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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01642004




Registration number
NCT01642004
Ethics application status
Date submitted
9/07/2012
Date registered
17/07/2012
Date last updated
26/06/2020

Titles & IDs
Public title
Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017)
Scientific title
An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC)
Secondary ID [1] 0 0
2011-004792-36
Secondary ID [2] 0 0
CA209-017
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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.

Experimental: 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 196 deaths, with the actual analysis occurring at 199 deaths.
Timepoint [1] 0 0
Randomization until 199 deaths, up to November 2014, approximately 25 months
Primary outcome [2] 0 0
Overall Survival (OS) Rate in All Randomized Participants - The overall survival rate is the probability that a participant will be alive at 6, 12, and 18 months following randomization. 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
Randomization to 18 months post-randomization, up to June 2015
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 196 deaths, with the actual analysis occurring at 199 deaths.
Timepoint [3] 0 0
Randomization until 199 deaths, up to November 2014, approximately 25 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint - 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). 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 199 deaths, up to November 2014, approximately 25 months
Secondary outcome [2] 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 [2] 0 0
Randomization until confirmed response, up to November 2014, approximately 25 months
Secondary outcome [3] 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 [3] 0 0
Date of confirmed response to date of documented tumor progression, up to November 2014, approximately 25 months
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) at Primary Endpoint - PFS rate was defined as the probability that participants will experience no disease progression or death from any cause at a given time point following randomization. Progression was assessed by investigators according to RECIST v1.1. 95% CIs were estimated using the Kaplan-Meier method. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative radiation therapy (RT) of non-target bone lesions or CNS lesions) without a prior reported progression were to be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy
Timepoint [4] 0 0
Randomization to 12 months post-randomization, up to November 2014
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% CI for median PFS were computed by Brookmeyer and Crowley method (using log-log transformation). Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative RT of non-target bone lesions or CNS lesions) without a prior reported progression were to be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy.
Timepoint [5] 0 0
Randomization until 199 deaths, up to November 2014, approximately 25 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 - OS was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. 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. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
Timepoint [7] 0 0
Randomization until 199 deaths, up to November 2014, approximately 25 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. 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). 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. 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 199 deaths, up to November 2014, approximately 25 months
Secondary outcome [9] 0 0
Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint - PFS time was measured for all randomized participants grouped by their baseline PD-L1 expression levels. 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. The PFS curves were estimated using KM method. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started subsequent anti-cancer therapy (including on-treatment palliative radiotherapy of non-target bone lesions or CNS lesions) without a prior reported progression were censored at the last evaluable tumor assessment prior to subsequent anti-cancer therapy. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
Timepoint [9] 0 0
Randomization until 199 deaths, up to November 2014, approximately 25 months

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



- Men and women =18 years of age

- Subjects with histologically or cytologically-documented squamous cell NSCLC who
present with Stage IIIB/IV disease or with recurrent or progressive disease following
multimodal therapy (radiation therapy, surgical resection or definitive chemoradiation
therapy for locally 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
Response Evaluation Criteria in Solid Tumors (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 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 =10 mg daily
prednisone (or equivalent)

- Subjects with carcinomatous meningitis

- Subjects with active, known or suspected autoimmune disease. Subjects with type I
diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders
(such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger 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 (PD-1), anti-Programmed cell death ligand 1
(PD-L1), anti-Programmed cell death ligand 2 (PD-L2), anti-CD137, or anti-Cytotoxic T
lymphocyte-associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other
antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)

- Prior treatment on the first line study CA184104 first line NSCLC study

- Prior treatment with Docetaxel

- Subjects with interstitial lung disease that is symptomatic or may interfere with the
detection or management of suspected drug-related pulmonary toxicity

- 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,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - Wollongong
Recruitment hospital [2] 0 0
Local Institution - Adelaide
Recruitment hospital [3] 0 0
Local Institution - Elizabeth Vale
Recruitment hospital [4] 0 0
Local Institution - Kurralta Park
Recruitment hospital [5] 0 0
Local Institution - Clayton
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
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United States of America
State/province [4] 0 0
Florida
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Georgia
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Illinois
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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New York
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North Carolina
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Ohio
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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United States of America
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Washington
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United States of America
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West Virginia
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Argentina
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Buenos Aires
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Argentina
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Tucuman
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Argentina
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Cordoba
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Austria
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Linz
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Austria
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Salzburg
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Austria
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Vienna
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Austria
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Wels
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Canada
State/province [25] 0 0
Manitoba
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Canada
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Quebec
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Chile
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Metropolitana
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Chile
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Santiago DE Chile
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Chile
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Valparaiso
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Chile
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Antofagasta
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Chile
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Santiago
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Czechia
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Praha 8
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France
State/province [33] 0 0
Avignon Cedes 9
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France
State/province [34] 0 0
Caen
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France
State/province [35] 0 0
Dijon
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France
State/province [36] 0 0
La Roche Sur Yon Cedex 9
Country [37] 0 0
France
State/province [37] 0 0
Lyon Cedex 08
Country [38] 0 0
France
State/province [38] 0 0
Marseille Cedex 20
Country [39] 0 0
France
State/province [39] 0 0
Pierre Benite
Country [40] 0 0
France
State/province [40] 0 0
Rennes Cedex 9
Country [41] 0 0
France
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Strasbourg
Country [42] 0 0
France
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Toulouse
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Germany
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Bad Berka
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Germany
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Essen
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Germany
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Gerlingen
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Germany
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Grosshansdorf
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Germany
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Heidelberg
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Germany
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Koeln
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Germany
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Krefeld
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Hungary
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Budapest
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Ireland
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Dublin
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Italy
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Bologna
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Italy
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Meldola (fc)
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Italy
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Milano
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Italy
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Padova
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Italy
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Perugia
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Italy
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Ravenna
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Italy
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Siena
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Mexico
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Distrito Federal
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Mexico
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Guanajuato
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Mexico
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Sonora
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Netherlands
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Amsterdam
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Netherlands
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Rotterdam
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Peru
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Arequipa
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Peru
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Lima
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Poland
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Gdansk
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Poland
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Krakow
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Poland
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Olsztyn
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Poland
State/province [69] 0 0
Szczecin
Country [70] 0 0
Poland
State/province [70] 0 0
Warszawa
Country [71] 0 0
Romania
State/province [71] 0 0
Bucuresti
Country [72] 0 0
Romania
State/province [72] 0 0
Cluj-Napoca
Country [73] 0 0
Romania
State/province [73] 0 0
Constanta
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Romania
State/province [74] 0 0
Craiova
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Romania
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Iasi
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Romania
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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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Spain
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Vizcaya
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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
State/province [82] 0 0
Sevilla
Country [83] 0 0
United Kingdom
State/province [83] 0 0
EAST Yorkshire
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Hampshire
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Manchester
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Yorkshire

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 as compared with
Docetaxel in subjects with squamous cell non-small cell lung cancer (NSCLC), after failure of
prior platinum-based chemotherapy.
Trial website
https://clinicaltrials.gov/show/NCT01642004
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