.52%)  5/51 (9.80%) 
Hyperglycaemia  1  0/21 (0.00%)  1/51 (1.96%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/21 (4.76%)  0/51 (0.00%) 
Muscular weakness  1  1/21 (4.76%)  1/51 (1.96%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain  1  0/21 (0.00%)  1/51 (1.96%) 
Metastatic malignant melanoma  1  0/21 (0.00%)  1/51 (1.96%) 
Nervous system disorders     
Ataxia  1  1/21 (4.76%)  0/51 (0.00%) 
Cerebral haemorrhage  1  1/21 (4.76%)  3/51 (5.88%) 
Syncope  1  1/21 (4.76%)  0/51 (0.00%) 
Cerebrovascular accident  1  0/21 (0.00%)  1/51 (1.96%) 
Hemiparesis  1  2/21 (9.52%)  0/51 (0.00%) 
Mental impairment  1  1/21 (4.76%)  0/51 (0.00%) 
Somnolence  1  0/21 (0.00%)  3/51 (5.88%) 
Lethargy  1  0/21 (0.00%)  1/51 (1.96%) 
Loss of consciousness  1  0/21 (0.00%)  1/51 (1.96%) 
Headache  1  0/21 (0.00%)  2/51 (3.92%) 
Aphasia  1  1/21 (4.76%)  0/51 (0.00%) 
Peripheral sensory neuropathy  1  0/21 (0.00%)  1/51 (1.96%) 
Depressed level of consciousness  1  2/21 (9.52%)  2/51 (3.92%) 
Speech disorder  1  0/21 (0.00%)  1/51 (1.96%) 
Haemorrhage intracranial  1  1/21 (4.76%)  0/51 (0.00%) 
Convulsion  1  3/21 (14.29%)  3/51 (5.88%) 
Peripheral motor neuropathy  1  1/21 (4.76%)  0/51 (0.00%) 
Psychiatric disorders     
Confusional state  1  2/21 (9.52%)  5/51 (9.80%) 
Mental status changes  1  0/21 (0.00%)  2/51 (3.92%) 
Renal and urinary disorders     
Renal failure acute  1  0/21 (0.00%)  1/51 (1.96%) 
Renal failure  1  1/21 (4.76%)  0/51 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Lung infiltration  1  0/21 (0.00%)  1/51 (1.96%) 
Pulmonary embolism  1  0/21 (0.00%)  2/51 (3.92%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/21 (4.76%)  0/51 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  0/21 (0.00%)  1/51 (1.96%) 
Hypotension  1  1/21 (4.76%)  0/51 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients
Affected / at Risk (%) Affected / at Risk (%)
Total   20/21 (95.24%)   48/51 (94.12%) 
Cardiac disorders     
Sinus tachycardia  1  2/21 (9.52%)  0/51 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  2/21 (9.52%)  1/51 (1.96%) 
Eye disorders     
Visual impairment  1  2/21 (9.52%)  1/51 (1.96%) 
Vision blurred  1  2/21 (9.52%)  7/51 (13.73%) 
Gastrointestinal disorders     
Stomatitis  1  2/21 (9.52%)  0/51 (0.00%) 
Dyspepsia  1  2/21 (9.52%)  6/51 (11.76%) 
Constipation  1  5/21 (23.81%)  9/51 (17.65%) 
Diarrhoea  1  9/21 (42.86%)  24/51 (47.06%) 
Abdominal pain  1  3/21 (14.29%)  4/51 (7.84%) 
Vomiting  1  1/21 (4.76%)  10/51 (19.61%) 
Flatulence  1  2/21 (9.52%)  4/51 (7.84%) 
Nausea  1  4/21 (19.05%)  19/51 (37.25%) 
General disorders     
Fatigue  1  11/21 (52.38%)  27/51 (52.94%) 
Pyrexia  1  2/21 (9.52%)  4/51 (7.84%) 
Influenza like illness  1  0/21 (0.00%)  5/51 (9.80%) 
Thirst  1  2/21 (9.52%)  0/51 (0.00%) 
Oedema peripheral  1  6/21 (28.57%)  4/51 (7.84%) 
