NCT02741570 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2023-09-21

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20

→

outcome · POSTED

Overall Survival (OS) in All Randomized Participants

→

outcome · POSTED

Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1

→

outcome · POSTED

Progression Free Survival (PFS)

→

outcome · POSTED

Objective Response Rate (ORR)

→

outcome · POSTED

Duration of Objective Response (DOR)

→

outcome · POSTED

Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20 - Extended Collection

→

outcome · POSTED

Overall Survival (OS) in All Randomized Participants - Extended Collection

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Specified dose on specified days
intervention Names
Biological: Nivolumab
Biological: Ipilimumab
label
Nivolumab and Ipilimumab
type
EXPERIMENTAL
description
Specified dose on specified days
intervention Names
Drug: Cetuximab/Erbitux
Drug: Cisplatin/Platinol
Drug: Carboplatin/Paraplatin
Drug: Fluorouracil/Adrucil
label
Extreme Regimen
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Nivolumab and Ipilimumab
name
Nivolumab
other Names
BMS-936558
Opdivo
type
BIOLOGICAL
arm Group Labels
Nivolumab and Ipilimumab
name
Ipilimumab
other Names
BMS-734016
Yervoy
type
BIOLOGICAL
arm Group Labels
Extreme Regimen
name
Cetuximab/Erbitux
type
DRUG
arm Group Labels
Extreme Regimen
name
Cisplatin/Platinol
type
DRUG
arm Group Labels
Extreme Regimen
name
Carboplatin/Paraplatin
type
DRUG
arm Group Labels
Extreme Regimen
name
Fluorouracil/Adrucil
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 947
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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)
measure
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20
time Frame
From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)
description
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)
measure
Overall Survival (OS) in All Randomized Participants
time Frame
From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)

secondary Outcomes

description
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)
measure
Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1
time Frame
From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)
description
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).
measure
Progression Free Survival (PFS)
time Frame
From randomization to disease progression or death (Up to approximately 65 months)
description
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.
measure
Objective Response Rate (ORR)
time Frame
From randomization up to approximately 65 months
description
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.
measure
Duration of Objective Response (DOR)
time Frame
From randomization to the first documented response (CR or PR) and progression (up to approximately 65 months)

Full study description

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

Source references

references

citation
Haddad RI, Harrington K, Tahara M, Ferris RL, Gillison M, Fayette J, Daste A, Koralewski P, Zurawski B, Taberna M, Saba NF, Mak M, Kawecki A, Girotto G, Alvarez Avitia MA, Even C, Toledo JGR, Guminski A, Muller-Richter U, Kiyota N, Roberts M, Khan TA, Miller-Moslin K, Wei L, Argiris A. Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651. J Clin Oncol. 2023 Apr 20;41(12):2166-2180. doi: 10.1200/JCO.22.00332. Epub 2022 Dec 6.
pmid
36473143
type
DERIVED
citation
Hwang M, Seiwert TY. Are taxanes the future for head and neck cancer? Pragmatism in the immunotherapy era. Lancet Oncol. 2021 Apr;22(4):413-415. doi: 10.1016/S1470-2045(21)00121-2. Epub 2021 Mar 5. No abstract available.
pmid
33684371
type
DERIVED