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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

November 2, 2012
January 27, 2016
January 2013
June 2014   (final data collection date for primary outcome measure)
  • 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. ] [ Designated as safety issue: No ]
    OS is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.
  • Overall Survival (OS) Rate [ Time Frame: Randomization to 6 months and 12 months ] [ Designated as safety issue: No ]
    OS rate is calculated as the percentage of participants who have not died divided by the total number of participants in the arm, based on Kaplan-Meier estimates
Endpoint of Overall survival (OS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
OS is defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive
Complete list of historical versions of study NCT01721772 on ClinicalTrials.gov Archive Site
  • Progression-free Survival (PFS) [ Time Frame: From date of randomization to date of disease progression or death, assessed to 17 months ] [ Designated as safety issue: No ]

    Investigator-assessed PFS is defined as the time from randomization to the date of the first documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Patients who died without progressing were considered to have progressed on the date of their death.

    Those who did not progress or die were censored on the date of their last evaluable tumor assessment. Patients who did not have any on-study tumor assessments and did not die were censored on their date of randomization. Those who started any subsequent anticancer therapy without a prior reported progression were censored on the date of their last evaluable tumor assessment prior to initiation of subsequent anticancer therapy.

  • 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 ] [ Designated as safety issue: No ]
    The PFS rate at a time point is the estimated percentage of patients who have not progressed and are alive at that time point following randomization and is estimated using the Kaplan-Meier methodology.
  • 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 ] [ Designated as safety issue: No ]
    ORR is defined as the percentage of participants with a best overall response of RECIST-defined complete response (CR) or partial response (PR) divided by the number of randomized participants in each treatment arm. RECIST, volume 1.1 for target lesions: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of the longest dimension (LD) of target lesions, taking as reference the baseline sum LD; stable disease=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, and the sum LD must have an absolute increase of ≥5 mm.
  • 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 ] [ Designated as safety issue: No ]
    Overall Survival by PD-L1 expression level, which was defined as the percent of tumor cells demonstrating plasma membrane PD-L1-staining in a minimum of 100 evaluable tumor cells per a Dako PD-L1 IHC assay (referred to as quantifiable PD-L1 expression). Assessment of OS by PD-L1 expression as measured by a validated assay and comparing OS in patients with tumor PD-L1 expression ≥5% versus patients with tumor PD-L1 expression <5%. Tumor tissue samples for PD-L1 testing were collected at screening from metastatic or unresectable sites prior to randomization.
  • 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 ] [ Designated as safety issue: No ]
    HRQoL is evaluated by mean changes from baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/quality of life composite scale in all randomized patients. The QLQ-30 is a cancer-specific, self-administered questionnaire that contains 30 questions, covering global, functional, and symptom scales. Scores range from 0 to 100. Higher scores on global and functional scales indicate better quality of life (QoL), while higher scores on the symptom scales indicate declining QoL.
  • Progression-free Survival (PFS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    PFS is defined as the time from randomization to the date of the first documented progression, as determined by the investigator, or death due to any cause, whichever occurs first
  • Objective Response Rate (ORR) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    ORR is defined as the number of subjects with a Best Overall Response (BOR) of Complete Response (CR) or Partial response (PR) divided by the number of randomized subjects for each treatment arm
  • Programmed death-ligand 1 (PD-L1) expression as predictive biomarker [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    PD-L1 expression as measured by the endpoint OS based on PD-L1 expression level
  • Health Related Quality of Life (HRQoL) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

    HRQoL as measured by mean changes from baseline in the EORTC-QLQ-C30 global health status/QoL composite scale and by mean changes from baseline in the remaining EORTC QLQ-C30 scales in all randomized subjects;

    EORTC-QLQ-C30 = European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Core 30

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 ] [ Designated as safety issue: Yes ]
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. Drug-related=having certain, probable, possible, or unknown relationship to study drug.
Not Provided
 
Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma
A Phase 3, Randomized, Double-Blind Study of BMS-936558 vs Dacarbazine in Subjects With Previously Untreated, Unresectable or Metastatic Melanoma
The purpose of this study is to compare the clinical benefit, as measured by overall survival, of nivolumab with that of. dacarbazine in patients with previously untreated, unresectable, or metastatic melanoma
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Melanoma
  • Biological: BMS-936558 (Nivolumab)
  • Biological: Placebo matching BMS-936558 (Nivolumab)
  • Drug: Dacarbazine
  • Drug: Placebo matching Dacarbazine
  • Experimental: 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
    Interventions:
    • Biological: BMS-936558 (Nivolumab)
    • Drug: Placebo matching Dacarbazine
  • Active Comparator: 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
    Interventions:
    • Biological: Placebo matching BMS-936558 (Nivolumab)
    • Drug: Dacarbazine
Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015 Jan 22;372(4):320-30. doi: 10.1056/NEJMoa1412082. Epub 2014 Nov 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
583
June 2014
June 2014   (final data collection date for primary outcome measure)

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Men and women ≥18 years of age
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Untreated and histologically confirmed unresectable Stage III or Stage IV melanoma, as per the staging system of the American Joint Committee on Cancer
  • Measurable disease as per Response Evaluation Criteria in Solid Tumors 1.1
  • Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses
  • Known BRAF wild-type, as per regionally acceptable V600 mutational status testing. BRAF mutant patients and those with indeterminate or unknown BRAF status are not permitted to randomize

Exclusion Criteria:

  • Active brain metastases or leptomeningeal metastases
  • Ocular melanoma
  • Any active, known, or suspected autoimmune disease
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Canada,   Chile,   Denmark,   Finland,   France,   Germany,   Greece,   Israel,   Italy,   Mexico,   Norway,   Poland,   Spain,   Sweden
United States
 
NCT01721772
CA209-066, 2012‐003718‐16
Yes
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP