NCT01721772 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2022-07-12

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

Progression-free Survival (PFS)

→

outcome · POSTED

Progression-free Survival (PFS) Rate

→

outcome · POSTED

Objective Response Rate (ORR)

→

outcome · POSTED

Overall Survival by Programmed Cell Death Ligand 1 (PD-L1) Expression Level

→

outcome · POSTED

Overall Survival (OS) Rate

→

outcome · POSTED

Change From Baseline in Health-related Quality of Life (HRQoL) Scores

→

outcome · POSTED

Overall Survival (OS) Extended

→

outcome · POSTED

Overall Survival (OS) Rate Extended

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Biological: BMS-936558 (Nivolumab)
Drug: Placebo matching Dacarbazine
label
Nivolumab, 3 mg/kg
type
EXPERIMENTAL
description
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.
intervention Names
Biological: Placebo matching BMS-936558 (Nivolumab)
Drug: Dacarbazine
label
Dacarbazine, 1000 mg/m^2
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Nivolumab, 3 mg/kg
name
BMS-936558 (Nivolumab)
type
BIOLOGICAL
arm Group Labels
Dacarbazine, 1000 mg/m^2
name
Placebo matching BMS-936558 (Nivolumab)
type
BIOLOGICAL
arm Group Labels
Dacarbazine, 1000 mg/m^2
name
Dacarbazine
type
DRUG
arm Group Labels
Nivolumab, 3 mg/kg
name
Placebo matching Dacarbazine
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 418
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
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 up to 17 months.
description
OS rate is calculated as the percentage of participants alive at the indicated timepoints
measure
Overall Survival (OS) Rate
time Frame
From randomization to 6 months and or to 12 months

secondary Outcomes

description
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.
measure
Progression-free Survival (PFS)
time Frame
From date of randomization up to date of disease progression or death, up to approximately 84 months
description
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.
measure
Progression-free Survival (PFS) Rate
time Frame
From randomization to the specified timepoints, up to 84 months
description
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.
measure
Objective Response Rate (ORR)
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 94 months
description
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.
measure
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, up to approximately 94 months
description
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.
measure
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 93 months

Full study description

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

Source references

references

citation
Long GV, Larkin J, Schadendorf D, Grob JJ, Lao CD, Marquez-Rodas I, Wagstaff J, Lebbe C, Pigozzo J, Robert C, Ascierto PA, Atkinson V, Postow MA, Atkins MB, Sznol M, Callahan MK, Topalian SL, Sosman JA, Kotapati S, Thakkar PK, Ritchings C, Pe Benito M, Re S, Soleymani S, Hodi FS. Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma. J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.
pmid
39504507
type
DERIVED
citation
Robert C, Long GV, Brady B, Dutriaux C, Di Giacomo AM, Mortier L, Rutkowski P, Hassel JC, McNeil CM, Kalinka EA, Lebbe C, Charles J, Hernberg MM, Savage KJ, Chiarion-Sileni V, Mihalcioiu C, Mauch C, Arance A, Cognetti F, Ny L, Schmidt H, Schadendorf D, Gogas H, Zoco J, Re S, Ascierto PA, Atkinson V. Five-Year Outcomes With Nivolumab in Patients With Wild-Type BRAF Advanced Melanoma. J Clin Oncol. 2020 Nov 20;38(33):3937-3946. doi: 10.1200/JCO.20.00995. Epub 2020 Sep 30.
pmid
32997575
type
DERIVED
citation
Ascierto PA, Long GV, Robert C, Brady B, Dutriaux C, Di Giacomo AM, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbe C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Ny L, Arance A, Svane IM, Schadendorf D, Gogas H, Saci A, Jiang J, Rizzo J, Atkinson V. Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial. JAMA Oncol. 2019 Feb 1;5(2):187-194. doi: 10.1001/jamaoncol.2018.4514.
pmid
30422243
type
DERIVED
citation
Long GV, Tykodi SS, Schneider JG, Garbe C, Gravis G, Rashford M, Agrawal S, Grigoryeva E, Bello A, Roy A, Rollin L, Zhao X. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018 Nov 1;29(11):2208-2213. doi: 10.1093/annonc/mdy408.
pmid
30215677
type
DERIVED
citation
Long GV, Weber JS, Larkin J, Atkinson V, Grob JJ, Schadendorf D, Dummer R, Robert C, Marquez-Rodas I, McNeil C, Schmidt H, Briscoe K, Baurain JF, Hodi FS, Wolchok JD. Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials. JAMA Oncol. 2017 Nov 1;3(11):1511-1519. doi: 10.1001/jamaoncol.2017.1588.
pmid
28662232
type
DERIVED
citation
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, Lebbe 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.
pmid
25399552
type
DERIVED