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

Various Advanced Cancer Clinical Trial

— CheckMate 648  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03143153
• Other study ID #: CA209-648
• Secondary ID: 2016-001514-20
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 29, 2017
• Est. completion date: January 13, 2025

Study information

• Verified date: November 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 970
• Est. completion date: January 13, 2025
• Est. primary completion date: January 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Various Advanced Cancer

Intervention

Biological:
• Nivolumab
Specified dose on specified days
• Ipilimumab
Specified dose on specified days

Drug:
• Cisplatin
Specified dose on specified days
• Fluorouracil
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0048	Buenos Aires
Argentina	Local Institution - 0050	Capital Federal	Buenos Aires
Argentina	Local Institution - 0087	La Rioja
Argentina	Local Institution - 0086	Rosario	Santa FE
Australia	Local Institution - 0011	Douglas	Queensland
Australia	Local Institution - 0010	Murdoch	Western Australia
Australia	Local Institution - 0232	Tamworth	New South Wales
Austria	Local Institution - 0241	Salzburg
Brazil	Local Institution - 0019	Barretos	Sao Paulo
Brazil	Local Institution - 0021	Ijui	RIO Grande DO SUL
Brazil	Local Institution - 0227	Ipatinga	Minas Gerais
Brazil	Local Institution - 0226	Jau	Sao Paulo
Brazil	Local Institution - 0016	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0228	Rio de Janeiro
Brazil	Local Institution - 0017	Salvador	Bahia
Brazil	Local Institution - 0018	São José do Rio Preto	São Paulo
Brazil	Local Institution - 0020	Sao Paulo
Canada	Local Institution - 0095	Moncton	New Brunswick
Canada	Local Institution - 0082	Montreal	Quebec
Canada	Local Institution - 0222	Montreal	Quebec
Canada	Local Institution - 0037	Trois-Rivieres	Quebec
Chile	Local Institution - 0053	Santiago	Metropolitana
Chile	Local Institution - 0214	Santiago	Metropolitana
China	Local Institution - 0179	Beijing	Beijing
China	Local Institution - 0182	Beijing	Beijing
China	Local Institution - 0216	Beijing	Beijing
China	Local Institution - 0180	Changchun	Jilin
China	Local Institution - 0212	Changsha	Hunan
China	Local Institution - 0249	Changsha	Hunan
China	Local Institution - 0217	Fuzhou	Fujian
China	Local Institution - 0219	Fuzhou	Fujian
China	Local Institution - 0184	Hangzhou	Zhejiang
China	Local Institution - 0185	Harbin	Heilongjiang
China	Local Institution - 0197	Hefei	Anhui
China	Local Institution - 0207	Hefei	Anhui
China	Local Institution - 0247	Linhai	Zhejiang
China	Local Institution - 0201	Nanjing	Jiangsu
China	Local Institution - 0200	Shanghai	Shanghai
China	Local Institution - 0215	Shanghai	Shanghai
China	Local Institution - 0199	Shantou	Guangdong
China	Local Institution - 0220	Shenyang
China	Local Institution - 0183	Xi'an	Shan3xi
China	Local Institution - 0248	Xi'An
China	Local Institution - 0193	Zhengzhou	Henan
China	Local Institution - 0194	Zhengzhou	Henan
China	Local Institution - 0195	Zhengzhou	Henan
Colombia	Local Institution - 0059	Bogota
Colombia	Local Institution - 0058	Medellin
Colombia	Local Institution - 0224	Monteria
Colombia	Local Institution - 0094	Pereira
Czechia	Local Institution - 0008	Brno
Czechia	Local Institution - 0083	Brno
Czechia	Local Institution - 0006	Novy Jicin
Denmark	Local Institution - 0099	Odense
France	Local Institution - 0114	Caen
France	Local Institution - 0116	Lille	Nord
France	Local Institution - 0112	Montpellier
France	Local Institution - 0113	Rennes Cedex
France	Local Institution - 0242	Toulouse
France	Local Institution - 0115	Villejuif
Hong Kong	Local Institution - 0035	Hong Kong
Hong Kong	Local Institution - 0070	Kowloon
Italy	Local Institution - 0085	Bergamo
Italy	Local Institution - 0039	Milano
Italy	Local Institution - 0084	Padova
Italy	Local Institution - 0240	Pisa
Japan	Local Institution - 0170	Akashi-shi	Hyogo
Japan	Local Institution - 0152	Akita-shi	Akita
Japan	Local Institution - 0106	Bunkyo-ku	Tokyo
Japan	Local Institution - 0110	Bunkyo-ku	Tokyo
Japan	Local Institution - 0101	Chiba
Japan	Local Institution - 0153	Chiba
Japan	Local Institution - 0128	Chuo-ku	Tokyo
Japan	Local Institution - 0136	Chuo-ku	Tokyo
Japan	Local Institution - 0142	Fukuoka-shi	Fukuoka
Japan	Local Institution - 0174	Fukuoka-shi	Fukuoka
Japan	Local Institution - 0103	Fukushima-shi	Fukushima
Japan	Local Institution - 0154	Gifu City	Gifu
Japan	Local Institution - 0230	Hidaka-shi	Saitama
Japan	Local Institution - 0221	Hirakata	Osaka
Japan	Local Institution - 0104	Hirosaki-shi	Aomori
Japan	Local Institution - 0100	Hiroshima-Shi	Hiroshima
Japan	Local Institution - 0127	Isehara	Kanagawa
Japan	Local Institution - 0229	Kagoshima-shi	Kagoshima
Japan	Local Institution - 0120	Kamigyo-ku	Kyoto
Japan	Local Institution - 0171	Kanazawa	Ishikawa
Japan	Local Institution - 0173	Kashiwa-shi	Chiba
Japan	Local Institution - 0109	Kawasaki-shi	Kanagawa
Japan	Local Institution - 0175	Kitaadachi-gun	Saitama
Japan	Local Institution - 0172	Kobe	Hyogo
Japan	Local Institution - 0118	Kobe-shi	Hyogo
Japan	Local Institution - 0126	Koto-ku	Tokyo
Japan	Local Institution - 0141	Kumamoto-shi	Kumamoto
Japan	Local Institution - 0135	Kurashiki-shi	Okayama
Japan	Local Institution - 0145	Kyoto
Japan	Local Institution - 0119	Matsuyama-shi	Ehime
Japan	Local Institution - 0169	Matsuyama-shi	Ehime
Japan	Local Institution - 0156	Minato-ku	Tokyo
Japan	Local Institution - 0146	Niigata-shi	Niigata
Japan	Local Institution - 0137	Okayama-shi	Okayama
Japan	Local Institution - 0138	Osaka-shi	Osaka
Japan	Local Institution - 0098	Osakasayama	Osaka
Japan	Local Institution - 0176	Ota	Gunma
Japan	Local Institution - 0245	Ota-ku	Tokyo
Japan	Local Institution - 0105	Sagamihara-shi	Kanagawa
Japan	Local Institution - 0111	Sapporo-shi	Hokkaido
Japan	Local Institution - 0144	Sendai	Miyagi
Japan	Local Institution - 0148	Shimotsuga-gun	Tochigi
Japan	Local Institution - 0140	Shinagawa-ku	Tokyo
Japan	Local Institution - 0155	Shinjuku-ku	Tokyo
Japan	Local Institution - 0196	Shinjuku-Ku	Tokyo
Japan	Local Institution - 0108	Shizuoka
Japan	Local Institution - 0107	Suita	Osaka
Japan	Local Institution - 0143	Sunto-gun	Shizuoka
Japan	Local Institution - 0139	Takatsuki City	Osaka
Japan	Local Institution - 0231	Toyama-shi	Toyama
Japan	Local Institution - 0238	Ube-shi	Yamaguchi
Japan	Local Institution - 0178	Wakayama-shi	Wakayama
Japan	Local Institution - 0117	Yokohama-shi	Kanagawa
Japan	Local Institution - 0147	Yokohama-shi	Kanagawa
Korea, Republic of	Local Institution - 0166	Busan
Korea, Republic of	Local Institution - 0150	Daegu
Korea, Republic of	Local Institution - 0149	Daejeon
Korea, Republic of	Local Institution - 0236	Jeonju-si
Korea, Republic of	Local Institution - 0129	Seongnam-si	Kyonggi-do
Korea, Republic of	Local Institution - 0123	Seoul
Korea, Republic of	Local Institution - 0130	Seoul
Korea, Republic of	Local Institution - 0131	Seoul
Korea, Republic of	Local Institution - 0151	Seoul
Korea, Republic of	Local Institution - 0165	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Local Institution - 0168	Seoul
Korea, Republic of	Local Institution - 0177	Seoul
Korea, Republic of	Local Institution - 0235	Seoul
Korea, Republic of	Local Institution - 0157	Ulsan
Mexico	Local Institution - 0071	Merida	Yucatan
Mexico	Local Institution - 0102	Mexico	Distrito Federal
Mexico	Local Institution - 0234	San Luis Potosi
Mexico	Local Institution - 0090	Tuxtla Gutierrez	Chiapas
Peru	Local Institution - 0092	Callao
Peru	Local Institution - 0060	Lima
Peru	Local Institution - 0093	Lima
Poland	Local Institution - 0024	Lublin
Poland	Local Institution - 0022	Warszawa
Portugal	Local Institution - 0243	Porto
Romania	Local Institution - 0081	Bucuresti
Romania	Local Institution - 0079	Cluj-Napoca
Romania	Local Institution - 0076	Craiova
Romania	Local Institution - 0080	Suceava
Russian Federation	Local Institution - 0089	Moscow
Russian Federation	Local Institution - 0088	St Petersburg
Singapore	Local Institution - 0033	Singapore	Central Singapore
Singapore	Local Institution - 0034	Singapore
Spain	Local Institution - 0063	Barcelona
Spain	Local Institution - 0062	Madrid
Taiwan	Local Institution - 0158	Changhua
Taiwan	Local Institution - 0133	Kaohsiung
Taiwan	Local Institution - 0167	Kaohsiung
Taiwan	Local Institution - 0163	Kaohsiung County
Taiwan	Local Institution - 0164	Keelung
Taiwan	Local Institution - 0132	Taichung
Taiwan	Local Institution - 0160	Tainan
Taiwan	Local Institution - 0161	Tainan	TNN
Taiwan	Local Institution - 0124	Taipei
Taiwan	Local Institution - 0134	Taipei
Taiwan	Local Institution - 0162	Taipei
Taiwan	Local Institution - 0159	Taoyuan
Turkey	Local Institution - 0096	Ankara
Turkey	Local Institution - 0125	Diyarbakir
Turkey	Local Institution - 0122	Edrine
United Kingdom	Local Institution - 0066	London	Greater London
United Kingdom	Local Institution - 0069	London	Greater London
United Kingdom	Local Institution - 0237	London
United Kingdom	Local Institution - 0031	Manchester	Greater Manchester
United Kingdom	Local Institution - 0029	Surrey
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Oncology Associates Of Oregon, Pc	Eugene	Oregon
United States	Local Institution - 0028	Houston	Texas
United States	Usc/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Northwest Georgia Oncology Center, P.C.	Marietta	Georgia
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida
United States	University Of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Southern Cancer Center, Inc.	Mobile	Alabama
United States	Local Institution - 0203	Morgantown	West Virginia
United States	Hackensack Meridian Jersey Shore University Medical Center	Neptune	New Jersey
United States	Northwest Cancer Specialists, P.C.	Portland	Oregon
United States	Oncology & Hematology Associates Of Southwest Virginia, Inc.	Roanoke	Virginia
United States	Moffitt Cancer Center	Tampa	Florida
United States	Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  Denmark,  France,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in Participants With Tumor Cell PD-L1	Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the subject was known to be alive.	From the date of randomization to up to the date of death (up to approximately 20 months)
Primary	Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1	Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented progressive disease (PD) per Blinded Independent Central Review (BICR) or death due to any cause. Participants who die without a reported prior PD per BICR (and die without start of subsequent therapy) will be considered to have progressed on the date of death. Participants who did not have documented PD per BICR per RECIST1.1 criteria and who did not die, will be censored at the date of the last evaluable tumor assessment on or prior to initiation of the subsequent anti-cancer therapy. Participants who did not have any on-study tumor assessments and did not die (or died after initiation of the subsequent anti-cancer therapy) will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported PD per BICR will be censored at the last tumor assessment on or prior to initiation of the subsequent anti-cancer therapy.	From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 9 months)
Secondary	Overall Survival (OS) in All Randomized Participants	Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the subject was known to be alive.	From the date of randomization to up to the date of death (up to approximately 16 months)
Secondary	Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR	Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented progressive disease (PD) per Blinded Independent Central Review (BICR) or death due to any cause. Participants who die without a reported prior PD per BICR (and die without start of subsequent therapy) will be considered to have progressed on the date of death. Participants who did not have documented PD per BICR per RECIST1.1 criteria and who did not die, will be censored at the date of the last evaluable tumor assessment on or prior to initiation of the subsequent anti-cancer therapy. Participants who did not have any on-study tumor assessments and did not die (or died after initiation of the subsequent anti-cancer therapy) will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported PD per BICR will be censored at the last tumor assessment on or prior to initiation of the subsequent anti-cancer therapy.	From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 7 months)
Secondary	Objective Response Rate (ORR) as Assessed by BICR	Objective response rate (ORR) is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation as determined by BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1) or the date of subsequent anti-cancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions. Complete response is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to <10 mm.	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)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls