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Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma

This study has been completed.
Sponsor:
Collaborator:
Medarex
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00324155
First received: May 8, 2006
Last updated: October 24, 2014
Last verified: October 2014
Results First Received: January 22, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Melanoma
Interventions: Drug: Ipilimumab
Drug: Placebo
Drug: Dacarbazine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was initiated on August 8, 2006. Primary endpoint (Survival) was evaluated on February 7, 2011 and again at completion of follow-up period, October 13, 2013. Participants with a histologic diagnosis of untreated, measurable, and unresectable Stage III or Stage IV malignant melanoma were eligible.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 681 patients enrolled, 502 were randomized, and 498 received treatment. Reasons for not starting treatment: 147 no longer met study criteria (including 3 who were randomized but did not receive treatment), 25 withdrew consent, 3 died, 2 had adverse events, 2 lost to follow-up, 2 poor compliance or noncompliance, 1 not reported, and 1 other.

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks was continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase. Participants who experienced PD or who did not wish to continue study assessments in the Induction or Maintenance Phases entered the Follow-up Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until disease progression (PD), unacceptable toxicity, or withdrawal of consent

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent. Participants who experienced PD or who did not wish to continue study assessments in the Induction or Maintenance Phases entered the Follow-up Phase.


Participant Flow for 4 periods

Period 1:   Enrolled and Randomized
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
STARTED     250     252  
COMPLETED     247 [1]   251 [2]
NOT COMPLETED     3     1  
No longer met study criteria                 3                 0  
Lost to Follow-up                 0                 1  
[1] 3 randomized but who did not receive treatment (no longer met study criteria).
[2] 1 randomized but who did not receive treatment (lost to follow-up).

Period 2:   Received Treatment in Induction Phase
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
STARTED     247     251  
COMPLETED     45 [1]   54 [2]
NOT COMPLETED     202     197  
Disease Progression                 88                 152  
Study Drug Toxicity                 83                 10  
Death                 8                 15  
Deterioration/Undocumented Progression                 9                 8  
Adverse Event                 6                 7  
Withdrawal by Subject                 6                 5  
Physician Decision                 2                 0  
[1] 45 participants on treatment at end of Induction Phase. Study undergoing closure.
[2] 54 participants on treatment at end of Induction Phase. Study undergoing closure.

Period 3:   Received Treatment in Maintenance Phase
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
STARTED     43 [1]   53 [2]
COMPLETED     11 [3]   6 [4]
NOT COMPLETED     32     47  
Disease Progression                 26                 41  
Study Drug Toxicity                 4                 0  
Withdrawal by Subject                 1                 3  
Adverse Event                 0                 3  
Deterioration/Undocumented Progression                 1                 0  
[1] 2 completed Induction Phase but did not enter Maintenance Phase
[2] 1 completed Induction Phase but did not enter Maintenance Phase
[3] Study is in closure at this time. 11 in Maintenance Phase not yet summarized.
[4] Study is in closure. 6 participants in Maintenance Phase not yet summarized.

Period 4:   Follow-up Phase
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
STARTED     247 [1]   251 [1]
COMPLETED     236     245  
NOT COMPLETED     11     6  
On-going participants still on drug                 11                 6  
[1] All participants received study drug. Follow-up was performed for those leaving earlier phases.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of Randomized Participants

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

Total Total of all reporting groups

Baseline Measures
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine     Total  
Number of Participants  
[units: participants]
  250     252     502  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     165     177     342  
>=65 years     85     75     160  
Age  
[units: years]
Mean ± Standard Deviation
  57.5  ± 13.51     56.4  ± 13.71     57.0  ± 13.61  
Gender  
[units: participants]
     
Female     98     103     201  
Male     152     149     301  
Region of Enrollment  
[units: participants]
     
Australia     5     10     15  
South Africa     10     12     22  
North America     46     46     92  
South America     13     9     22  
Europe     176     175     351  
Melanoma Tumor Stage; Metastasis Classification at Study Entry [1]
[units: Participants]
     
M0     6     8     14  
M1a     37     43     80  
M1b     64     62     126  
M1c     143     139     282  
Eastern Cooperative Oncology Group Performance Status [2]
[units: Participants]
     
