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Nivolumab Plus Epacadostat in Combination With Chemotherapy Versus the EXTREME Regimen in Squamous Cell Carcinoma of the Head and Neck (CheckMate 9NA/ECHO-310)

Primary Purpose

Head and Neck Cancer

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Nivolumab
Epacadostat
Placebo
Carboplatin
Cisplatin
Cetuximab
5-Fluorouracil
Sponsored by
Incyte Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring Squamous cell carcinoma of the head and neck, programmed cell death protein 1 (PD-1) antibody, indoleamine 2,3-dioxygenase (IDO) inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed SCCHN from any of the following primary sites: oral cavity, oropharynx, hypopharynx, and larynx.
  • Must have recurrent or metastatic disease that is not amenable to therapy with curative intent (surgery and/or radiation therapy with or without chemotherapy).
  • No prior treatment with systemic anti-cancer therapy for SCCHN unless protocol-defined conditions are met.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to1.
  • Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1.
  • Documentation of program death ligand-1 (PD-L1) status prior to randomization.

Exclusion Criteria:

  • Recurrent or metastatic carcinoma of the nasopharynx and paranasal sinuses, squamous cell carcinoma that originated from the skin and salivary gland or non-squamous histologies (e.g., mucosal melanoma) and SCCHN of unknown primary origin.
  • Untreated central nervous system (CNS) metastases.
  • Carcinomatous meningitis.
  • Active, known or suspected autoimmune disease.
  • Physical and laboratory test findings outside the protocol-defined range.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Active Comparator

    Experimental

    Arm Label

    Arm A

    Arm B

    Arm C

    Arm Description

    Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.

    EXTREME regimen.

    Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.

    Outcomes

    Primary Outcome Measures

    Progression-free survival (PFS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
    Defined as the time between the date of randomization and the date of first documented disease progression (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) or death due to any cause, whichever occurs first.
    Overall survival (OS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
    Defined as the time between the date of randomization and the date of death.

    Secondary Outcome Measures

    Objective response rate (ORR) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) and the EXTREME regimen (Arm B)
    Defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.
    Duration of response (DOR) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) and the EXTREME regimen (Arm B)
    Defined as the time between the date of first documented response (CR or PR per RECIST v1.1) to the date of the first disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
    ORR with nivolumab plus placebo in combination with chemotherapy (Arm C)
    Defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.
    PFS with nivolumab plus placebo in combination with chemotherapy (Arm C)
    Defined as the time between the date of randomization and the date of first documented disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
    DOR with nivolumab plus placebo in combination with chemotherapy (Arm C)
    Defined as the time between the date of first documented response (CR or PR per RECIST v1.1) to the date of the first disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
    Time to meaningful symptomatic deterioration (TTSD) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
    TTSD assessed by the 10-item Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) Symptom Index (FHNSI-10).

    Full Information

    First Posted
    November 9, 2017
    Last Updated
    December 19, 2019
    Sponsor
    Incyte Corporation
    Collaborators
    Bristol-Myers Squibb
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03342352
    Brief Title
    Nivolumab Plus Epacadostat in Combination With Chemotherapy Versus the EXTREME Regimen in Squamous Cell Carcinoma of the Head and Neck (CheckMate 9NA/ECHO-310)
    Official Title
    A Randomized, Global, Phase 3 Trial of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Platinum + 5-fluorouracil) Versus the EXTREME Regimen (Cetuximab + Platinum + 5-fluorouracil) in First-line Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) / CheckMate 9NA /ECHO-310
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2019
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Study was cancelled prior to enrolling any patients.
    Study Start Date
    December 15, 2017 (Actual)
    Primary Completion Date
    April 20, 2018 (Actual)
    Study Completion Date
    April 20, 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Incyte Corporation
    Collaborators
    Bristol-Myers Squibb

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the safety and efficacy of the combination of nivolumab plus epacadostat in combination with chemotherapy in first-line recurrent or metastatic patients with squamous cell carcinoma of the head and neck (SCCHN) when compared to the standard of care (EXTREME regimen).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Head and Neck Cancer
    Keywords
    Squamous cell carcinoma of the head and neck, programmed cell death protein 1 (PD-1) antibody, indoleamine 2,3-dioxygenase (IDO) inhibitor

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm A
    Arm Type
    Experimental
    Arm Description
    Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
    Arm Title
    Arm B
    Arm Type
    Active Comparator
    Arm Description
    EXTREME regimen.
    Arm Title
    Arm C
    Arm Type
    Experimental
    Arm Description
    Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
    Intervention Type
    Drug
    Intervention Name(s)
    Nivolumab
    Intervention Description
    Nivolumab administered intravenously at the protocol-defined dose every 3 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Epacadostat
    Other Intervention Name(s)
    INCB024360
    Intervention Description
    Epacadostat administered orally at the protocol-defined dose twice daily.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Matching placebo for epacadostat administered orally twice daily.
    Intervention Type
    Drug
    Intervention Name(s)
    Carboplatin
    Intervention Description
    Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin
    Intervention Description
    Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.
    Intervention Type
    Drug
    Intervention Name(s)
    Cetuximab
    Intervention Description
    Cetuximab administered intravenously at the protocol-defined dose weekly.
    Intervention Type
    Drug
    Intervention Name(s)
    5-Fluorouracil
    Intervention Description
    5-Fluorouracil administered intravenously at the protocol-defined dose on Days 1-4 for 6 cycles.
    Primary Outcome Measure Information:
    Title
    Progression-free survival (PFS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
    Description
    Defined as the time between the date of randomization and the date of first documented disease progression (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) or death due to any cause, whichever occurs first.
    Time Frame
    Up to approximately 35 months
    Title
    Overall survival (OS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
    Description
    Defined as the time between the date of randomization and the date of death.
    Time Frame
    Up to approximately 48 months
    Secondary Outcome Measure Information:
    Title
    Objective response rate (ORR) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) and the EXTREME regimen (Arm B)
    Description
    Defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.
    Time Frame
    Up to approximately 35 months
    Title
    Duration of response (DOR) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) and the EXTREME regimen (Arm B)
    Description
    Defined as the time between the date of first documented response (CR or PR per RECIST v1.1) to the date of the first disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
    Time Frame
    Up to approximately 35 months
    Title
    ORR with nivolumab plus placebo in combination with chemotherapy (Arm C)
    Description
    Defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.
    Time Frame
    Up to approximately 35 months
    Title
    PFS with nivolumab plus placebo in combination with chemotherapy (Arm C)
    Description
    Defined as the time between the date of randomization and the date of first documented disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
    Time Frame
    Up to approximately 35 months
    Title
    DOR with nivolumab plus placebo in combination with chemotherapy (Arm C)
    Description
    Defined as the time between the date of first documented response (CR or PR per RECIST v1.1) to the date of the first disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first.
    Time Frame
    Up to approximately 35 months
    Title
    Time to meaningful symptomatic deterioration (TTSD) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
    Description
    TTSD assessed by the 10-item Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) Symptom Index (FHNSI-10).
    Time Frame
    Up to approximately 60 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically confirmed SCCHN from any of the following primary sites: oral cavity, oropharynx, hypopharynx, and larynx. Must have recurrent or metastatic disease that is not amenable to therapy with curative intent (surgery and/or radiation therapy with or without chemotherapy). No prior treatment with systemic anti-cancer therapy for SCCHN unless protocol-defined conditions are met. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to1. Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1. Documentation of program death ligand-1 (PD-L1) status prior to randomization. Exclusion Criteria: Recurrent or metastatic carcinoma of the nasopharynx and paranasal sinuses, squamous cell carcinoma that originated from the skin and salivary gland or non-squamous histologies (e.g., mucosal melanoma) and SCCHN of unknown primary origin. Untreated central nervous system (CNS) metastases. Carcinomatous meningitis. Active, known or suspected autoimmune disease. Physical and laboratory test findings outside the protocol-defined range.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Vinny Hayreh, MD
    Organizational Affiliation
    Bristol-Myers Squibb Research and Development
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Nivolumab Plus Epacadostat in Combination With Chemotherapy Versus the EXTREME Regimen in Squamous Cell Carcinoma of the Head and Neck (CheckMate 9NA/ECHO-310)

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