Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma
- Conditions
- Melanoma
- Interventions
- Biological: BMS-936558 (Nivolumab)Biological: Placebo matching BMS-936558 (Nivolumab)
- Registration Number
- NCT01721772
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 418
- 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
- Active brain metastases or leptomeningeal metastases
- Ocular melanoma
- Any active, known, or suspected autoimmune disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nivolumab, 3 mg/kg Placebo matching Dacarbazine Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion. Eligible participants may switch to nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends. Nivolumab, 3 mg/kg BMS-936558 (Nivolumab) Participants received nivolumab, 3 mg/kg, solution administered Intravenously (IV) every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion. Eligible participants may switch to nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends. Dacarbazine, 1000 mg/m^2 Placebo matching BMS-936558 (Nivolumab) Participants received dacarbazine, 1000 mg/m\^2, solution administered IV every 3 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion. Eligible participants may cross-over to nivolumab open label treatment, either 3 mg/kg every 2 weeks or 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends. Dacarbazine, 1000 mg/m^2 Dacarbazine Participants received dacarbazine, 1000 mg/m\^2, solution administered IV every 3 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent, or study completion. Eligible participants may cross-over to nivolumab open label treatment, either 3 mg/kg every 2 weeks or 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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 up to 17 months. OS is defined as the time between the date of randomization and the date of death or the last date the participant was known to be alive.
Overall Survival (OS) Rate From randomization to 6 months and or to 12 months OS rate is calculated as the percentage of participants alive at the indicated timepoints
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) 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 94 months ORR is defined as the percentage of participants with a best overall response of Response Evaluation Criteria in Solid Tumors (RECIST) defined complete response (CR) or partial response (PR). 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.
Progression-free Survival (PFS) From date of randomization up to date of disease progression or death, up to approximately 84 months 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 documented on the date of their last evaluable tumor assessment. Patients who did not have any on-study tumor assessments and did not die were documented on their date of randomization. Those who started any subsequent anticancer therapy without a prior reported progression were documented on the date of their last evaluable tumor assessment prior to initiation of subsequent anticancer therapy.
Progression-free Survival (PFS) Rate From randomization to the specified timepoints, up to 84 months 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.
Change From Baseline in Health-related Quality of Life (HRQoL) Scores At baseline and every 6 weeks for 12 months and at follow-up visits 1 and 2, assessed up to 93 months 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.
Overall Survival by Programmed Cell Death Ligand 1 (PD-L1) Expression Level From date of randomization to date of disease progression or death, up to approximately 94 months Overall Survival is defined as the time between the date of randomization and the date of death or the last date the participant was known to be alive. PD-L1 expression level is 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 (immunohistochemistry) 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% (PD-L1 positive) versus patients with tumor PD-L1 expression \<5% (PD-L1 negative). Tumor tissue samples for PD-L1 testing were collected at screening from metastatic or unresectable sites prior to randomization.
Trial Locations
- Locations (29)
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Local Institution - 0013
🇫🇷Villejuif, France
Local Institution - 0035
🇫🇮Helsinki, Finland
Greenslopes Private Hospital
🇦🇺Greenslopes, Queensland, Australia
Hopital Saint Andre
🇫🇷Bordeaux, France
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Chu Grenoble - Hopital Albert Michallon
🇫🇷Grenoble, France
Hopital St Eloi
🇫🇷Montpellier, France
Local Institution - 0056
🇪🇸Barcelona, Spain
Aarhus Universitetshospital
🇩🇰Aarhus, Denmark
Herlev Hospital
🇩🇰Herlev, Denmark
Odense University Hospital
🇩🇰Odense, Denmark
Fundacion Cidea
🇦🇷Buenos Aires, Distrito Federal, Argentina
Instituto Oncologico De Cordoba
🇦🇷Cordoba, Argentina
Local Institution
🇸🇪Umea, Sweden
Chru De Lille - Hopital Claude Huriez
🇫🇷Lille, France
Coffs Harbour Health Campus
🇦🇺Coffs Harbour, New South Wales, Australia
Local Institution - 0006
🇦🇺North Sydney, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Hopital Saint Louis
🇫🇷Paris, France
Instituto Medico Especialazado Alexander Fleming
🇦🇷Buenos Aires, Argentina
Local Institution - 0040
🇨🇦Montreal, Quebec, Canada
Laiko Hospital
🇬🇷Athens, Greece
Metropolitan Hospital
🇬🇷Neo Faliro, Greece
Qe Ii Health Science Centre
🇨🇦Halfax, Nova Scotia, Canada
Cabrini Hospital
🇦🇺Malvern, Victoria, Australia
Local Institution - 0039
🇨🇦Vancouver, British Columbia, Canada