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Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01668784
First received: August 16, 2012
Last updated: April 28, 2016
Last verified: April 2016
Results First Received: March 28, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Advanced or Metastatic (Medically or Surgically Unresectable) Clear-cell Renal Cell Carcinoma
Interventions: Biological: Nivolumab
Drug: Everolimus

  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
1054 participants enrolled, 821 participants randomized (410 nivolumab, 411 everolimus). Reasons for non-randomization include 9 participants had adverse events, 15 participants withdrew consent, 2 participants died, 1 participant lost to follow-up, 193 participants no longer met study criteria, and 13 participants for other non-listed reasons.

Reporting Groups
  Description
Nivolumab Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.

Participant Flow for 2 periods

Period 1:   Randomized (Pre-treatment)
    Nivolumab   Everolimus
STARTED   410   411 
COMPLETED   406   397 
NOT COMPLETED   4   14 
Disease Progression                0                1 
Request to Discontinue Study Treatment                0                3 
Withdrawal by Subject                1                8 
Poor/Non-Compliance                1                0 
No Longer Meets Study Criteria                2                1 
Not Specified                0                1 

Period 2:   Treated (Overall)
    Nivolumab   Everolimus
STARTED   406   397 
COMPLETED   67   28 
NOT COMPLETED   339   369 
Disease Progression                285                273 
Study Drug Toxicity                35                53 
Death                1                1 
Adverse Event Unrelated to Study Drug                9                14 
Request to Discontinue Study Treatment                5                18 
Withdrawal by Subject                2                3 
Maximal Clinical Benefit                2                3 
Not Specified                0                4 



  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 randomized participants; any participants that was randomized to any treatment group in the study.

Reporting Groups
  Description
Nivolumab Nivolumab at 3 mg/kg solution provided intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Everolimus Everolimus provided in 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.
Total Total of all reporting groups

Baseline Measures
   Nivolumab   Everolimus   Total 
Overall Participants Analyzed 
[Units: Participants]
 410   411   821 
Age 
[Units: Years]
Mean (Standard Deviation)
 60.6  (10.87)   61.9  (10.43)   61.3  (10.66) 
Age, Customized 
[Units: Participants]
     
< 65 years   257   240   497 
>= 65 and < 75   119   131   250 
>= 75 years   34   40   74 
Gender 
[Units: Participants]
     
Female   95   107   202 
Male   315   304   619 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   353   367   720 
Black or African American   1   4   5 
Asian   42   32   74 
American Indian or Alaska Native   1   0   1 
Native Hawaiian or Other Pacific Islander   0   1   1 
Other   13   7   20 
Baseline MSKCC Risk Group (IVRS) [1] 
[Units: Participants]
     
Favorable   145   148   293 
Intermediate   201   203   404 
Poor   64   60   124 
[1] A prognostic model used to assess pretreatment clinical features that are predictive of survival. The Memorial Sloan-Kettering Cancer Center (MSKCC) risk system stratifies patients into poor-, intermediate- and favorable-risk categories based on the number of adverse clinical and laboratory parameters present. An Interactive Voice Response System (IVRS) was used to record responses.
Region 
[Units: Participants]
     
US/Canada   174   172   346 
Western Europe   140   141   281 
Rest of World (ROW)   96   98   194 
Number of Prior Anti-Angiogenic Agents Received in the Advanced/Metastatic Setting 
[Units: Participants]
     
 294   297   591 
 116   114   230 
PD-L1 Expression 
[Units: Participants]
     
PD-L1 Quantifiable >=1%   94   87   181 
PD-L1 Quantifiable <1%   276   299   575 
PD-L1 Indeterminate/Not Evaluable   40   25   65 


  Outcome Measures
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1.  Primary:   Overall Survival (OS) at Primary Endpoint   [ Time Frame: Randomization until 398 deaths, up to May 2015 (approximately 30 months) ]

2.  Secondary:   Investigator-assessed Objective Response Rate (ORR) at Primary Endpoint   [ Time Frame: At 8 weeks post randomization, every 8 weeks for 12 months, and every 12 weeks until date of disease progression or death, up to May 2015 (approximately 30 months) ]

3.  Secondary:   Investigator-assessed Duration of Objective Response at Primary Endpoint   [ Time Frame: From date of first response to date of disease progression or death or censoring if no progression or death occurred, up to May 2015 (approximately 30 months) ]

4.  Secondary:   Investigator-assessed Time to Objective Response at Primary Endpoint   [ Time Frame: Randomization to date of first response, up to May 2015 (approximately 30 months) ]

5.  Secondary:   Investigator-assessed Time of Progression-free Survival (PFS) at Primary Endpoint   [ Time Frame: Randomization until 398 deaths, up to May 2015 (approximately 30 months) ]

6.  Secondary:   Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level at Primary Endpoint   [ Time Frame: Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months) ]

7.  Secondary:   Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events at Primary Endpoint   [ Time Frame: Day of first dose to 30 days post final dose, up to May 2015 (approximately 30 months) ]

8.  Secondary:   Percentage of Participants With Disease-related Symptom Progression (DRSP) at Primary Endpoint   [ Time Frame: Randomization until 398 deaths, up to May 2015 (approximately 30 months) ]

9.  Secondary:   Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests at Primary Endpoint   [ Time Frame: Day 1 to 30 days post last dose, up to May 2015 (approximately 30 months) ]

10.  Secondary:   Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units   [ Time Frame: Day 1 to 30 days post last dose, up to May 2015 (approximately 30 months) ]


  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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01668784     History of Changes
Other Study ID Numbers: CA209-025
2011‐005132‐26 ( EudraCT Number )
Study First Received: August 16, 2012
Results First Received: March 28, 2016
Last Updated: April 28, 2016
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
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Finland: Finnish Medicines Agency
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Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
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Italy: Ministry of Health
Israel: Israeli Health Ministry Pharmaceutical Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
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Poland: National Institute of Medicines
Portugal: National Pharmacy and Medicines Institute
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Russia: Ministry of Health of the Russian Federation
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United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency