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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
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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
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Secondary ID [1]
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2016-001514-20
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Secondary ID [2]
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CA209-648
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Universal Trial Number (UTN)
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Trial acronym
CheckMate 648
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Various Advanced Cancer
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0
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Condition category
Condition code
Intervention/exposure
Study type
Interventional(has expanded access)
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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
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Intervention code [1]
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Treatment: Other
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Overall Survival (OS) in Participants With Tumor Cell PD-L1
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Assessment method [1]
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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.
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Timepoint [1]
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From the date of randomization to up to the date of death (up to approximately 20 months)
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Primary outcome [2]
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Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1
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Assessment method [2]
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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.
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Timepoint [2]
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From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 9 months)
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Secondary outcome [1]
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Overall Survival (OS) in All Randomized Participants
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Assessment method [1]
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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.
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Timepoint [1]
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From the date of randomization to up to the date of death (up to approximately 16 months)
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Secondary outcome [2]
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Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR
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Assessment method [2]
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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.
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Timepoint [2]
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From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 7 months)
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Secondary outcome [3]
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Objective Response Rate (ORR) as Assessed by BICR
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Assessment method [3]
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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.
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Timepoint [3]
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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)
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
29/06/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
13/01/2025
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Actual
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Sample size
Target
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Accrual to date
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Final
970
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
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Recruitment hospital [1]
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Local Institution - 0232 - Tamworth
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Local Institution - 0011 - Douglas
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Local Institution - 0010 - Murdoch
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2340 - Tamworth
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4814 - Douglas
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6150 - Murdoch
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Recruitment outside Australia
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Turkey
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State/province [122]
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Diyarbakir
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Turkey
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Edrine
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United Kingdom
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State/province [124]
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Greater London
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United Kingdom
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Greater Manchester
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United Kingdom
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London
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Country [127]
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United Kingdom
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State/province [127]
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Surrey
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Bristol-Myers Squibb
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Commercial sector/industry
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Ono Pharmaceutical Co. Ltd
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Ethics approval
Ethics application status
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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
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Trial website
https://clinicaltrials.gov/study/NCT03143153
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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.
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Public notes
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Contacts
Principal investigator
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Bristol-Myers Squibb
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Bristol-Myers Squibb
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Contact person for public queries
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
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Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/53/NCT03143153/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/53/NCT03143153/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03143153
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