Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma (CheckMate 066)
Biological: BMS-936558 (Nivolumab)
Biological: Placebo matching BMS-936558 (Nivolumab)
Drug: Placebo matching Dacarbazine
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase 3, Randomized, Double-Blind Study of BMS-936558 vs Dacarbazine in Subjects With Previously Untreated, Unresectable or Metastatic Melanoma|
- 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
- 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.
- 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.
|Study Start Date:||January 2013|
|Study Completion Date:||June 2014|
|Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
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
|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
|Biological: Placebo matching BMS-936558 (Nivolumab) Drug: Dacarbazine|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01721772
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|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|