Clinical trial NCT03138512: 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
Official title: A Phase 3 Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab vs Placebo in Participants With Localized Renal Cell Carcinoma Who Underwent Radical or Partial Nephrectomy and Who Are at High Risk of Relapse
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Renal Cell
Keywords: localized
resected
adjuvant
Renal Cell Carcinoma
Kidney Cancer
Nephrectomy
Clear cell
High Risk of Relapse/Recurrence
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-05-03
Enrollment: 1641
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Disease-Free Survival (DFS) by BICR - Treatment Part A and B
timeFrame: From randomization to development of local disease recurrence, distance metastasis, or death, whichever came first (up to approximately 72 months)
Secondary outcomes:
measure: Overall Survival (OS) - Treatment Part A and B
timeFrame: From randomization to the date of death (up to approximately 72 months)
measure: Overall Survival (OS) Rate (5 Years) - Treatment Part A and B
timeFrame: At 5 years
measure: Disease-Free Survival (DFS) Per BICR in Contemporaneously Randomized Combination and Monotherapy Participants - Treatment Part B
timeFrame: From randomization to development of local disease recurrence, distance metastasis, or death, whichever came first (up to approximately 72 months)
measure: Overall Survival (OS) in the Contemporaneously Randomized Combination and Monotherapy Participants - Treatment Part B
timeFrame: From randomization to the date of death (up to approximately 72 months)
measure: The Number of Participants With Adverse Events up to 30 Days After Last Dose of Study Therapy - Treatment Part A
timeFrame: From first dose to 30 days post last dose (up to approximately 40 weeks)
measure: The Number of Participants With Adverse Events up to 30 Days After Last Dose of Study Therapy - Treatment Part B
timeFrame: From first dose to 30 days post last dose (up to approximately 40 weeks)
measure: The Number of Participants With Adverse Events up to 100 Days After Last Dose of Study Therapy - Treatment Part A
timeFrame: From first dose to 100 days post last dose (up to approximately 50 weeks)
measure: The Number of Participants With Adverse Events up to 100 Days After Last Dose of Study Therapy - Treatment Part B
timeFrame: From first dose to 100 days post last dose (up to approximately 50 weeks)
measure: 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
timeFrame: From first dose to 30 days post last dose (up to approximately 40 weeks)
measure: 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
timeFrame: From first dose to 30 days post last dose (up to approximately 40 weeks)
measure: 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
timeFrame: From first dose to 100 days post last dose (up to approximately 50 weeks)
measure: 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
timeFrame: From first dose to 100 days post last dose (up to approximately 50 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0019
state: Alabama
city: Springdale
country: United States
facility: Local Institution - 0056
state: Arkansas
city: Los Angeles
country: United States
facility: Local Institution - 0186
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0180
state: California
city: San Francisco
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facility: Local Institution - 0002
state: California
city: Aurora
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state: Colorado
city: Athens
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facility: Local Institution - 0016
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0005
state: Illinois
city: Chicago
country: United States
facility: Local Institution
state: Illinois
city: Saint Louis
country: United States
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state: Missouri
city: Howell
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facility: Local Institution - 0012
state: New Jersey
city: Buffalo
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state: New York
city: New York
country: United States
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state: New York
city: New York
country: United States
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state: New York
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state: Ohio
city: Portland
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state: Oregon
city: Allentown
country: United States
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state: Pennsylvania
city: Greenville
country: United States
facility: Local Institution - 0014
state: South Carolina
city: Chattanooga
country: United States
facility: Local Institution - 0013
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0183
state: Tennessee
city: Fairfax
country: United States
facility: Local Institution - 0057
state: Virginia
city: Capital Federal
country: Argentina
facility: Local Institution - 0178
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Local Institution - 0126
state: Buenos Aires
city: Ciudad Autónoma De Buenos Aires
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state: Buenos Aires
city: Mar Del Plata
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state: Buenos Aires
city: Mar Del Plata
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city: Elizabeth Vale
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state: Sao Paulo
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city: Sao Paulo
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state: British Columbia
city: Saint John
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state: New Brunswick
city: Oshawa
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state: Ontario
city: Toronto
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state: Ontario
city: Montreal
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state: Quebec
city: Rimouski
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state: Quebec
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state: Coquimbo
city: Santiago
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state: Metropolitana
city: Santiago
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state: Valparaiso
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state: Beijing
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state: Beijing
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state: Jiangsu
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state: Jiangxi
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state: Jilin
city: Xi'an
country: China
facility: Local Institution - 0144
state: Shan3xi
city: Yantai
country: China
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state: Shandong
city: Shanghai
country: China
facility: Local Institution - 0137
state: Shanghai
city: Shanghai
country: China
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state: Shanghai
city: Shanghai
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state: Shanghai
city: Shanghai
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state: Shanghai
city: Chengdu
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city: Medellin
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state: Antioquia
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state: Cesar
city: Bogotá
country: Colombia
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city: Floridablanca
country: Colombia
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city: Pereira
country: Colombia
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city: Hradec Kralove
country: Czechia
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city: Olomouc
country: Czechia
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city: Besançon Cedex
country: France
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city: Bordeaux
country: France
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city: La Roche-Sur-Yon Cedex 9
country: France
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city: Lyon Cedex 08
country: France
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country: France
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country: France
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country: France
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country: France
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country: France
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city: Villejuif
country: France
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city: Tubingen
country: Germany
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state: Baden-Württemberg
city: Aachen
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Italy
facility: Local Institution - 0105
city: Cremona
country: Italy
facility: Local Institution - 0172
city: Napoli
country: Italy
facility: Local Institution - 0106
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country: Italy
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city: Roma
country: Italy
facility: Local Institution - 0109
city: Verona
country: Italy
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city: Toyoake Shi
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state: Aichi
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state: Kyoto
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city: Osakasayama-shi
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city: Suita-shi
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state: Osaka
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state: Tokushima
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state: Tokyo
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state: Tokyo
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state: Tokyo
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city: Tijuana
country: Mexico
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state: BAJA California
city: Tuxtla Gutierrez
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state: Chiapas
city: Torreón
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state: Coahuila
city: Ciudad de Mexico
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state: Distrito Federal
city: Tlalpan
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state: Distrito Federal
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state: Jalisco
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state: Sinaloa
city: Merida
country: Mexico
facility: Local Institution - 0196
state: Yucatan
city: Chihuahua
country: Mexico
facility: Local Institution - 0089
city: Monterrey, NL
country: Mexico
facility: Local Institution - 0088
city: San Luis Potosi
country: Mexico
facility: Local Institution - 0169
city: Amsterdam
country: Netherlands
facility: Local Institution - 0066
city: Rotterdam
country: Netherlands
facility: Local Institution - 0067
city: Zwolle
country: Netherlands
facility: Local Institution - 0092
city: Bydgoszcz
country: Poland
facility: Local Institution - 0155
city: Wroclaw
country: Poland
facility: Local Institution - 0038
city: Bucharest
country: Romania
facility: Local Institution - 0243
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0200
city: Cluj
country: Romania
facility: Local Institution - 0247
city: Craiova
country: Romania
facility: Local Institution - 0199
city: Iași
country: Romania
facility: Local Institution - 0202
city: Moscow
country: Russian Federation
facility: Local Institution - 0065
city: Novosibirsk
country: Russian Federation
facility: Local Institution - 0170
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution - 0171
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution - 0021
city: Singapore
country: Singapore
facility: Local Institution - 0018
state: Central Singapore
city: Singapore
country: Singapore
facility: Local Institution - 0017
city: Barcelona
country: Spain
facility: Local Institution - 0204
city: Barcelona
country: Spain
facility: Local Institution - 0206
city: Caceres
country: Spain
facility: Local Institution - 0124
city: Cordoba
country: Spain
facility: Local Institution - 0207
city: Lugo
country: Spain
facility: Local Institution - 0118
city: Madrid
country: Spain
facility: Local Institution - 0114
city: Madrid
country: Spain
facility: Local Institution - 0205
city: Sabadell
country: Spain
facility: Local Institution - 0117
city: Sevilla
country: Spain
facility: Local Institution - 0161
city: Chur
country: Switzerland
facility: Local Institution - 0218
city: Sankt Gallen
country: Switzerland
facility: Local Institution - 0219
city: Zuerich
country: Switzerland
facility: Local Institution - 0225
city: Ankara
country: Turkey
facility: Local Institution - 0209
city: Istanbul
country: Turkey
facility: Local Institution - 0210
city: Istanbul
country: Turkey
facility: Local Institution
city: Southampton
country: United Kingdom
facility: Local Institution - 0075
state: Hampshire
city: Manchester
country: United Kingdom
facility: Local Institution - 0063
city: Northwood
country: United Kingdom
facility: Local Institution - 0071
city: Preston
country: United Kingdom
facility: Local Institution - 0073
city: Swansea
country: United Kingdom
facility: Local Institution - 0072
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Marconi L, Sun M, Beisland C, Klatte T, Ljungberg B, Stewart GD, Dabestani S, Choueiri TK, Bex A. Prevalence, Disease-free, and Overall Survival of Contemporary Patients With Renal Cell Carcinoma Eligible for Adjuvant Checkpoint Inhibitor Trials. Clin Genitourin Cancer. 2021 Apr;19(2):e92-e99. doi: 10.1016/j.clgc.2020.12.005. Epub 2021 Jan 7.