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Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01783938
First received: February 1, 2013
Last updated: April 11, 2016
Last verified: April 2016
Results First Received: March 11, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Advanced or Metastatic Melanoma
Interventions: Biological: Nivolumab
Biological: Ipilimumab

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
177 enrolled, 140 randomized (70 to each arm). Reasons for non-randomization=1 adverse event, 1 withdrew consent, 32 no longer met study criteria, 3 for other non-specified reasons. 138 treated (68 nivo-ipi, 70 ipi-nivo). Reasons for non-treatment=1 adverse event unrelated to study drugs, 1 no longer met study criteria. Two cohorts of participants

Reporting Groups
  Description
Nivolumab Followed by Ipilimumab Participants received nivolumab solution at 3 milligram/kilogram (mg/kg) intravenously every 2 weeks for up to 6 doses during Weeks 1 to 13 in Induction Period 1, followed by ipilimumab solution at 3 mg/kg intravenously every 3 weeks for up to 4 doses during Weeks 13 to 25 in Induction Period 2. Per protocol, a participant was allowed to permanently discontinue one agent and then receive the other agent. Participants received nivolumab solution at 3 mg/kg intravenously every 2 weeks, starting at week 25 in the continuation period, for a maximum of 2 years from 1st study treatment in Induction Period 1. At end of 2 years, participants who had investigator-assessed benefit and were tolerating therapy were allowed to continue nivolumab therapy in the Extension Period. Regimen followed until disease progression, unacceptable toxicity, or withdrawal of consent. Treatment Period includes induction period 1, 2, continuation, and extension period.
Ipilimumab Followed by Nivolumab Participants received ipilimumab solution at 3 milligram/kilogram (mg/kg) intravenously every 3 weeks for up to 4 doses during Weeks 1 to 13 in Induction Period 1, followed by nivolumab solution at 3 mg/kg intravenously every 2 weeks for up to 6 doses during Weeks 13 to 25 in Induction Period 2. Per protocol, a participant was allowed to permanently discontinue one agent and then receive the other agent. Participants received nivolumab solution at 3 mg/kg intravenously every 2 weeks, starting at week 25 in the continuation period, for a maximum of 2 years from 1st study treatment in Induction Period 1. At end of 2 years, participants who had investigator-assessed benefit and were tolerating therapy were allowed to continue nivolumab therapy in the Extension Period. Regimen followed until disease progression, unacceptable toxicity, or withdrawal of consent. Treatment Period includes induction period 1, 2, continuation, and extension period.

Participant Flow:   Overall Study
    Nivolumab Followed by Ipilimumab   Ipilimumab Followed by Nivolumab
STARTED   68   70 
COMPLETED   21 [1]   17 [1] 
NOT COMPLETED   47   53 
Disease Progression                18                39 
Study Drug Toxicity                22                10 
Adverse Event Unrelated to Study Drug                2                2 
Request to Discontinue Study Treatment                1                2 
Withdrew Consent                3                0 
Not Specified                1                0 
[1] Completed=continuing treatment; did not permanently discontinue both study drugs in treatment period



  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.
All treated participants; All participants who received at least one dose of any study therapy.

Reporting Groups
  Description
Nivolumab Followed by Ipilimumab Participants received nivolumab solution at 3 milligram/kilogram (mg/kg) intravenously every 2 weeks for up to 6 doses during Weeks 1 to 13 in Induction Period 1, followed by ipilimumab solution at 3 mg/kg intravenously every 3 weeks for up to 4 doses during Weeks 13 to 25 in Induction Period 2. Per protocol, a participant was allowed to permanently discontinue one agent and then receive the other agent. Participants received nivolumab solution at 3 mg/kg intravenously every 2 weeks, starting at week 25 in the continuation period, for a maximum of 2 years from 1st study treatment in Induction Period 1. At end of 2 years, participants who had investigator-assessed benefit and were tolerating therapy were allowed to continue nivolumab therapy in the Extension Period. Regimen followed until disease progression, unacceptable toxicity, or withdrawal of consent. Treatment Period includes induction period 1, 2, continuation, and extension period.
Ipilimumab Followed by Nivolumab Participants received ipilimumab solution at 3 milligram/kilogram (mg/kg) intravenously every 3 weeks for up to 4 doses during Weeks 1 to 13 in Induction Period 1, followed by nivolumab solution at 3 mg/kg intravenously every 2 weeks for up to 6 doses during Weeks 13 to 25 in Induction Period 2. Per protocol, a participant was allowed to permanently discontinue one agent and then receive the other agent. Participants received nivolumab solution at 3 mg/kg intravenously every 2 weeks, starting at week 25 in the continuation period, for a maximum of 2 years from 1st study treatment in Induction Period 1. At end of 2 years, participants who had investigator-assessed benefit and were tolerating therapy were allowed to continue nivolumab therapy in the Extension Period. Regimen followed until disease progression, unacceptable toxicity, or withdrawal of consent. Treatment Period includes induction period 1, 2, continuation, and extension period.
Total Total of all reporting groups

Baseline Measures
   Nivolumab Followed by Ipilimumab   Ipilimumab Followed by Nivolumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 68   70   138 
Age 
[Units: Years]
Mean (Standard Deviation)
 59.1  (14.08)   60.6  (15.17)   59.8  (14.61) 
Age, Customized 
[Units: Participants]
     
Categorization I, <65 years   42   40   82 
Categorization I, >=65 years   26   30   56 
Age, Customized 
[Units: Participants]
     
Categorization II, <65 years   42   40   82 
Categorization II, >=65 and <75 years   19   18   37 
Categorization II, >=75 years   7   12   19 
Gender 
[Units: Participants]
     
Female   22   24   46 
Male   46   46   92 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   65   66   131 
Black or African American   1   2   3 
Asian   0   0   0 
American Indian or Alaska Native   0   0   0 
Native Hawaiian or Other Pacific Islander   0   0   0 
Other   2   2   4 
Region of Enrollment 
[Units: Participants]
     
United States   68   70   138 
Subtype of Disease 
[Units: Participants]
     
Mucosal   5   2   7 
Cutaneous   52   55   107 
Acral   1   4   5 
Ocular/Uveal   6   6   12 
Other   4   3   7 
Baseline Lactate Dehydrogenase (LDH) Level 
[Units: Participants]
     
Upper limit of normal (ULN) or lower   45   41   86 
Higher than ULN   23   29   52 
Higher than 2*ULN   9   12   21 
History of Brain Metastases 
[Units: Participants]
     
Yes   9   2   11 
No   53   60   113 
Not Reported   6   8   14 
B-Raf proto-oncogene (BRAF) Status 
[Units: Participants]
     
Mutant   19   20   39 
Wildtype   44   43   87 
Not Reported   5   7   12 
Eastern Cooperative Oncology Group (ECOG) Performance Status [1] 
[Units: Participants]
     
 47   37   84 
 21   33   54 
[1] ECOG is a 6-item scale used to assess disease progression, daily functioning, appropriate treatment, and prognosis. Performance status is scored on a scale ranging from 0-5, with (best score) 0=fully active and able to carry on all pre-disease performance without restriction and (worst score) 5=death.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Treatment-related Grade 3-5 Adverse Events (AEs) During the Induction Periods   [ Time Frame: Day 1 up to Week 25 ]

2.  Secondary:   Investigator-assessed Response Rate at Week 25   [ Time Frame: Week 25 ]

3.  Secondary:   Investigator-assessed Duration of Response (DOR)   [ Time Frame: Week 25 up to date of disease progression or death, up to approximately 2 years ]

4.  Secondary:   Investigator-assessed Rate of Progression   [ Time Frame: Week 13; Week 25 ]


  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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  More Information
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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



Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01783938     History of Changes
Other Study ID Numbers: CA209-064
Study First Received: February 1, 2013
Results First Received: March 11, 2016
Last Updated: April 11, 2016
Health Authority: United States: Food and Drug Administration