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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 (CheckMate 648)

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ClinicalTrials.gov Identifier: NCT03143153
Recruitment Status : Active, not recruiting
First Posted : May 8, 2017
Results First Posted : March 2, 2022
Last Update Posted : December 4, 2023
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
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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

Condition or disease Intervention/treatment Phase
Various Advanced Cancer Biological: Nivolumab Biological: Ipilimumab Drug: Cisplatin Drug: Fluorouracil Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 970 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 29, 2017
Actual Primary Completion Date : January 18, 2021
Estimated Study Completion Date : January 13, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Nivolumab + Ipilimumab Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558 (Nivolumab)
  • Opdivo (Nivolumab)

Biological: Ipilimumab
Specified dose on specified days
Other Names:
  • BMS-734016 (Ipilimumab)
  • Yervoy (Ipilimumab)
Experimental: Nivolumab + Cisplatin + Fluorouacil Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558 (Nivolumab)
  • Opdivo (Nivolumab)

Drug: Cisplatin
Specified dose on specified days

Drug: Fluorouracil
Specified dose on specified days
Active Comparator: Cisplatin + Fluorouracil Drug: Cisplatin
Specified dose on specified days

Drug: Fluorouracil
Specified dose on specified days


Outcome Measures
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Primary Outcome Measures :
  1. Overall Survival (OS) in Participants With Tumor Cell PD-L1 [ Time Frame: From the date of randomization to up to the date of death (up to approximately 20 months) ]
    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.

  2. Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1 [ Time Frame: From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 9 months) ]
    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.


Secondary Outcome Measures :
  1. Overall Survival (OS) in All Randomized Participants [ Time Frame: From the date of randomization to up to the date of death (up to approximately 16 months) ]
    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.

  2. Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR [ Time Frame: From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 7 months) ]
    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.

  3. Objective Response Rate (ORR) as Assessed by BICR [ Time Frame: 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) ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03143153


Locations
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Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] October 29, 2020
Statistical Analysis Plan  [PDF] February 23, 2021

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03143153    
Other Study ID Numbers: CA209-648
2016-001514-20 ( EudraCT Number )
First Posted: May 8, 2017    Key Record Dates
Results First Posted: March 2, 2022
Last Update Posted: December 4, 2023
Last Verified: November 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Nivolumab
Fluorouracil
Ipilimumab
Antineoplastic Agents
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
 Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs