Clinical trial NCT03036098: Study of Nivolumab in Combination With Ipilimumab or Standard of Care Chemotherapy Compared to the Standard of Care Chemotherapy Alone in Treatment of Participants With Untreated Inoperable or Metastatic Urothelial Cancer
Official title: A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab, or With Standard of Care Chemotherapy, Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Urothelial Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2017-01-30
Enrollment: 1322
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether an investigational immunotherapy nivolumab in combination with ipilimumab or in combination with standard of care chemotherapy is more effective than standard of care chemotherapy alone in treating participants with previously untreated inoperable or metastatic urothelial cancer.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological evidence of metastatic or surgically inoperable transitional cell cancer (TCC) of the urothelium involving the renal pelvis, ureter, bladder or urethra
* No prior systemic chemotherapy for metastatic or surgically inoperable urothelial cancer (UC)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Women and men must agree to follow specific methods of contraception, if applicable

Exclusion Criteria:

* Disease that is suitable for local therapy administered with curative intent
* Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results
* Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Overall survival (OS) in cisplatin-ineligible randomized participants
timeFrame: Up to 55 months
measure: Overall survival (OS) in PD-L1 positive (>=1%) randomized participants by immunohistochemistry (IHC)
timeFrame: Up to 52 months
measure: Progression-free survival (PFS) by blinded independent central review (BICR) (using RECIST 1.1) in cisplatin-eligible participants with previously untreated, unresectable or metastatic UC
timeFrame: Up to 64 months
measure: Overall survival (OS) in cisplatin-eligible participants with previously untreated, unresectable or metastatic UC
timeFrame: Up to 64 months
Secondary outcomes:
measure: Overall survival (OS) in all randomized participants
timeFrame: Up to 55 months
measure: Progression-free survival (PFS) by blinded independent central review (BICR) (using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in cisplatin-ineligible randomized participants
timeFrame: Up to 55 months
measure: Progression-free survival (PFS) by blinded independent central review (BICR) (using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in PD-L1 positive (≥1%) randomized participants
timeFrame: Up to 55 months
measure: Progression-free survival (PFS) by blinded independent central review (BICR) (using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in all randomized participants
timeFrame: Up to 55 months
measure: European Organisation for Research and Treatment of Care (EORTC) QLQ-C30 Global Health Status score in all randomized participants
timeFrame: Up to 55 months
measure: European Organisation for Research and Treatment of Care (EORTC) QLQ-C30 Global Health Status score in cisplatin eligible participants with previously untreated, unresectable or metastatic UC
timeFrame: Up to 64 months
measure: Progression-free survival (PFS) by BICR by PD-L1 expression at >=1% by immunohistochemistry (IHC)
timeFrame: Up to 64 months
measure: Overall survival (OS) by PD-L1 expression at ≥ 1% expression by immunohistochemistry (IHC)
timeFrame: Up to 64 months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Local Institution - 0001
state: Alaska
city: Fresno
country: United States
facility: Local Institution - 0115
state: California
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare
state: California
city: Boca Raton
country: United States
facility: Local Institution - 0051
state: Florida
city: Fort Lauderdale
country: United States
facility: Local Institution - 0087
state: Florida
city: Jacksonville
country: United States
facility: Local Institution - 0062
state: Florida
city: Athens
country: United States
facility: Local Institution - 0004
state: Georgia
city: Thomasville
country: United States
facility: Local Institution - 0033
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0046
state: Illinois
city: New Orleans
country: United States
facility: Local Institution - 0117
state: Louisiana
city: Boston
country: United States
facility: Local Institution - 0056
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0073
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0208
state: Massachusetts
city: Milford
country: United States
facility: Local Institution - 0207
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0063
state: Michigan
city: Burnsville
country: United States
facility: Local Institution - 0002
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Kansas City
country: United States
facility: Local Institution - 0032
state: Missouri
city: Saint Louis
country: United States
facility: Local Institution - 0095
state: Missouri
city: Manchester
country: United States
facility: Local Institution - 0057
state: New Hampshire
city: Albuquerque
country: United States
facility: Local Institution - 0084
state: New Mexico
city: Buffalo
country: United States
facility: Local Institution - 0083
state: New York
city: Mineola
country: United States
facility: Local Institution - 0014
state: New York
city: New York
country: United States
facility: Local Institution - 0072
state: New York
city: Durham
country: United States
facility: Local Institution - 0116
state: North Carolina
city: Columbus
country: United States
facility: Local Institution - 0082
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0104
state: Oregon
city: Pittsburgh
country: United States
facility: Local Institution - 0013
state: Pennsylvania
city: Kirkland
country: United States
facility: Local Institution - 0086
state: Washington
city: Capital Federal
country: Argentina
facility: Local Institution - 0005
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: Local Institution - 0007
state: Buenos Aires
city: Viedma
country: Argentina
facility: Local Institution - 0008
state: RIO Negro
city: Buenos Aires
country: Argentina
facility: Local Institution - 0009
city: Cordoba
country: Argentina
facility: Local Institution - 0134
city: Cordoba
country: Argentina
facility: Local Institution - 0006
city: Waratah
country: Australia
facility: Local Institution - 0096
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution - 0099
state: New South Wales
city: South Brisbane
country: Australia
facility: Local Institution - 0188
state: Queensland
city: Tugun
country: Australia
facility: Local Institution - 0120
state: Queensland
city: Heidelberg
country: Australia
facility: Local Institution - 0101
state: Victoria
city: Doubleview
country: Australia
facility: Local Institution - 0100
state: Western Australia
city: Brasilia
country: Brazil
facility: Local Institution - 0017
state: Distrito Federal
city: Ijui
country: Brazil
facility: Local Institution - 0021
state: RIO Grande DO SUL
city: Passo Fundo
country: Brazil
facility: Local Institution - 0119
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0020
state: RIO Grande DO SUL
city: Florianopolis
country: Brazil
facility: Local Institution - 0016
state: Santa Catarina
city: Barretos
country: Brazil
facility: Local Institution - 0018
state: Sao Paulo
city: Sao Jose Do Rio Preto
country: Brazil
facility: Local Institution - 0019
state: Sao Paulo
city: Halifax
country: Canada
facility: Local Institution - 0053
state: Nova Scotia
city: London
country: Canada
facility: Local Institution - 0064
state: Ontario
city: Quebec City
country: Canada
facility: Local Institution - 0054
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution - 0052
state: Quebec
city: Santiago
country: Chile
facility: Local Institution - 0010
state: Metropolitana
city: Vina del Mar
country: Chile
facility: Local Institution - 0012
state: Valparaiso
city: Vitacura
country: Chile
facility: Local Institution - 0106
city: Beijing
country: China
facility: Local Institution - 0171
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0169
state: Beijing
city: Chongqing
country: China
facility: Local Institution - 0182
state: Chongqing
city: Guiyang
country: China
facility: Local Institution - 0217
state: Guizhou
city: Harbin
country: China
facility: Local Institution - 0219
state: Heilongjiang
city: Wuhan
country: China
facility: Local Institution - 0180
state: Hubei
city: Nanjing
country: China
facility: Local Institution - 0177
state: Jiangsu
city: Nanjing
country: China
facility: Local Institution - 0176
state: Jiangsu
city: Nanjng
country: China
facility: Local Institution - 0175
state: Jiangsu
city: Changchun
country: China
facility: Local Institution - 0186
state: Jilin
city: Taiyuan
country: China
facility: Local Institution - 0220
state: Shan1xi
city: Yantai
country: China
facility: Local Institution - 0216
state: Shandong
city: Shanghai
country: China
facility: Local Institution - 0167
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0162
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0163
state: Shanghai
city: Chengdu
country: China
facility: Local Institution - 0184
state: Sichuan
city: Hangzhou
country: China
facility: Local Institution - 0173
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 0174
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution - 0172
state: Zhejiang
city: Beijing
country: China
facility: Local Institution - 0170
city: Shanghai
country: China
facility: Local Institution - 0164
city: Brno
country: Czechia
facility: Local Institution - 0160
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0152
city: Aalborg
country: Denmark
facility: Local Institution - 0190
city: Herlev
country: Denmark
facility: Local Institution - 0196
city: Helsinki
country: Finland
facility: Local Institution - 0060
city: Nîmes
country: France
facility: Local Institution - 0091
state: Gard
city: Lille
country: France
facility: Local Institution - 0089
city: Marseille Cedex 9
country: France
facility: Local Institution - 0088
city: St Priest En Jarez
country: France
facility: Local Institution - 0090
city: Suresnes
country: France
facility: Local Institution - 0092
city: Tours Cedex
country: France
facility: Local Institution - 0093
city: Villejuif
country: France
facility: Local Institution - 0094
city: Dresden
country: Germany
facility: Local Institution - 0036
city: Essen
country: Germany
facility: Local Institution - 0048
city: Freiburg
country: Germany
facility: Local Institution - 0047
city: Hamburg
country: Germany
facility: Local Institution - 0049
city: Hannover
country: Germany
facility: Local Institution - 0037
city: Jena
country: Germany
facility: Local Institution - 0041
city: Mannheim
country: Germany
facility: Local Institution - 0213
city: Nuernberg
country: Germany
facility: Local Institution - 0038
city: Tuebingen
country: Germany
facility: Local Institution - 0040
city: Weiden
country: Germany
facility: Local Institution - 0114
city: Wuerzburg
country: Germany
facility: Local Institution - 0039
city: Athens
country: Greece
facility: Local Institution - 0102
city: Ioannina
country: Greece
facility: Local Institution - 0103
state: Ípeiros
city: Kfar Saba
country: Israel
facility: Local Institution - 0199
city: Ramat Gan
country: Israel
facility: Local Institution - 0198
city: Arezzo
country: Italy
facility: Local Institution - 0108
city: Faenza
country: Italy
facility: Local Institution - 0197
city: Forlì
country: Italy
facility: Local Institution - 0111
city: Grosseto
country: Italy
facility: Local Institution - 0109
city: Milano
country: Italy
facility: Local Institution - 0107
city: Napoli
country: Italy
facility: Local Institution - 0110
city: Hirosaki
country: Japan
facility: Local Institution - 0136
state: Aomori
city: Chiba-shi
country: Japan
facility: Local Institution - 0135
state: Chiba
city: Matsuyama-shi
country: Japan
facility: Local Institution - 0147
state: Ehime
city: Fukuoka-shi
country: Japan
facility: Local Institution - 0140
state: Fukuoka
city: Sapporo-city
country: Japan
facility: Local Institution - 0146
state: Hokkaido
city: Tsukuba-shi
country: Japan
facility: Local Institution - 0150
state: Ibaraki
city: Morioka-shi
country: Japan
facility: Local Institution - 0214
state: Iwate
city: Kita-Gun
country: Japan
facility: Local Institution - 0137
state: Kagawa
city: Niigata-shi
country: Japan
facility: Local Institution - 0141
state: Niigata
city: Okayama-shi
country: Japan
facility: Local Institution - 0143
state: Okayama
city: Osaka-shi
country: Japan
facility: Local Institution - 0144
state: Osaka
city: Osakasayama
country: Japan
facility: Local Institution - 0139
state: Osaka
city: Takatsuki-shi
country: Japan
facility: Local Institution - 0145
state: Osaka
city: Hamamatasu
country: Japan
facility: Local Institution - 0201
state: Shizuoka
city: Adachi-ku
country: Japan
facility: Local Institution - 0149
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0148
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0142
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Local Institution - 0138
state: Tokyo
city: Wakayama-shi
country: Japan
facility: Local Institution - 0215
state: Wakayama
city: Ube City
country: Japan
facility: Local Institution - 0200
state: Yamaguchi
city: Goyang-si
country: Korea, Republic of
facility: Local Institution - 0125
state: Gyeonggido
city: Seongnam-si
country: Korea, Republic of
facility: Local Institution - 0126
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0124
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0151
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0128
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0127
city: Ciudad de Mexico
country: Mexico
facility: Local Institution - 0129
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Local Institution - 0154
state: Distrito Federal
city: Tlalpan
country: Mexico
facility: Local Institution - 0130
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Local Institution - 0131
state: Nuevo Leon
city: Amsterdam
country: Netherlands
facility: Local Institution - 0022
state: Noord-Holland
city: Enschede
country: Netherlands
facility: Local Institution - 0055
city: Groningen
country: Netherlands
facility: Local Institution - 0024
city: Leeuwarden
country: Netherlands
facility: Local Institution - 0026
city: Bergen
country: Norway
facility: Local Institution - 0074
city: Lorenskog
country: Norway
facility: Local Institution - 0081
city: Lima
country: Peru
facility: Local Institution - 0030
city: Lima
country: Peru
facility: Local Institution - 0031
city: Bydgoszcz
country: Poland
facility: Local Institution - 0189
city: Koszalin
country: Poland
facility: Local Institution - 0205
city: Warszawa
country: Poland
facility: Local Institution - 0202
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0191
state: Cluj
city: Craiova
country: Romania
facility: Local Institution - 0187
state: Dolj
city: Moscow
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution - 0192
state: Central Singapore
city: A Coruna
country: Spain
facility: Local Institution - 0070
city: Barcelona
country: Spain
facility: Local Institution - 0068
city: Madrid
country: Spain
facility: Local Institution - 0065
city: Madrid
country: Spain
facility: Local Institution - 0066
city: Santander
country: Spain
facility: Local Institution - 0209
city: Sevilla
country: Spain
facility: Local Institution - 0067
city: Valencia
country: Spain
facility: Local Institution - 0069
city: Jonkoping
country: Sweden
facility: Local Institution - 0075
city: Linkoping
country: Sweden
facility: Local Institution - 0059
city: Lund
country: Sweden
facility: Local Institution - 0058
city: Baden
country: Switzerland
facility: Local Institution - 0061
state: Aargau
city: Chur
country: Switzerland
facility: Local Institution - 0042
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0156
city: Taichung
country: Taiwan
facility: Local Institution - 0159
city: Taipei
country: Taiwan
facility: Local Institution - 0158
city: Taipei
country: Taiwan
facility: Local Institution - 0155
city: Taoyuan
country: Taiwan
facility: Local Institution - 0157
city: Ankara
country: Turkey
facility: Local Institution - 0194
city: Istanbul
country: Turkey
facility: Local Institution - 0204
city: Izmir
country: Turkey
facility: Local Institution - 0193
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: