Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma (CheckMate 066)

This study has been terminated.
(The study was terminated early due to the clear benefit of nivolumab on survival)
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01721772
First received: November 2, 2012
Last updated: January 27, 2016
Last verified: November 2015
Results First Received: November 20, 2015  
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: Biological: BMS-936558 (Nivolumab)
Biological: Placebo matching BMS-936558 (Nivolumab)
Drug: Dacarbazine
Drug: Placebo matching 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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 583 participants enrolled, 418 were randomized (210 to nivolumab, 208 to dacarbazine) and 411 received treatment (206 with nivolumab, 205 with dacarbazine).

Reporting Groups
  Description
Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion

Participant Flow:   Overall Study
    Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine     Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab  
STARTED     206     205  
COMPLETED     95 [1]   13 [1]
NOT COMPLETED     111     192  
Disease progression                 96                 175  
Study drug toxicity                 5                 7  
Unrelated adverse event                 2                 3  
Withdrawal by Subject                 7                 5  
Maximum clinical benefit                 1                 1  
Not specified                 0                 1  
[1] Continuing 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 participants randomized to receive treatment

Reporting Groups
  Description
Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks with placebo-matching dacarbazine solution administered IV every 3 weeks, until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab Participants received dacarbazine 1000 mg/m^2, solution administered IV every 3 weeks with placebo-matching nivolumab solution administered IV every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion
Total Total of all reporting groups

Baseline Measures
    Nivolumab, 3 mg/kg + Placebo-matching Dacarbazine     Dacarbazine, 1000 mg/m^2 + Placebo-matching Nivolumab     Total  
Number of Participants  
[units: participants]
  210     208     418  
Age  
[units: Years]
Mean (Standard Deviation)
  61.6  (13.00)     63.7  (12.60)     62.7  (12.83)  
Age, Customized  
[units: Participants]
     
Younger than 65 years     106     94     200  
65 to younger than 75 years     77     74     151  
75 years and older     27     40     67  
Gender  
[units: Participants]
     
Female     89     83     172  
Male     121     125     246  
Race/Ethnicity, Customized  
[units: Participants]
     
White     209     207     416  
Black or African American     0     0     0  
Asian     0     1     1  
American Indian or Alaskan native     0     0     0  
Other     1     0     1  
M-stage at study entry [1]
[units: Participants]
     
M0     17     13     30  
M1a     21     20     41  
M1b     44     48     92  
M1c     128     127     255  
Stratification programmed cell death ligand 1 status  
[units: Participants]
     
Positive     74     74     148  
Negative/indeterminate     136     134     270  
Time from initial diagnosis  
[units: Years]
Median (Full Range)
  1.93   (0.1 to 32.6)     1.65   (0.1 to 22.2)     1.83   (0.1 to 32.6)  
Participants with at least 1 lesion  
[units: Participants]
  209     208     417  
Site of lesion  
[units: Participants]
     
Bone     25     18     43  
Intestine     6     3     9  
Liver     68     60     128  
Lung     128     125     253  
Lymph node     120     121     241  
Other     54     47     101  
Skin     23     37     60  
Soft tissue     40     58     98  
Visceral, other     30     50     80  
[1] M-stage=melanoma stage by American Joint Committee on Cancer Melanoma Staging and Classification, 2009. M0=no distant metastases; M1a=distant skin, subcutaneous, or nodal metastases; M1b=lung metastases; M1c=all other visceral metastases



  Outcome Measures
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1.  Primary:   Overall Survival (OS)   [ Time Frame: From date of randomization to date of death. For those without documentation of death, to the last date the participant was known to be alive, assessed to 17 months. ]

2.  Primary:   Overall Survival (OS) Rate   [ Time Frame: Randomization to 6 months and 12 months ]

3.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: From date of randomization to date of disease progression or death, assessed to 17 months ]

4.  Secondary:   Progression-free Survival (PFS) Rate   [ Time Frame: Tumor assessments beginning at 9 weeks following randomization and continuing every 6 weeks for the first year, then every 12 weeks thereafter until disease progression or death, assessed to 17 months ]

5.  Secondary:   Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST)   [ Time Frame: Tumor assessments beginning at 9 weeks following randomization and continuing every 6 weeks for the first year, then every 12 weeks thereafter until disease progression or death, assessed to 17 months ]

6.  Secondary:   Overall Survival by Programmed Cell Death Ligand 1 (PD-L1) Expression Level   [ Time Frame: From date of randomization to date of disease progression or death, as assessed to 17 months ]

7.  Secondary:   Change From Baseline in Health-related Quality of Life (HRQoL) Scores   [ Time Frame: At baseline and every 6 weeks for 12 months and at follow-up visits 1 and 2, assessed up to 17 months ]

8.  Other Pre-specified:   Number of Participants Who Died and With Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, and Drug-related AEs   [ Time Frame: Day of first dose to day of final dose + 30 days, assessed up go 17 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
An independent data monitoring committee (DMC) found that data from a DMC-requested database lock showed clear survival benefit with nivolumab and thus recommended unblinding the study and switching patients randomized to dacarbazine to nivolumab.


  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: NCT01721772     History of Changes
Other Study ID Numbers: CA209-066
2012‐003718‐16 ( EudraCT Number )
Study First Received: November 2, 2012
Results First Received: November 20, 2015
Last Updated: January 27, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Canada: Health Canada
Denmark: Danish Dataprotection Agency
Finland: Laakelaitos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Ireland: Irish Medicines Board
Italy: Ministry of Health
Israel: Israeli Health Ministry Pharmaceutical Administration
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Data Inspectorate Directorate for Health and Social Affairs
Poland: National Institute of Medicines
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency