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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04209114




Registration number
NCT04209114
Ethics application status
Date submitted
20/12/2019
Date registered
23/12/2019

Titles & IDs
Public title
A Study of Nivolumab Plus Bempegaldesleukin (Bempeg/NKTR-214) vs Nivolumab Alone vs Standard of Care in Participants With Bladder Cancer That May Have Invaded The Muscle Wall of the Bladder and Who Cannot Get Cisplatin, A Type of Medicine Given To Treat Bladder Cancer
Scientific title
A Phase 3, Randomized, Study of Neoadjuvant and Adjuvant Nivolumab Plus Bempegaldesleukin (NKTR-214), Versus Nivolumab Alone Versus Standard of Care in Participants With Muscle-Invasive Bladder Cancer (MIBC) Who Are Cisplatin Ineligible
Secondary ID [1] 0 0
2018-002676-40
Secondary ID [2] 0 0
CA045-009
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bladder Cancer 0 0
Bladder Tumor 0 0
Muscle-Invasive Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Nivolumab
Treatment: Surgery - Radical cystectomy (RC)
Treatment: Other - Bempegaldesleukin

Experimental: Arm A: Combination Therapy - Neoadjuvant (pre-surgical treatment) nivolumab + bempeg, followed by radical cystectomy (RC), followed by adjuvant (post-surgical treatment) nivolumab + bempeg

Experimental: Arm B: Monotherapy - Neoadjuvant nivolumab, followed by RC, followed by adjuvant nivolumab

Other: Arm C: Standard-of-care - RC alone, without neoadjuvant or adjuvant therapy


Treatment: Other: Nivolumab
Specified dose on specified days

Treatment: Surgery: Radical cystectomy (RC)
Surgical removal of the bladder

Treatment: Other: Bempegaldesleukin
Specified dose on specified days

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

Outcomes
Primary outcome [1] 0 0
Pathologic Complete Response (pCR) Rate- Nivolumab + Bempegaldesleukin Compared to Standard of Care
Timepoint [1] 0 0
From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months)
Primary outcome [2] 0 0
Event Free Survival (EFS) - Nivolumab + Bempegaldesleukin Compared to Standard of Care
Timepoint [2] 0 0
From randomization up to first EFS event (up to approximately 30 months)
Secondary outcome [1] 0 0
Pathologic Complete Response (pCR) Rate - Nivolumab Compared to Standard of Care
Timepoint [1] 0 0
From time of radical cystectomy up to 100 days after last treatment (up to approximately 17 months)
Secondary outcome [2] 0 0
Event Free Survival (EFS) - Nivolumab Compared to Standard of Care
Timepoint [2] 0 0
From randomization up to first EFS event (up to approximately 30 months)
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
From randomization to study completion, up to approximately 40 months
Secondary outcome [4] 0 0
The Number of Participants Experiencing Adverse Events (AEs)
Timepoint [4] 0 0
from first dose to 100 days following last dose (up to approximately 20 months)
Secondary outcome [5] 0 0
The Number of Participants Experiencing Serious Adverse Events (SAEs)
Timepoint [5] 0 0
from first dose to 100 days following last dose (up to approximately 20 months)
Secondary outcome [6] 0 0
The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Timepoint [6] 0 0
from first dose to 100 days following last dose (up to approximately 20 months)
Secondary outcome [7] 0 0
The Number of Participants Experiencing Immune-Mediated Adverse Events (IMAEs)
Timepoint [7] 0 0
from first dose to 100 days following last dose (up to approximately 20 months)
Secondary outcome [8] 0 0
Worst Grade Clinical Laboratory Values
Timepoint [8] 0 0
From first dose to 100 days following last dose (up to approximately 20 months)

Eligibility
Key inclusion criteria
* Urothelial carcinoma (UC) of the bladder, clinical stage T2-T4aN0, M0 or T1-T4aN1, M0, diagnosed at transurethral resection of bladder tumor (TURBT)
* Must be deemed eligible for Radical Cystectomy (RC) by urologist, and must agree to undergo RC. For arms A and B, participants must agree to undergo RC after completion of neoadjuvant therapy.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Cisplatin-ineligible participants will be defined by any one of the following criteria:

i) Impaired renal function (glomerular filtration rate [GFR] = 30 but < 60 mL/min) ii) GFR should be assessed by direct measurement (ie, creatinine clearance) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula) iii) Common Terminology Criteria for Adverse Events (CTCAE) version 5, = Grade 2 hearing loss (assessed per local SOC).

iv) CTCAE version 5, = Grade 2 peripheral neuropathy.

* Documented Left Ventricular Ejection Fraction (LVEF) more than 45%
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Clinical evidence of = N2 or metastatic bladder cancer
* Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies is not permitted. Prior Bacillus Calmette-Guerin (BCG) or other intravesicular treatment of non-muscle invasive bladder cancer (NMIBC) is permitted if completed at least 6 weeks prior to initiating study treatment.
* Evidence of urothelial carcinoma (UC) in upper urinary tracts (ureters or renal pelvis) or history of previous MIBC
* History of pulmonary embolism (PE), deep vein thrombosis (DVT), or prior clinically significant venous or non-CVA(cerebrovascular accident)/TIA (Transient ischemic attack) arterial thromboembolic event
* Known cardiovascular history, including unstable or deteriorating cardiac disease within the previous 12 months (including unstable angina or myocardial infarction, congestive heart failure or uncontrolled clinically significant arrhythmias)

Other protocol-defined inclusion/exclusion criteria apply

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
Completed
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,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - 0137 - Gosford
Recruitment hospital [2] 0 0
Local Institution - 0158 - Ballarat
Recruitment hospital [3] 0 0
Local Institution - 0157 - Fitzroy
Recruitment hospital [4] 0 0
Local Institution - 0011 - Heidelberg
Recruitment hospital [5] 0 0
Local Institution - 0013 - Murdoch
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
3350 - Ballarat
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
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
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Argentina
State/province [12] 0 0
Distrito Federal
Country [13] 0 0
Argentina
State/province [13] 0 0
Santa FE
Country [14] 0 0
Argentina
State/province [14] 0 0
Cordoba
Country [15] 0 0
Austria
State/province [15] 0 0
Graz
Country [16] 0 0
Austria
State/province [16] 0 0
Vienna
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
Antwerpen
Country [19] 0 0
Belgium
State/province [19] 0 0
Brussels
Country [20] 0 0
Belgium
State/province [20] 0 0
Edegem
Country [21] 0 0
Belgium
State/province [21] 0 0
Gent
Country [22] 0 0
Belgium
State/province [22] 0 0
Liège
Country [23] 0 0
Brazil
State/province [23] 0 0
RIO Grande DO SUL
Country [24] 0 0
Brazil
State/province [24] 0 0
SAO Paulo
Country [25] 0 0
Brazil
State/province [25] 0 0
Sao Paulo
Country [26] 0 0
Brazil
State/province [26] 0 0
São Paulo
Country [27] 0 0
Brazil
State/province [27] 0 0
Rio de Janeiro
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
China
State/province [30] 0 0
Chongqing
Country [31] 0 0
China
State/province [31] 0 0
Fujian
Country [32] 0 0
China
State/province [32] 0 0
Henan
Country [33] 0 0
China
State/province [33] 0 0
Hubei
Country [34] 0 0
China
State/province [34] 0 0
Hunan
Country [35] 0 0
China
State/province [35] 0 0
Shan1xi
Country [36] 0 0
China
State/province [36] 0 0
Shandong
Country [37] 0 0
Czechia
State/province [37] 0 0
Olomouc
Country [38] 0 0
Czechia
State/province [38] 0 0
Praha 5
Country [39] 0 0
Czechia
State/province [39] 0 0
Praha
Country [40] 0 0
France
State/province [40] 0 0
Avignon Cedex 9
Country [41] 0 0
France
State/province [41] 0 0
Bordeaux
Country [42] 0 0
France
State/province [42] 0 0
Clermont-Ferrand
Country [43] 0 0
France
State/province [43] 0 0
La Roche-sur-Yon
Country [44] 0 0
France
State/province [44] 0 0
Lyon
Country [45] 0 0
France
State/province [45] 0 0
Marseille Cedex 9
Country [46] 0 0
France
State/province [46] 0 0
Montpellier
Country [47] 0 0
France
State/province [47] 0 0
Nice
Country [48] 0 0
France
State/province [48] 0 0
Paris
Country [49] 0 0
France
State/province [49] 0 0
Quimper
Country [50] 0 0
France
State/province [50] 0 0
Reims
Country [51] 0 0
France
State/province [51] 0 0
Strasbourg
Country [52] 0 0
France
State/province [52] 0 0
Suresnes
Country [53] 0 0
France
State/province [53] 0 0
Tours
Country [54] 0 0
Germany
State/province [54] 0 0
Dresden
Country [55] 0 0
Germany
State/province [55] 0 0
Duesseldorf
Country [56] 0 0
Germany
State/province [56] 0 0
Erlangen
Country [57] 0 0
Germany
State/province [57] 0 0
Essen
Country [58] 0 0
Germany
State/province [58] 0 0
Hamburg
Country [59] 0 0
Germany
State/province [59] 0 0
Herne
Country [60] 0 0
Germany
State/province [60] 0 0
Jena
Country [61] 0 0
Germany
State/province [61] 0 0
Luebeck
Country [62] 0 0
Germany
State/province [62] 0 0
Muenster
Country [63] 0 0
Germany
State/province [63] 0 0
Nuernberg
Country [64] 0 0
Germany
State/province [64] 0 0
Tuebingen
Country [65] 0 0
Greece
State/province [65] 0 0
Athens
Country [66] 0 0
Greece
State/province [66] 0 0
Chaidari
Country [67] 0 0
Greece
State/province [67] 0 0
Thessaloniki
Country [68] 0 0
Israel
State/province [68] 0 0
Haifa
Country [69] 0 0
Israel
State/province [69] 0 0
Tel Aviv
Country [70] 0 0
Israel
State/province [70] 0 0
Tel Hashomer
Country [71] 0 0
Italy
State/province [71] 0 0
Firenze
Country [72] 0 0
Italy
State/province [72] 0 0
Milano
Country [73] 0 0
Italy
State/province [73] 0 0
Pavia
Country [74] 0 0
Italy
State/province [74] 0 0
Pisa
Country [75] 0 0
Italy
State/province [75] 0 0
Roma
Country [76] 0 0
Italy
State/province [76] 0 0
Rozzano
Country [77] 0 0
Mexico
State/province [77] 0 0
BAJA Californa SUR
Country [78] 0 0
Mexico
State/province [78] 0 0
Distrito Federal
Country [79] 0 0
Mexico
State/province [79] 0 0
Nuevo LEON
Country [80] 0 0
Netherlands
State/province [80] 0 0
Amsterdam
Country [81] 0 0
Poland
State/province [81] 0 0
Biala Podlaska
Country [82] 0 0
Poland
State/province [82] 0 0
Warszawa
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Omsk
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Saint-Petersburg
Country [85] 0 0
Spain
State/province [85] 0 0
A Coruña
Country [86] 0 0
Spain
State/province [86] 0 0
Badalona
Country [87] 0 0
Spain
State/province [87] 0 0
Barcelona
Country [88] 0 0
Spain
State/province [88] 0 0
Cordoba
Country [89] 0 0
Spain
State/province [89] 0 0
Madrid
Country [90] 0 0
Spain
State/province [90] 0 0
Santander
Country [91] 0 0
Spain
State/province [91] 0 0
Sevilla
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Hertfordshire
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Leicester
Country [94] 0 0
United Kingdom
State/province [94] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Nektar Therapeutics
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual patient level data from this study may be shared with qualified researchers, upon request, following the timelines and process detailed on https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.