Clinical Trials/NCT03138512

NCT03138512

Completed

Phase 3

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

Bristol-Myers Squibb198 sites in 6 countries1,641 target enrollmentJuly 7, 2017

ConditionsCarcinoma, Renal Cell

Interventionsnivolumab ipilimumab nivolumab placebo ipilimumab placebo

Drugsnivolumab ipilimumab nivolumab placebo ipilimumab placebo

Overview

Phase: Phase 3
Intervention: nivolumab
Conditions: Carcinoma, Renal Cell
Sponsor: Bristol-Myers Squibb
Enrollment: 1641
Locations: 198
Primary Endpoint: Disease-Free Survival (DFS) by BICR - Treatment Part A and B
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

July 7, 2017

End Date

February 1, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Responsible Party

Sponsor

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

Arms & Interventions

Part A, Arm A: nivolumab + ipilimumab

Intervention: nivolumab

Part A, Arm A: nivolumab + ipilimumab

Intervention: ipilimumab

Part A, Arm B: nivolumab placebo + ipilimumab placebo

Intervention: nivolumab placebo

Part A, Arm B: nivolumab placebo + ipilimumab placebo

Intervention: ipilimumab placebo

Part B, Arm A: nivolumab + ipilimumab

Intervention: nivolumab

Part B, Arm A: nivolumab + ipilimumab

Intervention: ipilimumab

Part B, Arm B: nivolumab placebo + ipilimumab placebo

Intervention: nivolumab placebo

Part B, Arm B: nivolumab placebo + ipilimumab placebo

Intervention: ipilimumab placebo

Part B, Arm C: nivolumab + ipilimumab placebo

Intervention: nivolumab

Part B, Arm C: nivolumab + ipilimumab placebo

Intervention: ipilimumab placebo

Outcomes

Primary Outcomes

Disease-Free Survival (DFS) by BICR - Treatment Part A and B

Time Frame: 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 Outcomes

Overall Survival (OS) - Treatment Part A and B(From randomization to the date of death (up to approximately 72 months))
Overall Survival (OS) Rate (5 Years) - Treatment Part A and B(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))
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))
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))
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))
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))
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))
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))
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))
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))
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))