Gait disturbance  1  3/21 (14.29%)  1/51 (1.96%) 
Chills  1  0/21 (0.00%)  5/51 (9.80%) 
Infections and infestations     
Herpes zoster  1  0/21 (0.00%)  3/51 (5.88%) 
Bronchitis  1  0/21 (0.00%)  3/51 (5.88%) 
Sinusitis  1  0/21 (0.00%)  6/51 (11.76%) 
Injury, poisoning and procedural complications     
Contusion  1  3/21 (14.29%)  2/51 (3.92%) 
Investigations     
Haemoglobin decreased  1  2/21 (9.52%)  2/51 (3.92%) 
Weight decreased  1  1/21 (4.76%)  7/51 (13.73%) 
Aspartate aminotransferase increased  1  3/21 (14.29%)  4/51 (7.84%) 
Blood alkaline phosphatase increased  1  2/21 (9.52%)  4/51 (7.84%) 
Alanine aminotransferase increased  1  3/21 (14.29%)  5/51 (9.80%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  1/21 (4.76%)  3/51 (5.88%) 
Hyponatraemia  1  3/21 (14.29%)  1/51 (1.96%) 
Decreased appetite  1  5/21 (23.81%)  14/51 (27.45%) 
Dehydration  1  2/21 (9.52%)  1/51 (1.96%) 
Hypophosphataemia  1  1/21 (4.76%)  3/51 (5.88%) 
Hyperglycaemia  1  4/21 (19.05%)  4/51 (7.84%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  1/21 (4.76%)  3/51 (5.88%) 
Arthralgia  1  2/21 (9.52%)  3/51 (5.88%) 
Neck pain  1  0/21 (0.00%)  4/51 (7.84%) 
Pain in extremity  1  3/21 (14.29%)  5/51 (9.80%) 
Back pain  1  4/21 (19.05%)  8/51 (15.69%) 
Muscular weakness  1  3/21 (14.29%)  4/51 (7.84%) 
Musculoskeletal stiffness  1  2/21 (9.52%)  3/51 (5.88%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain  1  2/21 (9.52%)  0/51 (0.00%) 
Nervous system disorders     
Dizziness  1  2/21 (9.52%)  11/51 (21.57%) 
Dysgeusia  1  0/21 (0.00%)  4/51 (7.84%) 
Paraesthesia  1  3/21 (14.29%)  1/51 (1.96%) 
Brain oedema  1  0/21 (0.00%)  4/51 (7.84%) 
Headache  1  6/21 (28.57%)  20/51 (39.22%) 
Memory impairment  1  0/21 (0.00%)  5/51 (9.80%) 
Aphasia  1  1/21 (4.76%)  3/51 (5.88%) 
Convulsion  1  1/21 (4.76%)  5/51 (9.80%) 
Hypoaesthesia  1  1/21 (4.76%)  4/51 (7.84%) 
Psychiatric disorders     
Insomnia  1  4/21 (19.05%)  8/51 (15.69%) 
Agitation  1  1/21 (4.76%)  3/51 (5.88%) 
Confusional state  1  1/21 (4.76%)  4/51 (7.84%) 
Renal and urinary disorders     
Polyuria  1  2/21 (9.52%)  0/51 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  2/21 (9.52%)  11/51 (21.57%) 
Dyspnoea  1  2/21 (9.52%)  5/51 (9.80%) 
Skin and subcutaneous tissue disorders     
Rash  1  7/21 (33.33%)  20/51 (39.22%) 
Dry skin  1  0/21 (0.00%)  3/51 (5.88%) 
Hyperhidrosis  1  1/21 (4.76%)  3/51 (5.88%) 
Erythema  1  0/21 (0.00%)  3/51 (5.88%) 
Pruritus  1  6/21 (28.57%)  17/51 (33.33%) 
Vascular disorders     
Hypertension  1  0/21 (0.00%)  4/51 (7.84%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00623766     History of Changes
Other Study ID Numbers: CA184-042
First Submitted: February 19, 2008
First Posted: February 26, 2008
Results First Submitted: December 17, 2013
Results First Posted: June 9, 2014
Last Update Posted: June 9, 2014