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

Head and Neck Cancer Clinical Trial

— CheckMate 651  

Official title:

An Open Label, Randomized, Two Arm Phase III Study of Nivolumab in Combination With Ipilimumab Versus Extreme Study Regimen (Cetuximab + Cisplatin/Carboplatin + Fluorouracil) as First Line Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02741570
• Other study ID #: CA209-651
• Secondary ID: 2016-000725-39
• Status: Completed
• Phase: Phase 3
• Start date: October 5, 2016
• Est. completion date: September 22, 2022

Study information

• Verified date: August 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 947
• Est. completion date: September 22, 2022
• Est. primary completion date: May 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

Biological:
• Nivolumab

• Ipilimumab

Drug:
• Cetuximab/Erbitux

• Cisplatin/Platinol

• Carboplatin/Paraplatin

• Fluorouracil/Adrucil

Locations

Country	Name	City	State
Australia	Local Institution - 0142	Blacktown	New South Wales
Australia	Local Institution - 0077	Brisbane	Queensland
Australia	Local Institution - 0022	Clayton	Victoria
Australia	Local Institution - 0127	Darlinghurst	New South Wales
Australia	Local Institution - 0036	Douglas	Queensland
Australia	Local Institution - 0021	Elizabeth Vale	South Australia
Australia	Local Institution - 0128	Gosford	New South Wales
Australia	Local Institution - 0131	Melbourne	Victoria
Australia	Local Institution - 0020	Nedlands	Western Australia
Australia	Local Institution - 0019	St. Leonards	New South Wales
Austria	Local Institution - 0075	Linz
Austria	Local Institution - 0071	Wien
Brazil	Local Institution - 0117	Barretos	Sao Paulo
Brazil	Local Institution - 0148	Belo Horizonte	Minas Gerais
Brazil	Local Institution - 0121	Ijui	RIO Grande DO SUL
Brazil	Local Institution - 0120	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0122	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0123	Sao Jose De Rio Preto	Sao Paulo
Brazil	Local Institution - 0118	Sao Paulo
Brazil	Local Institution - 0124	Sao Paulo
France	Local Institution - 0133	Amiens	Somme
France	Local Institution - 0094	Bordeaux
France	Local Institution - 0140	La Tronche
France	Local Institution - 0090	Lille
France	Local Institution - 0054	Lyon
France	Local Institution - 0138	Lyon
France	Local Institution - 0126	Marseille
France	Local Institution - 0055	Nice Cedex 2
France	Local Institution	Paris
France	Local Institution - 0039	Paris
France	Local Institution - 0088	Paris
France	Local Institution - 0089	Strasbourg
France	Local Institution - 0040	Villejuif Cedex
Germany	Local Institution - 0068	Bonn
Germany	Local Institution - 0078	Freiburg
Germany	Local Institution - 0067	Hamburg
Germany	Local Institution - 0092	Hannover
Germany	Local Institution - 0079	Heidelberg
Germany	Local Institution - 0074	Leipzig
Germany	Local Institution - 0070	Mainz
Germany	Local Institution - 0065	Muenchen
Germany	Local Institution - 0069	Ulm
Germany	Local Institution - 0066	Wuerzburg
Greece	Local Institution - 0018	Athens
Greece	Local Institution - 0017	Nea Kifissia
Greece	Local Institution - 0051	Thessaloniki
Ireland	Local Institution - 0147	Dublin 8	Dublin
Israel	Local Institution - 0062	Haifa
Israel	Local Institution - 0060	Jerusalem
Israel	Local Institution - 0063	Petah-tikva
Israel	Local Institution - 0061	Ramat-gan
Israel	Local Institution - 0064	Tel-Aviv
Italy	Local Institution - 0044	Cuneo
Italy	IRST Meldola	Meldola (fc)
Italy	Local Institution - 0042	Milano	MI
Italy	Azienda Ospedaliera Universitaria Di Modena	Modena
Italy	Aorn Dei Colli	Napoli
Italy	Istituto Nazionale Tumori Fondazione Pascale	Napoli
Italy	Azienda Ospedaliera Di Perugia	Perugia
Italy	Fondazione Policlinico Universitario A. Gemelli	Roma
Italy	Local Institution - 0043	Torino	TO
Japan	Local Institution - 0107	Akashi-shi	Hyogo
Japan	Local Institution - 0153	Bunkyo-ku	Tokyo
Japan	Local Institution - 0101	Chuo-ku	Tokyo
Japan	Local Institution - 0113	Fukuoka-shi	Fukuoka
Japan	Local Institution - 0152	Isehara	Kanagawa
Japan	Local Institution - 0100	Kashiwa	Chiba
Japan	Local Institution - 0109	Kita-gun
Japan	Local Institution - 0149	Kitaadachi-gun	Saitama
Japan	Local Institution - 0102	Kobe-shi	Hyogo
Japan	Local Institution - 0104	Koto-ku	Tokyo
Japan	Local Institution - 0106	Nagoya	Aichi
Japan	Local Institution - 0151	Natori-shi	Miyagi
Japan	Local Institution - 0146	Osakasayaha	Osaka
Japan	Local Institution - 0105	Sapporo-shi	Hokkaido
Japan	Local Institution - 0108	Sendai-shi	Miyagi
Japan	Local Institution	Shimotsuke-shi	Tochigi
Japan	Local Institution - 0114	Sunto-gun	Shizuoka
Japan	Local Institution - 0099	Takatsuki-shi	Osaka
Japan	Local Institution - 0150	Yokohama-shi	Kanagawa
Korea, Republic of	Local Institution - 0096	Gangnam-gu
Korea, Republic of	Local Institution - 0095	Seoul
Korea, Republic of	Local Institution - 0110	Seoul
Mexico	Local Institution - 0032	Leon de los Aldama	Guanajuato
Mexico	Local Institution - 0030	Mexico	Distrito Federal
Mexico	Local Institution - 0034	Mexico City	Distrito Federal
Mexico	Local Institution - 0033	Monterrey	Nuevo LEON
Mexico	Local Institution - 0031	Morelia	Michoacan
Mexico	Local Institution - 0035	Oaxaca
Poland	Local Institution - 0037	Bydgoszcz
Poland	Local Institution - 0023	Gdansk
Poland	Local Institution - 0129	Gliwice
Poland	Local Institution - 0026	Krakow
Poland	Local Institution - 0025	Warszawa
Spain	Local Institution - 0083	Barcelona
Spain	Local Institution - 0130	L'Hospitalet Del Llobregat
Spain	Local Institution - 0082	Madrid
Spain	Local Institution - 0085	Madrid
Spain	Local Institution - 0084	Sevilla
Spain	Local Institution - 0081	Valencia
Switzerland	Local Institution - 0072	Basel
Switzerland	Local Institution - 0073	Zuerich
Taiwan	Local Institution - 0097	Taichung
Taiwan	Local Institution - 0098	Taipei
United Kingdom	Local Institution - 0050	Birmingham	West Midlands
United Kingdom	Local Institution - 0045	London	Greater London
United Kingdom	Local Institution - 0046	Manchester	Greater Manchester
United Kingdom	Local Institution - 0049	Newcastle Upon Tyne	Durham
United Kingdom	Local Institution - 0132	Sheffield
United Kingdom	Local Institution - 0047	Southampton	Hampshire
United Kingdom	Local Institution - 0091	Sutton	Surrey
United States	Local Institution - 0004	Ann Arbor	Michigan
United States	Local Institution - 0111	Atlanta	Georgia
United States	Local Institution - 0001	Boston	Massachusetts
United States	Local Institution - 0080	Boston	Massachusetts
United States	Local Institution - 0093	Boston	Massachusetts
United States	Local Institution - 0012	Charlotte	North Carolina
United States	Local Institution - 0003	Charlottesville	Virginia
United States	Local Institution - 0006	Chicago	Illinois
United States	Local Institution - 0007	Columbus	Ohio
United States	Local Institution - 0139	Dallas	Texas
United States	Local Institution - 0135	Duarte	California
United States	Local Institution - 0011	Fairfax	Virginia
United States	Local Institution - 0009	Houston	Texas
United States	Local Institution - 0014	Houston	Texas
United States	Local Institution - 0028	Jacksonville	Florida
United States	Local Institution - 0010	Langhorne	Pennsylvania
United States	Local Institution - 0125	Morgantown	West Virginia
United States	Local Institution - 0015	Philadelphia	Pennsylvania
United States	Local Institution - 0013	Pittsburgh	Pennsylvania
United States	Local Institution - 0005	Stanford	California
United States	Local Institution - 0008	Tampa	Florida
United States	Local Institution - 0134	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  France,  Germany,  Greece,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) =20	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)	From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)
Primary	Overall Survival (OS) in All Randomized Participants	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)	From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)
Secondary	Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) = 1	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)	From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)
Secondary	Progression Free Survival (PFS)	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).	From randomization to disease progression or death (Up to approximately 65 months)
Secondary	Objective Response Rate (ORR)	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.	From randomization up to approximately 65 months
Secondary	Duration of Objective Response (DOR)	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.	From randomization to the first documented response (CR or PR) and progression (up to approximately 65 months)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls