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