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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03143153




Registration number
NCT03143153
Ethics application status
Date submitted
4/05/2017
Date registered
8/05/2017
Date last updated
4/12/2023

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2016-001514-20
Secondary ID [2] 0 0
CA209-648
Universal Trial Number (UTN)
Trial acronym
CheckMate 648
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Various Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Other - Nivolumab
Treatment: Other - Ipilimumab
Treatment: Drugs - Cisplatin
Treatment: Drugs - Fluorouracil

Experimental: Nivolumab + Ipilimumab -

Experimental: Nivolumab + Cisplatin + Fluorouacil -

Active comparator: Cisplatin + Fluorouracil -


Treatment: Other: Nivolumab
Specified dose on specified days

Treatment: Other: Ipilimumab
Specified dose on specified days

Treatment: Drugs: Cisplatin
Specified dose on specified days

Treatment: Drugs: Fluorouracil
Specified dose on specified days
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) in Participants With Tumor Cell PD-L1
Timepoint [1] 0 0
From the date of randomization to up to the date of death (up to approximately 20 months)
Primary outcome [2] 0 0
Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1
Timepoint [2] 0 0
From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 9 months)
Secondary outcome [1] 0 0
Overall Survival (OS) in All Randomized Participants
Timepoint [1] 0 0
From the date of randomization to up to the date of death (up to approximately 16 months)
Secondary outcome [2] 0 0
Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR
Timepoint [2] 0 0
From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 7 months)
Secondary outcome [3] 0 0
Objective Response Rate (ORR) as Assessed by BICR
Timepoint [3] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
13/01/2025
Actual
Sample size
Target
Accrual to date
Final
970
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Local Institution - 0232 - Tamworth
Recruitment hospital [2] 0 0
Local Institution - 0011 - Douglas
Recruitment hospital [3] 0 0
Local Institution - 0010 - Murdoch
Recruitment postcode(s) [1] 0 0
2340 - Tamworth
Recruitment postcode(s) [2] 0 0
4814 - Douglas
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment outside Australia
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Santa FE
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La Rioja
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Austria
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Salzburg
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Greater Manchester
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London
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United Kingdom
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Surrey

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
Ono Pharmaceutical Co. Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT03143153
Trial related presentations / publications
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.
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.
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/NCT03143153