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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01673867




Registration number
NCT01673867
Ethics application status
Date submitted
24/08/2012
Date registered
28/08/2012
Date last updated
23/06/2020

Titles & IDs
Public title
Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC
Scientific title
An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)
Secondary ID [1] 0 0
2012-002472-14
Secondary ID [2] 0 0
CA209-057
Universal Trial Number (UTN)
Trial acronym
CheckMate057
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Squamous Cell Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Nivolumab
Treatment: Drugs - Docetaxel

Experimental: Arm A: Nivolumab - Nivolumab 3 mg/kg solution intravenously (IV) every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.

Active Comparator: Arm B: Docetaxel - Docetaxel 75 mg/m^2 concentrate for solution for intravenous infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends. Eligible patients may receive nivolumab at 480mg every 4 weeks until documented disease progression, discontinuation, withdrawal of consent or the study ends.


Other interventions: Nivolumab


Treatment: Drugs: Docetaxel


Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint - OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
Timepoint [1] 0 0
Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Primary outcome [2] 0 0
One-year Overall Survival (OS) Rate in All Randomized Participants - The one-year overall survival rate is a percentage, representing the fraction of all randomized participants who were alive following one year of treatment. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.
Timepoint [2] 0 0
12 months
Primary outcome [3] 0 0
Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint - The number of participants who died from any cause was reported for each arm. Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
Timepoint [3] 0 0
Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint - ORR was defined as the percentage of participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). BOR was defined as the best investigator-assessed response designation, recorded between the date of randomization and the date of objectively documented progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or the date of subsequent anti-cancer therapy (excluding on-treatment palliative radiotherapy of non-target bone lesions or Central Nervous System (CNS) lesions), whichever occurred first.
CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CIs were computed using the Clopper and Pearson method.
Timepoint [1] 0 0
Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Secondary outcome [2] 0 0
Duration of Objective Response (DOR) in Months for All Confirmed Responders at Primary Endpoint - DOR was defined as the time from the date of first confirmed response to the date of the first documented tumor progression (per RECIST v1.1), as determined by the investigator, or death due to any cause, whichever occurred first. DOR was evaluated only for confirmed responders (i.e. participants with confirmed CR or PR).
CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters.
Participants who neither progressed nor died were censored on the date of their last evaluable tumor assessment.
Timepoint [2] 0 0
Date of confirmed response to date of documented tumor progression or death, up to March 2015 (approximately 29 months)
Secondary outcome [3] 0 0
Time To Response (TTR) in Months for All Confirmed Responders at Primary Endpoint - Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters.
Timepoint [3] 0 0
Randomization until confirmed response, up to March 2015 (approximately 29 months)
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) Rate at 12 Months - PFS rate was defined as the percentage of participants experiencing no disease progression or death from any cause at 12 months after randomization. Progression was assessed by investigators according to RECIST v1.1. 95% CIs were estimated using the Kaplan-Meier method.
Timepoint [4] 0 0
Randomization to 12 months
Secondary outcome [5] 0 0
Progression-Free Survival (PFS) Time in Months for All Randomized Participants at Primary Endpoint - PFS was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator per RECIST v1.1 criteria, or death due to any cause. Participants underwent radiographic tumor assessments every 6 weeks (+/- 5 days) from week 9 (+/- 5 days) for the first year on treatment, then every 12 weeks after the first year on treatment until documented disease progression. The PFS curves were estimated using KM method. Two-sided 95% CIs for median PFS were computed by Brookmeyer and Crowley method (using log-log transformation). Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
Timepoint [5] 0 0
Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Secondary outcome [6] 0 0
Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12 - Disease-related symptom improvement rate by Week 12 was defined as the percentage of randomized participants who had a 10 point or greater decrease from baseline in average symptom burden index score at any time between randomization and Week 12. The participant portion of the Lung Cancer Symptom Scale (LCSS) consisted of 6 symptom-specific questions that addressed cough, dyspnea, fatigue, pain, hemoptysis, and anorexia, plus 3 summary items on symptom distress, interference with activity level, and global health-related Quality of Life (QoL). The scores range from 0 to 100, with 0 representing the best possible score and 100 being the worst possible score. The average symptom burden index score at each assessment was defined as the mean of the 6 symptom-specific questions of the LCSS. 95% CIs were computed using Clopper-Pearson Method.
Timepoint [6] 0 0
Randomization to Week 12
Secondary outcome [7] 0 0
Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint - Overall Survival time was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
Timepoint [7] 0 0
Randomization until 413 deaths, up to March 2015 (approximately 29 months)
Secondary outcome [8] 0 0
Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint - ORR was reported for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CIs were computed using the Clopper and Pearson method.
Timepoint [8] 0 0
Randomization until 413 deaths, up to March 2015 (approximately 29 months)

Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com



- Men & women =18 years of age

- Subjects with histologically or cytologically-documented non-squamous cell NSCLC who
present with Stage IIIB/IV disease or recurrent or progressive disease following
multimodal therapy (radiation therapy, surgical resection, or definitive
chemoradiation therapy for locally advanced disease) and who will receive study
therapy as second or third line of treatment for advanced disease

- Disease recurrence or progression during/after one prior platinum doublet-based
chemotherapy regimen for advanced or metastatic disease

- Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per
RECIST 1.1 criteria

- Eastern Cooperative Oncology Group (ECOG) performance status =1

- A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of
tumor sample (archival or recent) must be available for biomarker evaluation.
Specimens must be received by the central lab prior to randomization. Biopsy should be
excisional, incisional or core needle. Fine needle aspiration is insufficient
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects
are eligible if CNS metastases are asymptomatic or treated and subjects are
neurologically returned to baseline for at least 2 weeks prior to enrollment. In
addition, subjects must be either off corticosteroids, or on a stable or decreasing
dose of =10mg daily prednisone (or equivalent)

- Subjects with carcinomatous meningitis

- Subjects with active or recent history of known or suspected autoimmune disease.
Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone
replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring
systemic treatment are permitted to enroll

- Subjects with a condition requiring systemic treatment with either corticosteroids or
other immunosuppressive medications within 14 days of randomization

- Prior therapy with anti-programmed death-1 (anti-PD-1), anti-programmed cell death
ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-cluster
of differentiation 137 (anti-CD137), or anti-Cytotoxic T lymphocyte-associated antigen
4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint pathways)

- Prior treatment with Docetaxel

- Treatment with any investigational agent within 14 days of first administration of
study treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - Tweed Heads
Recruitment hospital [2] 0 0
Local Institution - Woolloongabba
Recruitment hospital [3] 0 0
Local Institution - Adelaide
Recruitment hospital [4] 0 0
Local Institution - Kurralta Park
Recruitment hospital [5] 0 0
Local Institution - Frankston
Recruitment hospital [6] 0 0
Local Institution - Melbourne
Recruitment postcode(s) [1] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment postcode(s) [6] 0 0
3065 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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Connecticut
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Florida
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Georgia
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Illinois
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Maryland
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Massachusetts
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New Hampshire
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New York
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North Carolina
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Texas
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Washington
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Argentina
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La Rioja
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Linz
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Salzburg
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Vienna
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Wels
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Bahia
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Ceara
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SAO Paulo
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Praha 8
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Creteil
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La Roche Sur Yon Cedex 9
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Lyon Cedex 08
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Marseille Cedex 20
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Poitiers
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Bologna
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Siena
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Distrito Federal
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Mexico
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Nuevo LEON
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Sonora
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Norway
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Oslo
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Peru
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Lima
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Peru
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Arequipa
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Poland
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Gdansk
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Krakow
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Olsztyn
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Szczecin
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Poland
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Warszawa
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Romania
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Bucuresti
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Romania
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Cluj-Napoca
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Craiova
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Iasi
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Timisoara
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Russian Federation
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Moscow
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Russian Federation
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St. Petersburg
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Sevilla
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Spain
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Vizcaya
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Switzerland
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Basel
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Switzerland
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Chur

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the study is to compare the overall survival of BMS-936558 (Nivolumab) as
compared with Docetaxel in subjects with non-squamous cell non-small cell lung cancer (NSCLC)
after failure of prior platinum-based chemotherapy
Trial website
https://clinicaltrials.gov/show/NCT01673867
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications