Clinical trial NCT03143153: A Study to Evaluate Efficacy in Subjects With Esophageal Cancer Treated With Nivolumab and Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin
Official title: A Randomized Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin in Subjects With Unresectable Advanced, Recurrent or Metastatic Previously Untreated Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Various Advanced Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2017-05-08
Enrollment: 970
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 main purpose of this study is to compare how long subjects with esophageal cancer live overall or live without disease progression after receiving nivolumab and ipilimumab or nivolumab combined with fluorouracil plus cisplatin versus fluorouracil plus cisplatin


Eligibility criteria: Inclusion Criteria:

* Must have histologically confirmed squamous cell carcinoma or adenosquamous cell carcinoma of esophagus
* Male or Female at least 18 years of age
* Must have esophageal cancer that cannot be operated on, or treated with definitive chemoradiation with curative intent, that is advanced, reoccurring or has spread out
* Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work
* Must agree to provide tumor tissue sample, either from a previous surgery or biopsy within 6 months or fresh, prior to the start of treatment in this study

Exclusion Criteria

* Presence of tumor cells in the brain or spinal cord which are symptomatic or require treatment
* Active known or suspected autoimmune disease
* Any serious or uncontrolled medical disorder or active infection
* Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
* Any positive test result for hepatitis B or C indicating acute or chronic infection and/or detectable virus

Other protocol defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Overall Survival (OS) in Participants With Tumor Cell PD-L1
timeFrame: From the date of randomization to up to the date of death (up to approximately 20 months)
measure: Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1
timeFrame: From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 9 months)
Secondary outcomes:
measure: Overall Survival (OS) in All Randomized Participants
timeFrame: From the date of randomization to up to the date of death (up to approximately 16 months)
measure: Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR
timeFrame: From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 7 months)
measure: Objective Response Rate (ORR) as Assessed by BICR
timeFrame: From the date of randomization to up to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to 40 months)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Local Institution - 0191
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: Usc/Norris Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: Local Institution - 0188
state: Colorado
city: Miami
country: United States
facility: University Of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Local Institution - 0186
state: Florida
city: Tampa
country: United States
facility: Local Institution - 0225
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0074
state: Georgia
city: Marietta
country: United States
facility: Local Institution - 0032
state: Georgia
city: Neptune
country: United States
facility: Hackensack Meridian Jersey Shore University Medical Center
state: New Jersey
city: Eugene
country: United States
facility: Oncology Associates Of Oregon, Pc
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Dallas
country: United States
facility: Local Institution - 0210
state: Texas
city: Houston
country: United States
facility: Local Institution - 0028
state: Texas
city: Roanoke
country: United States
facility: Local Institution - 0190
state: Virginia
city: Morgantown
country: United States
facility: Local Institution - 0203
state: West Virginia
city: Capital Federal
country: Argentina
facility: Local Institution - 0050
state: Buenos Aires
city: Rosario
country: Argentina
facility: Local Institution - 0086
state: Santa FE
city: Buenos Aires
country: Argentina
facility: Local Institution - 0048
city: La Rioja
country: Argentina
facility: Local Institution - 0087
city: Tamworth
country: Australia
facility: Local Institution - 0232
state: New South Wales
city: Douglas
country: Australia
facility: Local Institution - 0011
state: Queensland
city: Murdoch
country: Australia
facility: Local Institution - 0010
state: Western Australia
city: Salzburg
country: Austria
facility: Local Institution - 0241
city: Salvador
country: Brazil
facility: Local Institution - 0017
state: Bahia
city: Ipatinga
country: Brazil
facility: Local Institution - 0227
state: Minas Gerais
city: Ijui
country: Brazil
facility: Local Institution - 0021
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0016
state: RIO Grande DO SUL
city: Barretos
country: Brazil
facility: Local Institution - 0019
state: Sao Paulo
city: Jau
country: Brazil
facility: Local Institution - 0226
state: Sao Paulo
city: São José do Rio Preto
country: Brazil
facility: Local Institution - 0018
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0228
city: Sao Paulo
country: Brazil
facility: Local Institution - 0020
city: Moncton
country: Canada
facility: Local Institution - 0095
state: New Brunswick
city: Montreal
country: Canada
facility: Local Institution - 0082
state: Quebec
city: Montreal
country: Canada
facility: Local Institution - 0222
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Local Institution - 0037
state: Quebec
city: Santiago
country: Chile
facility: Local Institution - 0053
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0214
state: Metropolitana
city: Hefei
country: China
facility: Local Institution - 0207
state: Anhui
city: Hefei
country: China
facility: Local Institution - 0197
state: Anhui
city: Beijing
country: China
facility: Local Institution - 0182
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0179
state: Beijing
city: Beijing
country: China
facility: Local Institution - 0216
state: Beijing
city: Fuzhou
country: China
facility: Local Institution - 0217
state: Fujian
city: Fuzhou
country: China
facility: Local Institution - 0219
state: Fujian
city: Shantou
country: China
facility: Local Institution - 0199
state: Guangdong
city: Harbin
country: China
facility: Local Institution - 0185
state: Heilongjiang
city: Zhengzhou
country: China
facility: Local Institution - 0193
state: Henan
city: Zhengzhou
country: China
facility: Local Institution - 0195
state: Henan
city: Zhengzhou
country: China
facility: Local Institution - 0194
state: Henan
city: Changsha
country: China
facility: Local Institution - 0249
state: Hunan
city: Changsha
country: China
facility: Local Institution - 0212
state: Hunan
city: Nanjing
country: China
facility: Local Institution - 0201
state: Jiangsu
city: Changchun
country: China
facility: Local Institution - 0180
state: Jilin
city: Xi'an
country: China
facility: Local Institution - 0183
state: Shan3xi
city: Shanghai
country: China
facility: Local Institution - 0215
state: Shanghai
city: Shanghai
country: China
facility: Local Institution - 0200
state: Shanghai
city: Hangzhou
country: China
facility: Local Institution - 0184
state: Zhejiang
city: Linhai
country: China
facility: Local Institution - 0247
state: Zhejiang
city: Shenyang
country: China
facility: Local Institution - 0220
city: Xi'An
country: China
facility: Local Institution - 0248
city: Bogota
country: Colombia
facility: Local Institution - 0059
city: Medellin
country: Colombia
facility: Local Institution - 0058
city: Monteria
country: Colombia
facility: Local Institution - 0224
city: Pereira
country: Colombia
facility: Local Institution - 0094
city: Brno
country: Czechia
facility: Local Institution - 0083
city: Brno
country: Czechia
facility: Local Institution - 0008
city: Novy Jicin
country: Czechia
facility: Local Institution - 0006
city: Odense
country: Denmark
facility: Local Institution - 0099
city: Lille
country: France
facility: Local Institution - 0116
state: Nord
city: Caen
country: France
facility: Local Institution - 0114
city: Montpellier
country: France
facility: Local Institution - 0112
city: Rennes Cedex
country: France
facility: Local Institution - 0113
city: Toulouse
country: France
facility: Local Institution - 0242
city: Villejuif
country: France
facility: Local Institution - 0115
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0035
city: Kowloon
country: Hong Kong
facility: Local Institution - 0070
city: Bergamo
country: Italy
facility: Local Institution - 0085
city: Milano
country: Italy
facility: Local Institution - 0039
city: Padova
country: Italy
facility: Local Institution - 0084
city: Pisa
country: Italy
facility: Local Institution - 0240
city: Akita-shi
country: Japan
facility: Local Institution - 0152
state: Akita
city: Hirosaki-shi
country: Japan
facility: Local Institution - 0104
state: Aomori
city: Kashiwa-shi
country: Japan
facility: Local Institution - 0173
state: Chiba
city: Matsuyama-shi
country: Japan
facility: Local Institution - 0169
state: Ehime
city: Matsuyama-shi
country: Japan
facility: Local Institution - 0119
state: Ehime
city: Fukuoka-shi
country: Japan
facility: Local Institution - 0174
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Local Institution - 0142
state: Fukuoka
city: Fukushima-shi
country: Japan
facility: Local Institution - 0103
state: Fukushima
city: Gifu City
country: Japan
facility: Local Institution - 0154
state: Gifu
city: Ota
country: Japan
facility: Local Institution - 0176
state: Gunma
city: Hiroshima-Shi
country: Japan
facility: Local Institution - 0100
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Local Institution - 0111
state: Hokkaido
city: Akashi-shi
country: Japan
facility: Local Institution - 0170
state: Hyogo
city: Kobe-shi
country: Japan
facility: Local Institution - 0118
state: Hyogo
city: Kobe
country: Japan
facility: Local Institution - 0172
state: Hyogo
city: Kanazawa
country: Japan
facility: Local Institution - 0171
state: Ishikawa
city: Kagoshima-shi
country: Japan
facility: Local Institution - 0229
state: Kagoshima
city: Isehara
country: Japan
facility: Local Institution - 0127
state: Kanagawa
city: Kawasaki-shi
country: Japan
facility: Local Institution - 0109
state: Kanagawa
city: Sagamihara-shi
country: Japan
facility: Local Institution - 0105
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Local Institution - 0147
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Local Institution - 0117
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Local Institution - 0141
state: Kumamoto
city: Kamigyo-ku
country: Japan
facility: Local Institution - 0120
state: Kyoto
city: Sendai
country: Japan
facility: Local Institution - 0144
state: Miyagi
city: Niigata-shi
country: Japan
facility: Local Institution - 0146
state: Niigata
city: Kurashiki-shi
country: Japan
facility: Local Institution - 0135
state: Okayama
city: Okayama-shi
country: Japan
facility: Local Institution - 0137
state: Okayama
city: Hirakata
country: Japan
facility: Local Institution - 0221
state: Osaka
city: Osaka-shi
country: Japan
facility: Local Institution - 0138
state: Osaka
city: Osakasayama
country: Japan
facility: Local Institution - 0098
state: Osaka
city: Suita
country: Japan
facility: Local Institution - 0107
state: Osaka
city: Takatsuki City
country: Japan
facility: Local Institution - 0139
state: Osaka
city: Hidaka-shi
country: Japan
facility: Local Institution - 0230
state: Saitama
city: Kitaadachi-gun
country: Japan
facility: Local Institution - 0175
state: Saitama
city: Sunto-gun
country: Japan
facility: Local Institution - 0143
state: Shizuoka
city: Shimotsuga-gun
country: Japan
facility: Local Institution - 0148
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0106
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0110
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0136
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0128
state: Tokyo
city: Koto-ku
country: Japan
facility: Local Institution - 0126
state: Tokyo
city: Minato-ku
country: Japan
facility: Local Institution - 0156
state: Tokyo
city: Ota-ku
country: Japan
facility: Local Institution - 0245
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Local Institution - 0140
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Local Institution - 0196
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Local Institution - 0155
state: Tokyo
city: Toyama-shi
country: Japan
facility: Local Institution - 0231
state: Toyama
city: Wakayama-shi
country: Japan
facility: Local Institution - 0178
state: Wakayama
city: Ube-shi
country: Japan
facility: Local Institution - 0238
state: Yamaguchi
city: Chiba
country: Japan
facility: Local Institution - 0101
city: Chiba
country: Japan
facility: Local Institution - 0153
city: Kyoto
country: Japan
facility: Local Institution - 0145
city: Shizuoka
country: Japan
facility: Local Institution - 0108
city: Seongnam-si
country: Korea, Republic of
facility: Local Institution - 0129
state: Kyǒnggi-do
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0165
state: Seoul-teukbyeolsi [Seoul]
city: Busan
country: Korea, Republic of
facility: Local Institution - 0166
city: Daegu
country: Korea, Republic of
facility: Local Institution - 0150
city: Daejeon
country: Korea, Republic of
facility: Local Institution - 0149
city: Jeonju-si
country: Korea, Republic of
facility: Local Institution - 0236
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0235
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0130
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0177
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0168
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0151
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0131
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0123
city: Ulsan
country: Korea, Republic of
facility: Local Institution - 0157
city: Tuxtla Gutierrez
country: Mexico
facility: Local Institution - 0090
state: Chiapas
city: Mexico
country: Mexico
facility: Local Institution - 0102
state: Distrito Federal
city: Merida
country: Mexico
facility: Local Institution - 0071
state: Yucatan
city: San Luis Potosi
country: Mexico
facility: Local Institution - 0234
city: Callao
country: Peru
facility: Local Institution - 0092
city: Lima
country: Peru
facility: Local Institution - 0060
city: Lima
country: Peru
facility: Local Institution - 0093
city: Lublin
country: Poland
facility: Local Institution - 0024
city: Warszawa
country: Poland
facility: Local Institution - 0022
city: Porto
country: Portugal
facility: Local Institution - 0243
city: Bucuresti
country: Romania
facility: Local Institution - 0081
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0079
city: Craiova
country: Romania
facility: Local Institution - 0076
city: Suceava
country: Romania
facility: Local Institution - 0080
city: Moscow
country: Russian Federation
facility: Local Institution - 0089
city: St Petersburg
country: Russian Federation
facility: Local Institution - 0088
city: Singapore
country: Singapore
facility: Local Institution - 0033
state: Central Singapore
city: Singapore
country: Singapore
facility: Local Institution - 0034
city: Barcelona
country: Spain
facility: Local Institution - 0063
city: Madrid
country: Spain
facility: Local Institution - 0062
city: Changhua County
country: Taiwan
facility: Local Institution - 0158
state: Changhua
city: Tainan
country: Taiwan
facility: Local Institution - 0161
state: TNN
city: Kaohsiung County
country: Taiwan
facility: Local Institution - 0163
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0167
city: Kaohsiung
country: Taiwan
facility: Local Institution - 0133
city: Keelung
country: Taiwan
facility: Local Institution - 0164
city: Taichung
country: Taiwan
facility: Local Institution - 0132
city: Tainan
country: Taiwan
facility: Local Institution - 0160
city: Taipei
country: Taiwan
facility: Local Institution - 0124
city: Taipei
country: Taiwan
facility: Local Institution - 0162
city: Taipei
country: Taiwan
facility: Local Institution - 0134
city: Taoyuan
country: Taiwan
facility: Local Institution - 0159
city: Ankara
country: Turkey
facility: Local Institution - 0096
city: Diyarbakır
country: Turkey
facility: Local Institution - 0125
city: Edrine
country: Turkey
facility: Local Institution - 0122
city: London
country: United Kingdom
facility: Local Institution - 0069
state: Greater London
city: London
country: United Kingdom
facility: Local Institution - 0066
state: Greater London
city: Manchester
country: United Kingdom
facility: Local Institution - 0031
state: Greater Manchester
city: London
country: United Kingdom
facility: Local Institution - 0237
city: Surrey
country: United Kingdom
facility: Local Institution - 0029
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Kato K, Doki Y, Ogata T, Motoyama S, Kawakami H, Ueno M, Kojima T, Shirakawa Y, Okada M, Ishihara R, Kubota Y, Amaya-Chanaga C, Chen T, Matsumura Y, Kitagawa Y. First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50). Esophagus. 2023 Apr;20(2):291-301. doi: 10.1007/s10388-022-00970-1. Epub 2022 Nov 19.
citation: Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu CH, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Ostoich SA, Kim HR, Ueno M, Mansoor W, Yang WC, Liu T, Bridgewater J, Makino T, Xynos I, Liu X, Lei M, Kondo K, Patel A, Gricar J, Chau I, Kitagawa Y; CheckMate 648 Trial Investigators. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022 Feb 3;386(5):449-462. doi: 10.1056/NEJMoa2111380.