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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
Date last updated
27/06/2024

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
5/02/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/06/2023
Sample size
Target
Accrual to date
Final
114
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
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Arizona
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California
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Iowa
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Minnesota
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New York
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Pennsylvania
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South Carolina
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Texas
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Washington
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Argentina
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Buenos Aires
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Argentina
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Distrito Federal
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Argentina
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Santa FE
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Argentina
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Cordoba
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Austria
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Graz
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Austria
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Vienna
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Austria
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Wien
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Belgium
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Antwerpen
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Belgium
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Brussels
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Belgium
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Edegem
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Belgium
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Gent
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Belgium
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Liège
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Brazil
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RIO Grande DO SUL
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Brazil
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SAO Paulo
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Brazil
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Sao Paulo
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São Paulo
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Brazil
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Quebec
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China
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Chongqing
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Fujian
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China
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Henan
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China
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Hubei
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China
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Hunan
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Shan1xi
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China
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Shandong
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Czechia
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Olomouc
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Czechia
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Praha 5
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Czechia
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Praha
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Avignon Cedex 9
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Bordeaux
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Clermont-Ferrand
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La Roche-sur-Yon
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Lyon
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Marseille Cedex 9
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France
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Montpellier
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France
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Nice
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France
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Paris
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France
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Quimper
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France
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Reims
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France
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France
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Suresnes
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France
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Tours
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Dresden
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Duesseldorf
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Erlangen
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Germany
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Essen
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Hamburg
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Germany
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Herne
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Germany
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Jena
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Germany
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Luebeck
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Germany
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Muenster
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Germany
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Nuernberg
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Germany
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Tuebingen
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Greece
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Athens
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Greece
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Chaidari
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Greece
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Thessaloniki
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Israel
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Haifa
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Israel
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Tel Aviv
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Israel
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Tel Hashomer
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Italy
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Firenze
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Italy
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Milano
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Italy
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Pavia
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Italy
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Pisa
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Italy
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Roma
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Italy
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Rozzano
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Mexico
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BAJA Californa SUR
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Mexico
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Distrito Federal
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Mexico
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Nuevo LEON
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Netherlands
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Amsterdam
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Poland
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Biala Podlaska
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Poland
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Warszawa
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Russian Federation
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Omsk
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Russian Federation
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Saint-Petersburg
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Spain
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A Coruña
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Cordoba
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Spain
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Madrid
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Spain
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Santander
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Spain
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Sevilla
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United Kingdom
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Hertfordshire
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United Kingdom
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Leicester
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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
The purpose of the study is to see if treatment with nivolumab plus bempegaldesleukin or nivolumab alone, before and after surgery to remove the bladder, is more effective than surgery alone in participants with high-risk urothelial cancer, including muscle-invasive bladder cancer who are not able to receive cisplatin chemotherapy.
Trial website
https://clinicaltrials.gov/study/NCT04209114
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04209114