Study of Nivolumab in Combination With Ipilimumab Compared to the Standard of Care (Extreme Regimen) as First Line Treatment in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Phase 3

Completed

Conditions: Head and Neck Cancer

Interventions: Biological: Nivolumab
Drug: Cetuximab/Erbitux
Biological: Ipilimumab
Drug: Cisplatin/Platinol
Drug: Carboplatin/Paraplatin
Drug: Fluorouracil/Adrucil

Registration Number: NCT02741570

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The main purpose of this study is to compare nivolumab and ipilimumab with the extreme regimen as first line treatment in patients with recurrent or metastatic squamous cell of the head and neck cancer

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 947

Inclusion Criteria

Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx & larynx) that is not amenable to curative therapy.
No prior systemic cancer therapy for recurrent or metastatic disease (except if chemotherapy was part of multimodal treatment completed 6 months prior to enrolment).
Measurable disease detected by imaging exam (CT or MRI).
Have tumor tissue for PD L1 expression testing, and for oropharyngeal cancer have results from testing of HPV p16 status.

Exclusion Criteria

Metastatic or recurrent carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, squamous cell carcinoma originating from skin and salivary glands or non squamous histologies (eg. mucosal melanoma).
No prior treatment with anti PD1, anti PD L1, anti CTLA 4 antibody or any other antibody or drugs targeting T cell costimulation or checkpoint pathways, or cetuximab or EGFR inhibitors in any treatment setting.
Participants with certain diseases such as active autoimmune disease, type I diabetes, hypothyroidism that needs hormone replacement, active infection, psychiatric disorder.
Inadequate hematologic, renal or hepatic function.

Other protocol defined inclusion/exclusion criteria could apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Extreme Regimen	Carboplatin/Paraplatin	Specified dose on specified days
Nivolumab and Ipilimumab	Nivolumab	Specified dose on specified days
Nivolumab and Ipilimumab	Ipilimumab	Specified dose on specified days
Extreme Regimen	Cetuximab/Erbitux	Specified dose on specified days
Extreme Regimen	Cisplatin/Platinol	Specified dose on specified days
Extreme Regimen	Fluorouracil/Adrucil	Specified dose on specified days

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20	From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)	Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates)
Overall Survival (OS) in All Randomized Participants	From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)	Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates)

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1	From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)	Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates)
Progression Free Survival (PFS)	From randomization to disease progression or death (Up to approximately 65 months)	PFS is defined as the time between the date of randomization and the date of first documented tumor progression, based on Blinded Independent Central Review (BICR) assessments (per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria), or death due to any cause, whichever occurs first. Participants who neither progress nor die will be censored on the date of their last tumor assessment. Participants who receive subsequent anti-cancer therapy prior to documented progression, will be censored on the date of their last tumor assessment prior to subsequent therapy. (Based on Kaplan-Meier Estimates) Progression is defined as at least a 20% increase in the sum of diameters of target lesions, in addition the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Duration of Objective Response (DOR)	From randomization to the first documented response (CR or PR) and progression (up to approximately 65 months)	The time between the first documented response (Complete response (CR) or partial response (PR)) and progression or death, per RECIST 1.1 by blinded independent central review (BICR) assessment. (Based on Kaplan-Meier Estimates) Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Objective Response Rate (ORR)	From randomization up to approximately 65 months	Objective Response Rate (ORR) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by blinded independent central review (BICR) assessment. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Trial Locations

Locations (132): Local Institution - 0134
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Tucson, Arizona, United States
Local Institution - 0135
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Duarte, California, United States
Local Institution - 0005
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Stanford, California, United States
Local Institution - 0028
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Jacksonville, Florida, United States
Local Institution - 0008
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Tampa, Florida, United States
Local Institution - 0111
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Atlanta, Georgia, United States
Local Institution - 0006
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Chicago, Illinois, United States
Local Institution - 0001
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Boston, Massachusetts, United States
Local Institution - 0080
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Boston, Massachusetts, United States
Local Institution - 0093
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Boston, Massachusetts, United States
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Local Institution - 0134
🇺🇸Tucson, Arizona, United States