A Study Comparing Nivolumab, Nivolumab in Combination With Ipilimumab and Placebo in Participants With Localized Kidney Cancer Who Underwent Surgery to Remove Part of a Kidney
- Conditions
- Carcinoma, Renal Cell
- Interventions
- Registration Number
- NCT03138512
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine whether nivolmab alone or the combination of nivolumab and ipilimumab versus placebo, is safe and effective for delaying or preventing recurrence of cancer in participants who have experienced partial or entire removal of a kidney.
- Detailed Description
The study has two primary endpoints. The first primary completion date is anticipated to be reached July 2022 (DFS in Part A). The second primary completion date is anticipated to be reached July 2024 (DFS in Part B).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1641
- Kidney tumor has been completely resected with negative surgical margins obtained. The randomization must occur greater than 4 weeks and less than (or equal to) 12 weeks from the date of nephrectomy
- Pathologic tumor, node, and metastasis (TNM) staging meeting one of the following: pT2a, G3 or G4, N0 M0; pT2b, G any, N0 M0; pT3, (a, b, c), G any, N0 M0; pT4, G any, N0 M0; pT any, G any, N1 M0
- Post-nephrectomy tumor shows renal cell cancer (RCC) with a predominantly clear cell histology, including participants with sarcomatoid features
- Participants must have no clinical or radiological evidence of macroscopic residual disease or distant metastases after nephrectomy
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
- Women must agree to follow methods of contraception, if applicable
- Participants with an active known or suspected autoimmune disease
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- Any severe or serious, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation
- History of allergy or hypersensitivity to study drug components
- Participants with a condition requiring systemic treatment with corticosteroids
- Participants who have received a live/attenuated vaccine within 30 days of first treatment
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B, Arm B: nivolumab placebo + ipilimumab placebo nivolumab placebo - Part B, Arm B: nivolumab placebo + ipilimumab placebo ipilimumab placebo - Part A, Arm B: nivolumab placebo + ipilimumab placebo ipilimumab placebo - Part B, Arm C: nivolumab + ipilimumab placebo ipilimumab placebo - Part B, Arm A: nivolumab + ipilimumab nivolumab - Part A, Arm A: nivolumab + ipilimumab nivolumab - Part A, Arm B: nivolumab placebo + ipilimumab placebo nivolumab placebo - Part A, Arm A: nivolumab + ipilimumab ipilimumab - Part B, Arm A: nivolumab + ipilimumab ipilimumab - Part B, Arm C: nivolumab + ipilimumab placebo nivolumab -
- Primary Outcome Measures
Name Time Method Disease-Free Survival (DFS) by BICR - Treatment Part A and B From randomization to development of local disease recurrence, distance metastasis, or death, whichever came first (up to approximately 72 months) Disease-Free Survival (DFS) is defined as the time from randomization to development of local disease recurrence (ie, recurrence of primary tumor in situ or occurrence of a secondary renal cell carcinoma (RCC) primary cancer), distance metastasis, or death, whichever came first per Blinded Independent Central Review (BICR) based on Kaplan-Meier estimates.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) - Treatment Part A and B From randomization to the date of death (up to approximately 72 months) Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the participants was known to be alive. Based on Kaplan-Meier estimates.
Overall Survival (OS) Rate (5 Years) - Treatment Part A and B At 5 years Overall survival rate at 5 years is defined as the percentage of participants who are alive at 5 years.
Disease-Free Survival (DFS) Per BICR in Contemporaneously Randomized Combination and Monotherapy Participants - Treatment Part B From randomization to development of local disease recurrence, distance metastasis, or death, whichever came first (up to approximately 72 months) Disease-Free Survival (DFS) is defined as the time from randomization to development of local disease recurrence (ie, recurrence of primary tumor in situ or occurrence of a secondary renal cell carcinoma (RCC) primary cancer), distance metastasis, or death, whichever came first per Blinded Independent Central Review (BICR) based on Kaplan-Meier estimates.
Overall Survival (OS) in the Contemporaneously Randomized Combination and Monotherapy Participants - Treatment Part B From randomization to the date of death (up to approximately 72 months) Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the participants was known to be alive. Based on Kaplan-Meier estimates
The Number of Participants With Adverse Events up to 30 Days After Last Dose of Study Therapy - Treatment Part A From first dose to 30 days post last dose (up to approximately 40 weeks) An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
The Number of Participants With Adverse Events up to 30 Days After Last Dose of Study Therapy - Treatment Part B From first dose to 30 days post last dose (up to approximately 40 weeks) An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
The Number of Participants With Adverse Events up to 100 Days After Last Dose of Study Therapy - Treatment Part A From first dose to 100 days post last dose (up to approximately 50 weeks) An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
The Number of Participants With Adverse Events up to 100 Days After Last Dose of Study Therapy - Treatment Part B From first dose to 100 days post last dose (up to approximately 50 weeks) An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Graded according to NCI CTCAE (Version 4) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
The Number of Participants Experiencing Laboratory Parameters by Worst CTC (Grade 3-4) That Worsened Relative to Baseline up to 30 Days - Treatment Part A From first dose to 30 days post last dose (up to approximately 40 weeks) Graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE, Version 4.0\] where grade 3 = severe, and grade 4 = life-threatening. Baseline evaluations are defined as evaluations or events that occur before the date and time of the first dose of study treatment.
The Number of Participants Experiencing Laboratory Parameters by Worst CTC (Grade 3-4) That Worsened Relative to Baseline up to 30 Days - Treatment Part B From first dose to 30 days post last dose (up to approximately 40 weeks) Graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE, Version 4.0\] where grade 3 = severe, and grade 4 = life-threatening. Baseline evaluations are defined as evaluations or events that occur before the date and time of the first dose of study treatment.
The Number of Participants Experiencing Laboratory Parameters by Worst CTC (Grade 3-4) That Worsened Relative to Baseline up to 100 Days - Treatment Part A From first dose to 100 days post last dose (up to approximately 50 weeks) Graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE, Version 4.0\] where grade 3 = severe, and grade 4 = life-threatening. Baseline evaluations are defined as evaluations or events that occur before the date and time of the first dose of study treatment.
The Number of Participants Experiencing Laboratory Parameters by Worst CTC (Grade 3-4) That Worsened Relative to Baseline up to 100 Days - Treatment Part B From first dose to 100 days post last dose (up to approximately 50 weeks) Graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE, Version 4.0\] where grade 3 = severe, and grade 4 = life-threatening. Baseline evaluations are defined as evaluations or events that occur before the date and time of the first dose of study treatment.
Trial Locations
- Locations (198)
Local Institution - 0019
🇺🇸Birmingham, Alabama, United States
Local Institution - 0056
🇺🇸Springdale, Arkansas, United States
Local Institution - 0186
🇺🇸Los Angeles, California, United States
Local Institution - 0180
🇺🇸Los Angeles, California, United States
Local Institution - 0002
🇺🇸San Francisco, California, United States
Local Institution - 0185
🇺🇸Aurora, Colorado, United States
Local Institution - 0016
🇺🇸Athens, Georgia, United States
Local Institution - 0005
🇺🇸Chicago, Illinois, United States
Local Institution
🇹🇷Istanbul, Turkey
Local Institution - 0007
🇺🇸Buffalo, New York, United States
Local Institution - 0006
🇺🇸Saint Louis, Missouri, United States
Local Institution - 0012
🇺🇸Howell, New Jersey, United States
Local Institution - 0181
🇺🇸New York, New York, United States
Local Institution - 0001
🇺🇸New York, New York, United States
Local Institution - 0008
🇺🇸Columbus, Ohio, United States
Local Institution - 0009
🇺🇸Portland, Oregon, United States
Local Institution - 0010
🇺🇸Allentown, Pennsylvania, United States
Local Institution - 0014
🇺🇸Greenville, South Carolina, United States
Local Institution - 0013
🇺🇸Chattanooga, Tennessee, United States
Local Institution - 0183
🇺🇸Nashville, Tennessee, United States
Local Institution - 0057
🇺🇸Fairfax, Virginia, United States
Local Institution - 0178
🇦🇷Capital Federal, Buenos Aires, Argentina
Local Institution - 0126
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Local Institution - 0203
🇦🇷Ciudad Autónoma De Buenos Aires, Buenos Aires, Argentina
Local Institution - 0095
🇦🇷Mar Del Plata, Buenos Aires, Argentina
Local Institution - 0208
🇦🇷Mar Del Plata, Buenos Aires, Argentina
Local Institution - 0173
🇦🇷Rio Cuarto, Cordoba, Argentina
Local Institution - 0232
🇦🇷Bariloche, RIO Negro, Argentina
Local Institution - 0096
🇦🇷Cordoba, Argentina
Local Institution - 0179
🇦🇷Buenos Aires, Argentina
Local Institution - 0099
🇦🇷Caba, Argentina
Local Institution - 0098
🇦🇷Cordoba, Argentina
Local Institution - 0164
🇦🇷San Juan, Argentina
Local Institution - 0097
🇦🇷Tucuman, Argentina
Local Institution - 0215
🇦🇺Macquarie Park, New South Wales, Australia
Local Institution - 0032
🇦🇺Northmead, New South Wales, Australia
Local Institution - 0035
🇦🇺St Leonards, New South Wales, Australia
Local Institution - 0113
🇦🇺South Brisbane, Queensland, Australia
Local Institution - 0213
🇦🇺Southport, Queensland, Australia
Local Institution - 0036
🇦🇺Randwick, New South Wales, Australia
Local Institution - 0034
🇦🇺Elizabeth Vale, South Australia, Australia
Local Institution - 0033
🇦🇺Clayton, Victoria, Australia
Local Institution - 0214
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0031
🇦🇺Murdoch, Western Australia, Australia
Local Institution - 0068
🇦🇹Linz, Austria
Local Institution - 0084
🇦🇹Wien, Austria
Local Institution - 0058
🇧🇪Gent, Oost-Vlaanderen, Belgium
Local Institution - 0064
🇧🇪Anderlecht, Belgium
Local Institution - 0060
🇧🇪Hasselt, Belgium
Local Institution - 0059
🇧🇪Liege, Belgium
Local Institution - 0047
🇧🇷Brasilia, Distrito Federal, Brazil
Local Institution - 0045
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Local Institution - 0046
🇧🇷Ijui, RIO Grande DO SUL, Brazil
Local Institution - 0050
🇧🇷Sao Paulo, Brazil
Local Institution - 0041
🇨🇦Vancouver, British Columbia, Canada
Local Institution - 0086
🇨🇦Saint John, New Brunswick, Canada
Local Institution - 0048
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Local Institution - 0043
🇧🇷Barretos, Sao Paulo, Brazil
Local Institution - 0044
🇧🇷São Paulo, SAO Paulo, Brazil
Local Institution - 0160
🇧🇷Rio de Janeiro, Brazil
Local Institution - 0087
🇨🇦Oshawa, Ontario, Canada
Local Institution - 0112
🇨🇦Toronto, Ontario, Canada
Local Institution - 0042
🇨🇦Montreal, Quebec, Canada
Local Institution - 0221
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0222
🇨🇱Vina del Mar, Valparaiso, Chile
Local Institution - 0147
🇨🇳Beijing, Beijing, China
Local Institution - 0040
🇨🇦Rimouski, Quebec, Canada
Local Institution - 0223
🇨🇱La Serena, Coquimbo, Chile
Local Institution - 0246
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0153
🇨🇳Beijing, Beijing, China
Local Institution - 0159
🇨🇳Beijing, Beijing, China
Local Institution - 0132
🇨🇳Fuzhou, Fujian, China
Local Institution - 0141
🇨🇳Guangzhou, Guangdong, China
Local Institution - 0194
🇨🇳Wuhan, Hebei, China
Local Institution - 0133
🇨🇳Wuhan, Hubei, China
Local Institution - 0138
🇨🇳Nanjing, Jiangsu, China
Local Institution - 0140
🇨🇳Nanchang, Jiangxi, China
Local Institution - 0145
🇨🇳Changchun, Jilin, China
Local Institution - 0146
🇨🇳Yantai, Shandong, China
Local Institution - 0137
🇨🇳Shanghai, Shanghai, China
Local Institution - 0144
🇨🇳Xi'an, Shan3xi, China
Local Institution - 0166
🇨🇳Shanghai, Shanghai, China
Local Institution - 0152
🇨🇳Shanghai, Shanghai, China
Local Institution - 0148
🇨🇳Shanghai, Shanghai, China
Local Institution - 0142
🇨🇳Chengdu, Sichuan, China
Local Institution - 0143
🇨🇳Chengdu, Sichuan, China
Local Institution - 0175
🇨🇳Tianjin, Tianjin, China
Local Institution - 0157
🇨🇳Hangzhou, Zhejiang, China
Local Institution - 0131
🇨🇳Hangzhou, Zhejiang, China
Local Institution - 0134
🇨🇳Guangzhou, China
Local Institution - 0139
🇨🇳Nanjing, China
Local Institution - 0176
🇨🇳Shanghai, China
Local Institution - 0227
🇨🇴Medellin, Antioquia, Colombia
Local Institution - 0228
🇨🇴Valledupar, Cesar, Colombia
Local Institution - 0229
🇨🇴Bogotá, Colombia
Local Institution - 0230
🇨🇴Floridablanca, Colombia
Local Institution - 0226
🇨🇴Pereira, Colombia
Local Institution - 0080
🇫🇷Bordeaux, France
Local Institution - 0082
🇫🇷La Roche-Sur-Yon Cedex 9, France
Local Institution - 0094
🇨🇿Hradec Kralove, Czechia
Local Institution - 0025
🇨🇿Olomouc, Czechia
Local Institution - 0083
🇫🇷Besançon Cedex, France
Local Institution - 0116
🇫🇷Lyon Cedex 08, France
Local Institution - 0079
🇫🇷Marseille Cedex 9, France
Local Institution - 0198
🇫🇷Paris, France
Local Institution - 0081
🇫🇷Rennes, France
Local Institution - 0077
🇫🇷Strasbourg, France
Local Institution - 0115
🇫🇷Toulouse Cedex 9, France
Local Institution - 0150
🇫🇷Tours Cedex, France
Local Institution - 0078
🇫🇷Vandoeuvre Les Nancy, France
Local Institution - 0076
🇫🇷Villejuif, France
Local Institution - 0217
🇩🇪Tubingen, Baden-Württemberg, Germany
Local Institution - 0053
🇩🇪Aachen, Germany
Local Institution - 0103
🇩🇪Essen, Germany
Local Institution - 0052
🇩🇪Hamburg, Germany
Local Institution - 0055
🇩🇪Rostock, Germany
Local Institution - 0231
🇩🇪Hannover, Germany
Local Institution - 0061
🇩🇪Hannover, Germany
Local Institution - 0062
🇩🇪Jena, Germany
Local Institution - 0102
🇩🇪Munich, Germany
Local Institution - 0054
🇩🇪Nuernberg, Germany
Local Institution - 0101
🇩🇪Wuerzburg, Germany
Local Institution - 0105
🇮🇹Arezzo, Italy
Local Institution - 0172
🇮🇹Cremona, Italy
Local Institution - 0106
🇮🇹Napoli, Italy
Local Institution - 0107
🇮🇹Parma, Italy
Local Institution - 0109
🇮🇹Roma, Italy
Local Institution - 0108
🇮🇹Verona, Italy
Local Institution - 0129
🇯🇵Toyoake Shi, Aichi, Japan
Local Institution - 0193
🇯🇵Hirosaki-shi, Aomori, Japan
Local Institution - 0158
🇯🇵Chiba-shi, Chiba, Japan
Local Institution - 0121
🇯🇵Fukuoka-shi, Fukuoka, Japan
Local Institution - 0156
🇯🇵Sapporo-shi, Hokkaido, Japan
Local Institution - 0167
🇯🇵Kobe-shi, Hyogo, Japan
Local Institution - 0191
🇯🇵Tsukuba-shi, Ibaraki, Japan
Local Institution - 0168
🇯🇵Shiwa-gun, Iwate, Japan
Local Institution - 0128
🇯🇵Yokohama-shi, Kanagawa, Japan
Local Institution - 0216
🇯🇵Kumamoto-shi, Kumamoto, Japan
Local Institution - 0130
🇯🇵Kamigyo-ku, Kyoto, Japan
Local Institution - 0123
🇯🇵Nagasaki-shi, Nagasaki, Japan
Local Institution - 0120
🇯🇵Niigata-shi, Niigata, Japan
Local Institution - 0125
🇯🇵Osakasayama-shi, Osaka, Japan
Local Institution - 0122
🇯🇵Suita-shi, Osaka, Japan
Local Institution - 0162
🇯🇵Tokushima-shi, Tokushima, Japan
Local Institution - 0188
🇯🇵Adachi-ku, Tokyo, Japan
Local Institution - 0189
🇯🇵Bunkyo-ku, Tokyo, Japan
Local Institution - 0119
🇯🇵Bunkyo-ku, Tokyo, Japan
Local Institution - 0149
🇯🇵Shinjuku-ku, Tokyo, Japan
Local Institution - 0163
🇯🇵Ube-shi, Yamaguchi, Japan
Local Institution - 0165
🇯🇵Hiroshima, Japan
Local Institution - 0192
🇯🇵Wakayama, Japan
Local Institution - 0127
🇯🇵Yamagata, Japan
Local Institution - 0242
🇲🇽Tijuana, BAJA California, Mexico
Local Institution - 0197
🇲🇽Tuxtla Gutierrez, Chiapas, Mexico
Local Institution - 0195
🇲🇽Torreón, Coahuila, Mexico
Local Institution - 0151
🇲🇽Ciudad de Mexico, Distrito Federal, Mexico
Local Institution - 0111
🇲🇽Tlalpan, Distrito Federal, Mexico
Local Institution - 0104
🇲🇽Mazatlan, Sinaloa, Mexico
Local Institution - 0110
🇲🇽Zapopan, Jalisco, Mexico
Local Institution - 0196
🇲🇽Merida, Yucatan, Mexico
Local Institution - 0089
🇲🇽Chihuahua, Mexico
Local Institution - 0088
🇲🇽Monterrey, NL, Mexico
Local Institution - 0169
🇲🇽San Luis Potosi, Mexico
Local Institution - 0066
🇳🇱Amsterdam, Netherlands
Local Institution - 0067
🇳🇱Rotterdam, Netherlands
Local Institution - 0092
🇳🇱Zwolle, Netherlands
Local Institution - 0155
🇵🇱Bydgoszcz, Poland
Local Institution - 0038
🇵🇱Wroclaw, Poland
Local Institution - 0243
🇷🇴Bucharest, Romania
Local Institution - 0200
🇷🇴Cluj-Napoca, Romania
Local Institution - 0247
🇷🇴Cluj, Romania
Local Institution - 0199
🇷🇴Craiova, Romania
Local Institution - 0202
🇷🇴Iași, Romania
Local Institution - 0065
🇷🇺Moscow, Russian Federation
Local Institution - 0170
🇷🇺Novosibirsk, Russian Federation
Local Institution - 0171
🇷🇺Saint-Petersburg, Russian Federation
Local Institution - 0021
🇷🇺Saint-Petersburg, Russian Federation
Local Institution - 0018
🇸🇬Singapore, Central Singapore, Singapore
Local Institution - 0017
🇸🇬Singapore, Singapore
Local Institution - 0204
🇪🇸Barcelona, Spain
Local Institution - 0206
🇪🇸Barcelona, Spain
Local Institution - 0124
🇪🇸Caceres, Spain
Local Institution - 0207
🇪🇸Cordoba, Spain
Local Institution - 0118
🇪🇸Lugo, Spain
Local Institution - 0114
🇪🇸Madrid, Spain
Local Institution - 0205
🇪🇸Madrid, Spain
Local Institution - 0117
🇪🇸Sabadell, Spain
Local Institution - 0161
🇪🇸Sevilla, Spain
Local Institution - 0218
🇨🇭Chur, Switzerland
Local Institution - 0219
🇨🇭Sankt Gallen, Switzerland
Local Institution - 0225
🇨🇭Zuerich, Switzerland
Local Institution - 0209
🇹🇷Ankara, Turkey
Local Institution - 0210
🇹🇷Istanbul, Turkey
Local Institution - 0075
🇬🇧Southampton, Hampshire, United Kingdom
Local Institution - 0063
🇬🇧Manchester, United Kingdom
Local Institution - 0071
🇬🇧Northwood, United Kingdom
Local Institution - 0073
🇬🇧Preston, United Kingdom
Local Institution - 0072
🇬🇧Swansea, United Kingdom