Category 0     177     179     356  
Category 1     73     73     146  
[1] Melanoma Tumor Staging: Metastasis (M) classification. M0=No distant metastases; M1a=Distant skin, subcutaneous tissue, or nodal metastases with normal lactic dehydrogenase (LDH); M1b=Lung metastases with normal LDH; M1c=All other visceral metastases with normal LDH or any distant metastasis with elevated LDH. Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma. J Clin Oncol. 2001;19 (16):3635-3648.
[2] Eastern Cooperative Oncology Group Performance Status. Measured from 0 to 5 with 0=fully active; 1=restricted in physically strenuous activity; 2=ambulatory; 3=limited self care; 4= completely disabled; 5=dead. Lower score=better performance.



  Outcome Measures
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1.  Primary:   Overall Survival (OS)   [ Time Frame: Date of randomization to 37 months through 5-year follow-up and up to approximately 76 months ]

Measure Type Primary
Measure Title Overall Survival (OS)
Measure Description OS was defined as the time from the date of randomization until the date of death. Analysis of OS was to be done once 416 deaths had occurred (primary endpoint). However, analysis occurred at 414 deaths (February 7, 2011), due to operational timing of the study. Median number of months of OS and associated confidence interval calculated using the method of Brookmeyer and Crowley.
Time Frame Date of randomization to 37 months through 5-year follow-up and up to approximately 76 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants whose survival follow-up was current (defined as having died or last known alive date occurring on or after the data cutoff date, which was when a total of 414 deaths occurred).

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks then1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  250     252  
Overall Survival (OS)  
[units: Months]
Median ( 95% Confidence Interval )
  11.17  
  ( 9.40 to 13.60 )  
  9.07  
  ( 7.75 to 10.51 )  


Statistical Analysis 1 for Overall Survival (OS)
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.0009
Hazard Ratio (HR) [4] 0.716
95% Confidence Interval ( 0.588 to 0.872 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis stratified for metastasis stage (M0 vs M1a vs M1b vs M1c) and Eastern Cooperative Oncology Group performance status (0 vs 1) recorded at randomization.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  p-value was via stratified log-rank test
[4] Other relevant estimation information:
  Hazard ratio via stratified Cox proportional hazards model.



2.  Secondary:   Survival Rate at 1 Year, 18 Months, 2 Years, and 3 Years   [ Time Frame: Date of randomization to 3 years following randomization ]

Measure Type Secondary
Measure Title Survival Rate at 1 Year, 18 Months, 2 Years, and 3 Years
Measure Description The survival rate (percentage of participants alive) was defined as the probability that a participant is alive at 1 year (or 18 months, 2 years, or 3 years) following randomization and was estimated via the Kaplan-Meier method.
Time Frame Date of randomization to 3 years following randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  250     252  
Survival Rate at 1 Year, 18 Months, 2 Years, and 3 Years  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
   
At 1 year     47.3  
  ( 41.0 to 53.6 )  
  36.3  
  ( 30.4 to 42.4 )  
At 18 months     35.6  
  ( 29.7 to 41.6 )  
  26.1  
  ( 20.7 to 31.6 )  
At 2 years     28.5  
  ( 22.9 to 34.2 )  
  17.9  
  ( 13.3 to 22.8 )  
At 3 years     20.8  
  ( 15.7 to 26.1 )  
  12.2  
  ( 8.2 to 16.5 )  

No statistical analysis provided for Survival Rate at 1 Year, 18 Months, 2 Years, and 3 Years



3.  Secondary:   Disease Control Rate (DCR)   [ Time Frame: First dose to last tumor assessment prior to subsequent therapy at data cutoff for Primary Endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Disease Control Rate (DCR)
Measure Description DCR=number whose best overall response (BOR) was partial response (PR), complete response (CR) or stable disease (SD), divided by all randomized participants (unevaluable participants included). Independent review committee assessment. BOR=date of first dose to last tumor assessment prior to subsequent cancer therapy (including tumor resection, excluding palliative local radiotherapy). Modified World Health Organization criteria: CR=disappearance of all lesions; no evidence of progressive disease (PD); PR=50% or more decrease in the sum of products of the longest diameter and greatest perpendicular diameter of all index lesions compared with baseline; SD=neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD; PD=at least 25% increase in sum of products of all index lesions and/or appearance of any new lesions; nonindex lesions: appearance of any new lesions and/or unequivocal progression of nonindex lesions.
Time Frame First dose to last tumor assessment prior to subsequent therapy at data cutoff for Primary Endpoint (approximately 5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks was continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase. Participants who experienced PD or who did not wish to continue study assessments in the Induction or Maintenance Phases entered the Follow-up Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent. Participants who experienced PD or who did not wish to continue study assessments in the Induction or Maintenance Phases entered the Follow-up Phase.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  250     252  
Disease Control Rate (DCR)  
[units: Percentage of participants]
  33.2     30.2  


Statistical Analysis 1 for Disease Control Rate (DCR)
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.4067
Odds Ratio (OR) [4] 1.179
95% Confidence Interval ( 0.799 to 1.740 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Analysis stratified for metastasis stage (M0 vs M1a vs M1b vs M1c) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1) recorded at randomization.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified for metastasis stage (M0 vs M1a vs M1b vs M1c) and ECOG performance status (0 vs 1) recorded at randomization.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Median Number of Months of Progression-free Survival (PFS)   [ Time Frame: Randomization to date of progression or death to approximately 5 years ]

Measure Type Secondary
Measure Title Median Number of Months of Progression-free Survival (PFS)
Measure Description PFS=time between randomization and date of progression or death, whichever occurs first. Participants who died without reported prior progression were considered to have progressed on date of death. For those alive and not progressed, PFS was censored on date of last evaluable tumor assessment (TA). Those who have not died and have no recorded postbaseline TA were censored at randomization. Those who died without any recorded postbaseline TA were considered to have progressed on date of death. Evaluation was conducted by both investigator and an independent review committee (IRC), who assessed radiologic imaging studies, photographs of skin lesions, and clinical data. Progressive disease defined using modified criteria of the World Health Organization: demonstration of at least a 25% increase in the sum of products of all index lesions or the appearance of any new lesions. For nonindex lesions: appearance of any new lesions or unequivocal progression of nonindex lesions.
Time Frame Randomization to date of progression or death to approximately 5 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10mg/kg, every 12 weeks will be continued until disease progression. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until disease progression (PD), unacceptable toxicity, or withdrawal of consent

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  250     252  
Median Number of Months of Progression-free Survival (PFS)  
[units: Months]
Median ( 95% Confidence Interval )
   
PFS per IRC     2.76  
  ( 2.63 to 3.29 )  
  2.60  
  ( 2.56 to 2.66 )  
PFS per investigator     2.73  
  ( 2.63 to 3.48 )  
  2.63  
  ( 2.60 to 2.73 )  

No statistical analysis provided for Median Number of Months of Progression-free Survival (PFS)



5.  Secondary:   Progression-free Survival (PFS) Rate Truncated at Week 12   [ Time Frame: Day 78 ]

Measure Type Secondary
Measure Title Progression-free Survival (PFS) Rate Truncated at Week 12
Measure Description PFS rate=probability patient was progression-free at Day 78, calculated as total patients receiving treatment and with an overall response of stable disease (SD), partial response (PR), or complete response (CR) at Week 12, divided by total patients. For those alive and not progressed at or before Week 12, PFS censored on date of last evaluable tumor assessment (TA) at or before Week 12. Those with an assessment of PD prior to Week 12 and subsequent assessment of SD, PR, or CR at Week 12 were called progression-free at Week 12. Those with no recorded postbaseline TA dated on or before Day 109, and who had not died on or before Day 109, were censored at randomization. PD=at least 25% increase in sum of products of all index lesions or appearance of any new lesions. Both an investigator and independent review committee (IRC) assessed radiologic imaging studies, photographs of skin lesions, and clinical data. IRC assessment was considered primary over that of the investigators.
Time Frame Day 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks was continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase. Participants who experienced PD or who did not wish to continue study assessments in the Induction or Maintenance Phases entered the Follow-up Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent. Participants who experienced PD or who did not wish to continue study assessments in the Induction or Maintenance Phases entered the Follow-up Phase.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  250     252  
Progression-free Survival (PFS) Rate Truncated at Week 12  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
   
PFS rate at Week 12 by IRC     55.4  
  ( 48.6 to 62.1 )  
  50.7  
  ( 44.2 to 57.3 )  
PFS rate at Week 12 by Investigator     58.5  
  ( 51.9 to 65.0 )  
  54.0  
  ( 47.5 to 60.4 )  

No statistical analysis provided for Progression-free Survival (PFS) Rate Truncated at Week 12



6.  Secondary:   Best Overall Response Rate (BORR)   [ Time Frame: First dose to last tumor assessment at data cutoff for primary endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Best Overall Response Rate (BORR)
Measure Description BORR=number with Best Overall Response (BOR) of complete response (CR) or partial response (PR), divided by total number of randomized patients. BOR=date of first dose to the last tumor assessment prior to subsequent cancer therapy (including tumor resection surgery but excluding palliative local radiotherapy for bone lesions). Independent review committee assessment. Modified criteria of the World Health Organization (mWHO): CR=disappearance of all lesions; no evidence of progressive disease; PR=50% or greater decrease in the sum of products of the longest diameter and greatest perpendicular diameter of all index lesions compared with baseline. Immune-related (ir) response criteria (irRC) assess tumor response in patients on immunotherapy: irCR=disappearance of all lesions in 2 consecutive observations at least 4 weeks apart; irPR=50% or greater decrease in total measureable tumor burden compared with peak in 2 observations at least 4 weeks apart.
Time Frame First dose to last tumor assessment at data cutoff for primary endpoint (approximately 5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1e dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  250     252  
Best Overall Response Rate (BORR)  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
   
BORR by mWHO criteria     15.2  
  ( 11.0 to 20.3 )  
  10.3  
  ( 6.9 to 14.8 )  
BORR by irRC     16.8  
  ( 12.4 to 22.0 )  
  11.1  
  ( 7.5 to 15.7 )  

No statistical analysis provided for Best Overall Response Rate (BORR)



7.  Secondary:   Duration of Response (DOR): Randomized Participants With Response of Complete Response (CR) or Partial Response (PR)   [ Time Frame: Day of CR or PR to day of PD or death up to data cutoff for primary endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Duration of Response (DOR): Randomized Participants With Response of Complete Response (CR) or Partial Response (PR)
Measure Description DOR defined in those with Best Overall Response (BOR)=CR or PR per independent review committee (IRC) as time between date of response of confirmed CR or PR, whichever occurred first, and date of PD or death. If PR assessed before CR, DOR confirmed at earlier time-point showing PR. Modified criteria of the World Health Organization (mWHO): CR=disappearance of all lesions;no evidence of PD; PR=50% or greater decrease in the sum of products of longest and greatest perpendicular diameters (SPD) of all index lesions compared with baseline. PD=an increase of 25% or greater in SPD of index lesions compared with the smallest recorded sum, or appearance of 1 or more new lesions. Immune-related response criteria (irRC): SD=50% decrease in total measurable tumor burden compared with peak cannot be established nor 25% increase compared with nadir, in absence of unequivocal progression of nonindex lesions. Unconfirmed immune-related (ir) CR, irPR, or irPD=irSD.
Time Frame Day of CR or PR to day of PD or death up to data cutoff for primary endpoint (approximately 5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group and had a response of CR, PR, irCR, or irPR. n=number of participants who responded by mWHO criteria and irRC.

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  42     28  
Duration of Response (DOR): Randomized Participants With Response of Complete Response (CR) or Partial Response (PR)  
[units: Months]
Median ( 95% Confidence Interval )
   
Using mWHO criteria (n=38, 26)     19.3  
  ( 12.1 to 26.1 )  
  8.1  
  ( 5.2 to 19.8 )  
Using irRC criteria (n=42, 28)     21.1  
  ( 16.5 to 26.1 )  
  10.2  
  ( 5.6 to 24.0 )  

No statistical analysis provided for Duration of Response (DOR): Randomized Participants With Response of Complete Response (CR) or Partial Response (PR)



8.  Secondary:   Time to Response: All Randomized Participants With Response to Treatment   [ Time Frame: First dose to date of BOR up to data cutoff for primary endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Time to Response: All Randomized Participants With Response to Treatment
Measure Description Time to response was defined as the time between the first dose of study therapy and the date when measurement criteria were met for Best Overall Response (BOR) of partial response (PR) or complete response (CR), whichever occurred first, per independent review committee. Note that if an overall response of PR occurred before confirmation of CR, the time to response endpoint was not determined by the time that the BOR of CR was shown but rather by the earlier time point showing PR. Modified criteria of the World Health Organization: CR=disappearance of all lesions; no evidence of progressive disease (PD); PR=50% or more decrease in the sum of products of the longest and greatest perpendicular diameters (SPD) of all index lesions compared with baseline; PD=an increase of 25% or greater in the SPD of index lesions compared with the smallest recorded sum, or the appearance of 1 or more new lesions.
Time Frame First dose to date of BOR up to data cutoff for primary endpoint (approximately 5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group and who had a response of CR or PR

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression, (PD) unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; one dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  38     26  
Time to Response: All Randomized Participants With Response to Treatment  
[units: Months]
Median ( Full Range )
  2.6  
  ( 2.3 to 3.9 )  
  2.7  
  ( 2.5 to 5.7 )  

No statistical analysis provided for Time to Response: All Randomized Participants With Response to Treatment



9.  Secondary:   Duration of Stable Disease (SD): Randomized Participants With Stable Disease   [ Time Frame: Week 12 to date of disease progression or death up to data cutoff for primary endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Duration of Stable Disease (SD): Randomized Participants With Stable Disease
Measure Description Duration of SD was defined in those whose Best Overall Response (BOR) was SD, per independent review committee (IRC) as the time between Week 12 and date of progressive disease (PD) or death , whichever occurs first. For those who underwent tumor resection following Week 12 but prior to PD, duration of SD was censored on date of last evaluable tumor assessment (TA) prior to resection. For those with BOR of SD at Week 12, date of PD was used in analysis of duration of SD. For those with BOR=SD who have not subsequently progressed and who remain alive, duration of SD censored on date of last evaluable TA. Modified criteria of the World Health Organization (mWHO): SD=insufficient decrease to qualify for partial response or sufficient increase to qualify for PD; PD=an increase of 25% or more in sum of products of longest diameter and greatest perpendicular diameter of index lesions compared with smallest recorded sum, or appearance of 1 or more new lesions.
Time Frame Week 12 to date of disease progression or death up to data cutoff for primary endpoint (approximately 5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group and had SD

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In maintenance phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  45     57  
Duration of Stable Disease (SD): Randomized Participants With Stable Disease  
[units: Months]
Median ( 95% Confidence Interval )
   
Duration of SD by mWHO criteria(n=45, 50)     4.7  
  ( 1.9 to 9.2 )  
  4.6  
  ( 3.2 to 6.9 )  
Duration of SD by IRC criteria (n=45, 57)     4.8  
  ( 2.8 to 7.7 )  
  3.4  
  ( 2.5 to 5.2 )  

No statistical analysis provided for Duration of Stable Disease (SD): Randomized Participants With Stable Disease



10.  Secondary:   Percentage of Participants With Brain Metastasis-Free Survival at Time of Data Cutoff   [ Time Frame: Date of randomization up to data cutoff for primary endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Percentage of Participants With Brain Metastasis-Free Survival at Time of Data Cutoff
Measure Description Brain metastasis-free survival was defined as the time from randomization to the date of progression with a new lesion located in the brain. New brain lesions prior to Week 12 constituted a progression event (unlike main progression-free survival analysis). A participant who dies without documentation of a brain lesion was considered to have progressed with brain metastasis on the date of death. Participants who are free of brain metastasis were censored on the date of their last tumor assessment. An independent review committee evaluated images of participants with clinical symptoms to determine the number of those free of brain metastasis. The brain metastasis-free status was reported as a percent of participants (n/N), where n= participants with metastasis-free brains at data cutoff for the Primary Endpoint and N= randomized participants. A 2-sided Clopper and Pearson confidence interval was performed.
Time Frame Date of randomization up to data cutoff for primary endpoint (approximately 5 years)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  250     252  
Percentage of Participants With Brain Metastasis-Free Survival at Time of Data Cutoff  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
  93.6  
  ( 89.8 to 96.3 )  
  90.9  
  ( 86.6 to 94.1 )  

No statistical analysis provided for Percentage of Participants With Brain Metastasis-Free Survival at Time of Data Cutoff



11.  Secondary:   Number of Participants With Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Hypersensitivity, Immune-related AEs/SAEs, and Inflammatory AEs/SAEs   [ Time Frame: Week 1 (First Dose) to 70 days after last dose of study up to data cutoff for primary endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Number of Participants With Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Hypersensitivity, Immune-related AEs/SAEs, and Inflammatory AEs/SAEs
Measure Description AE=any new undesirable symptom, sign, clinically significant laboratory abnormality, or medical condition occurring after starting study treatment, even if the event was not considered to be drug-related. 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= Potentially Life-threatening or disabling. Randomization=Day 1; start of treatment (first dose)=Week 1. Summarization time frame is from first dose to 70 days after last dose of study at time of 414 deaths.
Time Frame Week 1 (First Dose) to 70 days after last dose of study up to data cutoff for primary endpoint (approximately 5 years)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of randomized ipilimumab or placebo and/or dacarbazine

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10m g/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; one dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  247     251  
Number of Participants With Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Hypersensitivity, Immune-related AEs/SAEs, and Inflammatory AEs/SAEs  
[units: Participants]
   
AEs     244     236  
Drug-related AEs     221     192  
Discontinuations due to AEs     114     46  
SAEs     170     121  
Drug-related SAEs     116     17  
Drug-related hypersensitivity     5     4  
Immune-related AEs     187     77  
Immune-related SAEs     91     3  
Infammatory AEs     201     117  
Inflammatory SAEs     101     9  

No statistical analysis provided for Number of Participants With Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Hypersensitivity, Immune-related AEs/SAEs, and Inflammatory AEs/SAEs



12.  Secondary:   Number of Participants With Grade 2-3 and Grade 3-4 Immune-related Adverse Events (irAEs) With Resolution Resolved   [ Time Frame: Week 1 (first dose) to 70 days after last dose up to data cutoff for primary endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Number of Participants With Grade 2-3 and Grade 3-4 Immune-related Adverse Events (irAEs) With Resolution Resolved
Measure Description irAEs included the categories: gastrointestinal (GI), diarrhea, liver, endocrine, and skin. Grade 2=moderate adverse events (AEs); minimal, local, or noninvasive intervention indicated. Grade 3=severe AEs, medically significant but not immediately life-threatening. Grade 4=life-threatening consequences; urgent intervention indicated. Resolution is defined as improvement to Grade 1 or less or to the Grade at baseline (prior to treatment).
Time Frame Week 1 (first dose) to 70 days after last dose up to data cutoff for primary endpoint (approximately 5 years)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of study drug and had this specific event

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks was continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase. Participants who experienced PD or who did not wish to continue study assessments in the Induction or Maintenance Phases entered the Follow-up Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent. Participants who experienced PD or who did not wish to continue study assessments in the Induction or Maintenance Phases entered the Follow-up Phase.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  89     8  
Number of Participants With Grade 2-3 and Grade 3-4 Immune-related Adverse Events (irAEs) With Resolution Resolved  
[units: Participants]
   
GI AE Grade 2-4 (n=39, 7)     36     7  
GI Grade 3-4 (n=14, 0)     13     0  
Liver AE Grade 2-4 (n=89, 8)     81     4  
Liver AE Grade 3-4 (n=69, 5)     63     2  
Skin AE Grade 2-4 (n=46, 2)     42     2  
Skin AE Grade 3-4 (n=8, 0)     6     0  
Diarrhea AE Grade 2-3 (n=31, 7)     29     7  
Diarrhea AE Grade 3-4 (n=10, 0)     9     0  

