Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)
- Conditions
- Advanced Renal Cell CarcinomaMetastatic Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT02231749
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to compare the objective response rate, progression free survival and the overall survival of Nivolumab combined with Ipilimumab to Sunitinib monotherapy in patients with previously untreated Renal Cell Cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1390
-
Histological confirmation of renal cell carcinoma (RCC) with a clear-cell component
-
Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
-
No prior systemic therapy for RCC with the following exception:
-
One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
- Karnofsky Performance Status (KPS) of at least 70%
- Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Tumor tissue [formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition] must be received by the central vendor (block or unstained slides) in order to randomize a subject to study treatment. (Note: Fine Needle Aspiration [FNA] and bone metastases samples are not acceptable for submission)
-
- Any history of or current central nervous system (CNS) metastases. Baseline imaging of the brain is required within 28 days prior to randomization
- Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, Sunitinib, Pazopanib, Axitinib, Tivozanib, and Bevacizumab)
- Prior treatment with an anti-programmed death (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (>10 mg daily Prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
- Any condition requiring systemic treatment with corticosteroids (>10 mg daily Prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses >10 mg daily Prednisone equivalents are permitted in the absence of active autoimmune disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg Nivolumab Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends Arm B: Sunitinib 50 mg Ipilimumab Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks Arm A: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg Ipilimumab Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends Arm B: Sunitinib 50 mg Nivolumab Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks Arm B: Sunitinib 50 mg Sunitinib Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC) From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months) PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the IRRC (as per RECIST 1.1 criteria), or death due to any cause, whichever occurred first. Subsequent therapy included anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. Subjects who died without a reported progression were considered to have progressed on the date of their death.
Investigator-assessed Objective Response Rate(ORR) in Intermediate/Poor Risk Participants Per IRRC Using RECIST v1.1 From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months) ORR was defined as the proportion of randomized subjects who achieved a best response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria based on IRRC assessment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Overall Survival (OS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC) From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months) OS was defined as the time from randomization to the date of death from any cause. Survival time was censored at the date of last contact ("last known alive date") for subjects who were alive.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC) From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months) Overall survival is defined as the time from randomization to the date of death from any cause. For subjects that are alive, their survival time will be censored at the date of last contact ("last known alive date"). Overall survival will be censored for subjects at the date of randomization if they were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after subject's off-treatment date.
Progression-Free Survival (PFS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC) From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months) PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the IRRC (as per RECIST 1.1 criteria), or death due to any cause, whichever occurred first. Subsequent therapy included anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. Subjects who died without a reported progression were considered to have progressed on the date of their death.
Investigator-assessed Objective Response Rate(ORR) in Any Risk Participants Per IRRC Using RECIST v1.1 From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months) ORR was defined as the proportion of randomized subjects who achieved a best response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria based on IRRC assessment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Trial Locations
- Locations (189)
Local Institution - 0120
🇮🇱Haifa, Israel
Local Institution - 0057
🇺🇸La Jolla, California, United States
Local Institution - 0067
🇺🇸Stanford, California, United States
Local Institution - 0042
🇺🇸Iowa City, Iowa, United States
Local Institution - 0054
🇺🇸Allentown, Pennsylvania, United States
Local Institution - 0097
🇦🇷Caba, Argentina
Local Institution - 0138
🇺🇸New Haven, Connecticut, United States
Local Institution - 0035
🇺🇸Los Angeles, California, United States
Local Institution - 0005
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0001
🇺🇸New York, New York, United States
Local Institution - 0036
🇺🇸Buffalo, New York, United States
Local Institution - 0008
🇺🇸Charlotte, North Carolina, United States
Local Institution - 0163
🇺🇸Fairway, Kansas, United States
Local Institution - 0048
🇺🇸Baltimore, Maryland, United States
Local Institution - 0004
🇺🇸Baltimore, Maryland, United States
Local Institution - 0006
🇺🇸Duarte, California, United States
Local Institution - 0034
🇺🇸Washington, District of Columbia, United States
Local Institution - 0056
🇺🇸Dallas, Texas, United States
Local Institution - 0099
🇦🇷Berazategui, Buenos Aires, Argentina
Local Institution - 0075
🇦🇺Southport, Queensland, Australia
Local Institution - 0152
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Local Institution - 0161
🇺🇸Boston, Massachusetts, United States
Local Institution - 0170
🇫🇷Besançon, France
Local Institution - 0159
🇺🇸Chattanooga, Tennessee, United States
Local Institution - 0172
🇨🇦Toronto, Ontario, Canada
Local Institution - 0151
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Local Institution - 0007
🇺🇸Cleveland, Ohio, United States
Local Institution - 0156
🇧🇷Sao Paulo, Brazil
Local Institution - 0053
🇨🇿Brno, Czechia
Local Institution - 0070
🇦🇺Westmead, New South Wales, Australia
Local Institution - 0157
🇧🇷Rio de Janeiro, Brazil
Local Institution - 0123
🇩🇪Heidelberg, Germany
Local Institution - 0148
🇨🇦Toronto, Ontario, Canada
Local Institution - 0109
🇦🇹Wien, Austria
Local Institution - 0062
🇫🇷Bordeaux, France
Local Institution - 0169
🇫🇷La Roche-Sur-Yon Cedex 9, France
Local Institution - 0065
🇫🇷Strasbourg, France
Local Institution - 0058
🇫🇷Villejuif, France
Local Institution - 0073
🇦🇺Kogarah, New South Wales, Australia
Local Institution - 0052
🇨🇿Olomouc, Czechia
Local Institution - 0060
🇫🇷Marseille Cedex 9, France
Local Institution - 0108
🇦🇹Linz, Austria
Local Institution - 0076
🇦🇺Herston, Queensland, Australia
Local Institution - 0071
🇦🇺Clayton, Victoria, Australia
Local Institution - 0050
🇨🇿Liberec, Liberecký Kraj, Czechia
Local Institution - 0125
🇩🇪Aachen, Germany
Local Institution - 0143
🇩🇪Magdeburg, Germany
Local Institution - 0074
🇦🇺Murdoch, Australia
Local Institution - 0147
🇩🇪Hamburg, Germany
Local Institution - 0059
🇫🇷Toulouse Cedex 9, France
Local Institution - 0051
🇨🇿Hradec Kralove, Czechia
Local Institution - 0142
🇩🇪Hannover, Germany
Local Institution - 0127
🇩🇪Homburg, Germany
Local Institution - 0126
🇩🇪Erlangen, Germany
Local Institution - 0130
🇩🇪Ulm, Germany
Local Institution - 0015
🇮🇪Wilton, Cork, Ireland
Local Institution - 0088
🇪🇸Barcelona, Spain
Local Institution - 0141
🇩🇪Frankfurt, Germany
Local Institution - 0146
🇩🇪Muenster, Germany
Local Institution - 0129
🇩🇪Jena, Germany
Local Institution - 0086
🇪🇸Madrid, Spain
Local Institution - 0206
🇯🇵Kobe, Hyogo, Japan
Local Institution - 0175
🇲🇽Queretaro, Querétaro, Mexico
Local Institution - 0089
🇪🇸Barcelona, Spain
Local Institution - 0090
🇪🇸Sevilla, Spain
Local Institution - 0111
🇪🇸Oviedo, Spain
Local Institution - 0012
🇬🇧Swansea, United Kingdom
Local Institution - 0085
🇪🇸Madrid, Spain
Local Institution - 0087
🇪🇸Madrid, Spain
Local Institution - 0134
🇸🇪Solna, Sweden
Local Institution - 0009
🇬🇧Glasgow, Lanarkshire, United Kingdom
Local Institution - 0021
🇬🇧Manchester, United Kingdom
Local Institution - 0077
🇬🇧London, United Kingdom
Local Institution - 0176
🇰🇷Seoul, Korea, Republic of
Local Institution - 0135
🇺🇸Boston, Massachusetts, United States
Local Institution - 0041
🇺🇸Seattle, Washington, United States
Local Institution - 0044
🇺🇸Los Angeles, California, United States
Local Institution - 0068
🇺🇸Atlanta, Georgia, United States
Local Institution - 0038
🇺🇸Indianapolis, Indiana, United States
Local Institution - 0164
🇺🇸Columbus, Ohio, United States
Local Institution - 0031
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 0003
🇺🇸Houston, Texas, United States
Local Institution - 0032
🇺🇸Dallas, Texas, United States
Local Institution - 0140
🇦🇺Elizabeth Vale, South Australia, Australia
Local Institution - 0155
🇧🇷Sao Paulo, Brazil
Local Institution - 0162
🇨🇴Medellin, Colombia
Local Institution - 0063
🇫🇷Saint Herblain, France
Local Institution - 0124
🇩🇪Muenchen, Germany
Local Institution - 0184
🇭🇺Gyula, Békés, Hungary
Local Institution - 0121
🇮🇱Petach Tikva, Israel
Local Institution - 0187
🇯🇵Chiba-shi, Chiba, Japan
Local Institution - 0183
🇯🇵Sapporo-shi, Hokkaido, Japan
Local Institution - 0205
🇯🇵Tsukuba-shi, Ibaraki, Japan
Local Institution - 0186
🇯🇵Yokohama-shi, Kanagawa, Japan
Local Institution - 0191
🇯🇵Kyoto-shi, Kyoto, Japan
Local Institution - 0194
🇯🇵Tokushima-shi, Tokushima, Japan
Local Institution - 0197
🇯🇵Bunkyo-ku, Tokyo, Japan
Local Institution - 0207
🇯🇵Koto-ku, Tokyo, Japan
Local Institution - 0193
🇯🇵Shinjuku-ku, Tokyo, Japan
Local Institution - 0178
🇰🇷Seoul, Korea, Republic of
Local Institution - 0203
🇯🇵Yamagata, Japan
Local Institution - 0177
🇰🇷Seoul, Korea, Republic of
Local Institution - 0010
🇬🇧London, Greater London, United Kingdom
Local Institution - 0150
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Local Institution - 0061
🇫🇷Paris, Île-de-France, France
Local Institution - 0018
🇮🇪Dublin 7, Dublin, Ireland
Local Institution - 0104
🇦🇺Nedlands, Western Australia, Australia
Local Institution - 0017
🇮🇪Dublin 7, Dublin, Ireland
Local Institution - 0043
🇺🇸Detroit, Michigan, United States
Local Institution - 0045
🇺🇸Durham, North Carolina, United States
Local Institution - 0066
🇺🇸Nashville, Tennessee, United States
Local Institution - 0136
🇩🇰Aarhus N, Denmark
Local Institution - 0158
🇩🇰Herlev, Denmark
Local Institution - 0137
🇩🇰Odense, Denmark
Local Institution - 0022
🇮🇹Arezzo, Italy
Local Institution - 0024
🇮🇹Meldola (fc), Italy
Local Institution - 0023
🇮🇹Milano, Italy
Local Institution - 0064
🇮🇹Napoli, Italy
Local Institution - 0026
🇮🇹Roma, Italy
Local Institution - 0079
🇮🇹Padova, Italy
Local Institution - 0025
🇮🇹Pavia, Italy
Local Institution - 0055
🇺🇸Charleston, South Carolina, United States
Local Institution - 0139
🇦🇷Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina
Local Institution - 0081
🇨🇴Medellin, Colombia
Local Institution - 0192
🇯🇵Akita-shi, Akita, Japan
Local Institution - 0204
🇯🇵Okayama-shi, Okayama, Japan
Local Institution - 0029
🇳🇱Amsterdam, Netherlands
Local Institution - 0040
🇳🇱Groningen, Netherlands
Local Institution - 0093
🇵🇱Krakow, Poland
Local Institution - 0122
🇹🇷Istanbul, Turkey
Local Institution - 0149
🇨🇦Calgary, Alberta, Canada
Local Institution - 0110
🇺🇸Boston, Massachusetts, United States
Local Institution - 0095
🇦🇷San Miguel De Tucuman, Tucuman, Argentina
Local Institution - 0096
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Local Institution - 0020
🇧🇪Gent, Belgium
Local Institution - 0072
🇦🇺Box Hill, Victoria, Australia
Local Institution - 0173
🇺🇸Boston, Massachusetts, United States
Local Institution - 0019
🇧🇪Leuven, Belgium
Local Institution - 0080
🇨🇴Bogota, Colombia
Local Institution - 0016
🇮🇪Dublin, Ireland
Local Institution - 0182
🇨🇦Kelowna, British Columbia, Canada
Local Institution - 0100
🇦🇷Cordoba, Argentina
Local Institution - 0101
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0103
🇨🇱Vina del Mar, Chile
Local Institution - 0084
🇭🇺Pecs, Hungary
Local Institution - 0196
🇯🇵Fukuoka-shi, Fukuoka, Japan
Local Institution - 0133
🇨🇦Edmonton, Alberta, Canada
Local Institution - 0098
🇦🇷Capital Federal, Buenos Aires, Argentina
Local Institution - 0027
🇫🇮Helsinki, Uusimaa, Finland
Local Institution - 0107
🇦🇹Wels, Austria
Local Institution - 0102
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0144
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0028
🇫🇮Tampere, Finland
Local Institution - 0117
🇮🇱Kfar Saba, Israel
Local Institution - 0119
🇮🇱Zerifin, Israel
Local Institution - 0132
🇨🇦Montreal, Quebec, Canada
Local Institution - 0131
🇨🇦Moncton, New Brunswick, Canada
Local Institution - 0082
🇭🇺Debrecen, Hungary
Local Institution - 0118
🇮🇱Ramat-gan, Israel
Local Institution - 0190
🇯🇵Osaka-sayama, Osaka, Japan
Local Institution - 0201
🇯🇵Suita-shi, Osaka, Japan
Local Institution - 0195
🇯🇵Bunkyo-ku, Tokyo, Japan
Local Institution - 0198
🇯🇵Tokyo, Japan
Local Institution - 0167
🇲🇽Oaxaca, Mexico
Local Institution - 0114
🇹🇷Antalya, Turkey
Local Institution - 0153
🇧🇷Sao Paulo, São Paulo, Brazil
Local Institution - 0083
🇭🇺Budapest, Hungary
Local Institution - 0180
🇨🇳Taipei, Taiwan
Local Institution - 0209
🇯🇵Hirosaki-shi, Aomori, Japan
Local Institution - 0200
🇯🇵Morioka-shi, Iwate, Japan
Local Institution - 0189
🇯🇵Kumamoto-shi, Kumamoto, Japan
Local Institution - 0199
🇯🇵Niigata-shi, Niigata, Japan
Local Institution - 0168
🇲🇽Mexico D.f., Distrito Federal, Mexico
Local Institution - 0030
🇳🇱Nijmegen, Netherlands
Local Institution - 0106
🇵🇱Wroclaw, Poland
Local Institution - 0188
🇯🇵Sapporo-shi, Hokai-do, Japan
Local Institution - 0208
🇯🇵Hamamatsu-shi, Shizuoka, Japan
Local Institution - 0202
🇯🇵Bunkyo-ku, Tokyo, Japan
Local Institution - 0115
🇹🇷Ankara, Turkey
Local Institution - 0185
🇯🇵Shinjuku-Ku, Tokyo, Japan
Local Institution - 0171
🇲🇽Monterrey, Nuevo Leon, Mexico
Local Institution - 0112
🇵🇱Poznan, Poland
Local Institution - 0181
🇨🇳Taoyuan, Taiwan
Local Institution - 0179
🇨🇳Taipei, Taiwan
Local Institution - 0011
🇬🇧Northwood, United Kingdom
Local Institution - 0049
🇺🇸Tampa, Florida, United States
Local Institution - 0046
🇺🇸Ann Arbor, Michigan, United States
Local Institution - 0039
🇺🇸Portland, Oregon, United States
Local Institution - 0128
🇨🇦Vancouver, British Columbia, Canada