No statistical analysis provided for Number of Participants With Grade 2-3 and Grade 3-4 Immune-related Adverse Events (irAEs) With Resolution Resolved



13.  Secondary:   Time to Resolution of Grade 2-3, Grade 3-4 Immune-related Adverse Events (irAEs)   [ Time Frame: Week 1 (first dose) to 70 days after last dose up to database lock for primary endpoint (approximately 5 years) ]

Measure Type Secondary
Measure Title Time to Resolution of Grade 2-3, Grade 3-4 Immune-related Adverse Events (irAEs)
Measure Description irAEs included the categories: gastrointestinal (GI), diarrhea, liver, endocrine, and skin. Grade 2=Moderate adverse events (AEs); minimal, local or noninvasive intervention indicated. Grade 3=severe AEs, medically significant but not immediately life-threatening. Grade 4=life-threatening consequences; urgent intervention indicated. Time to resolution is defined as improvement to Grade 1 or less or to the Grade at baseline (prior to treatment).
Time Frame Week 1 (first dose) to 70 days after last dose up to database lock for primary endpoint (approximately 5 years)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of study drug and had a specific event that resolved

Reporting Groups
  Description
Ipilimumab and Dacarbazine

Ipilimumab: Intravenous solution; intravenous; 10 mg/kg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24, until disease progression (PD), unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.

In Maintenance Phase: Only Ipilimumab: 10 mg/kg, every 12 weeks will be continued until PD. Dacarbazine was given up to Week 22 and was not given in the Maintenance Phase.

Placebo and Dacarbazine

Placebo: Intravenous solution; intravenous; 0 mg; 1 dose every 3 weeks for 10 weeks, then 1 dose every 12 weeks starting at Week 24; until PD, unacceptable toxicity, or withdrawal of consent.

Dacarbazine: Intravenous solution; intravenous; 850 mg/m^2; 1 dose every 3 weeks for 22 weeks, until PD, unacceptable toxicity, or withdrawal of consent.


Measured Values
    Ipilimumab and Dacarbazine     Placebo and Dacarbazine  
Number of Participants Analyzed  
[units: participants]
  81     7  
Time to Resolution of Grade 2-3, Grade 3-4 Immune-related Adverse Events (irAEs)  
[units: Weeks]
Median ( 95% Confidence Interval )
   
GI AE Grade 2-4 (n=36, 7)     2.00  
  ( 1.14 to 2.71 )  
  0.14  
  ( 0.14 to 0.29 )  
GI Grade 3-4 (n=13, 0))     2.14  
  ( 2.00 to 4.57 )  
  NA  
  ( NA to NA ) [1]
Liver AE Grade 2-4 (n=81, 4)     3.43  
  ( 3.14 to 4.43 )  
  NA  
  ( 6.86 to NA ) [1]
Liver AE Grade 3-4 (n=63, 2)     3.43  
  ( 3.00 to 4.43 )  
  NA  
  ( 3.57 to NA ) [1]
Skin AE Grade 2-4 (n=42, 2)     4.14  
  ( 3.14 to 7.00 )  
  0.93  
  ( 0.57 to 1.29 )  
Skin AE Grade 3-4 (n=6, 0)     4.71  
  ( 3.14 to 5.29 )  
  NA  
  ( NA to NA ) [1]
Diarrhea AE Grade 2-3 (n=29, 7)     1.43  
  ( 0.71 to 2.57 )  
  0.14  
  ( 0.14 to 0.29 )  
Diarrhea AE Grade 3-4 (n=9, 0)     2.00  
  ( 0.71 to 2.57 )  
  NA  
  ( NA to NA ) [1]
[1] Median time to resolution could not be computed due to low/no occurrence of either the resolution of the AE or low/no occurrence the AE in this arm

No statistical analysis provided for Time to Resolution of Grade 2-3, Grade 3-4 Immune-related Adverse Events (irAEs)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00324155     History of Changes
Other Study ID Numbers: CA184-024
Study First Received: May 8, 2006
Results First Received: January 22, 2014
Last Updated: October 24, 2014
Health Authority: United States: Food and Drug Administration