This study will be comparing tivozanib in combination with nivolumab to tivozanib alone in subjects with advanced Renal Cell Carcinoma (RCC) who have had 1 or 2 prior lines of therapy, one of which was an Immune Checkpoint Inhibitor (ICI).
This will be an open-label, randomized, controlled, multicenter, multi-national, parallel-arm study. The study is designed to compare the progression free survival (PFS), overall survival (OS), Objective response rate (ORR), duration of response (DoR), and safety of tivozanib and the combination of tivozanib with nivolumab. Approximately 326 subjects with refractory advanced RCC at approximately 190 sites will be randomized in a 1:1 ratio to treatment with tivozanib plus nivolumab (163 subjects) or tivozanib (163 subjects). Subjects will be randomly assigned to a treatment. Subjects will receive 1.34 mg/day (monotherapy arm) or 0.89mg/day (combination arm) of tivozanib once daily (QD) for 3 weeks followed by 1 week off study drug. One cycle will be defined as 4 weeks: 3 weeks on treatment and 1 week off treatment. Subjects who receive nivolumab will be infused with 1 treatment of nivolumab at specified dose on specified days of each Cycle. Subjects with documented stable disease or an objective response may continue to receive both tivozanib and nivolumab therapy at the same dose and schedule until progression as long as the tolerability is acceptable. Nivolumab will be discontinued in all subjects after 2 years; Tivozanib may be continued after discontinuation of nivolumab until other withdrawal criteria are met. A Safety Follow-up Visit will be performed 30 days (± 7 days) after the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
343
Progression free survival
Comparison of the PFS of tivozanib in combination with nivolumab to tivozanib in subjects with RCC who have progressed following 1 or 2 lines of therapy. PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease \[PD\], radiological) according to Response Evaluation Criteria In Solid Tumors (RECIST), or death due to any reasons whichever comes first.
Time frame: Until progressive disease [PD] (Approximately 30 months)
Overall Survival
Comparsion of the OS of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. OS is defined as the time from the date of randomization to date of death due to any cause.
Time frame: From Screening (Days -28 to -1) until death (Approximately 42 months)
Progression free survival
PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease \[PD\], radiological) according to RECIST, or death due to any reasons whichever comes first. PFS as assessed by investigator.
Time frame: Until progressive disease [PD] (Approximately 30 months)
Objective Response Rate
Comparison of ORR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. ORR is defined as the proportion of subjects with confirmed complete response or confirmed partial response according to RECIST relative to the total population of randomized subjects.
Time frame: From Screening (Days -28 to -1) until PD (Approximately 30 months)
Duration of Response
Comparison of DoR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. DoR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause.
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
Chao Family Comprehensive Cancer Center, UC Irvine
Irvine, California, United States
University of California San Diego
La Jolla, California, United States
Leland Stanford Junior University
Redwood City, California, United States
Kaiser Permanente Riverside Medical Center
Riverside, California, United States
US Oncology - Rocky Mountain Cancer Centers - Midtown
Denver, Colorado, United States
Florida Cancer Specialists & Res Inst
Fort Myers, Florida, United States
Florida Cancer Specialists & Research Institute (FCS) - Tampa Cancer Center Location
St. Petersburg, Florida, United States
The University of Kansas Cancer Center
Westwood, Kansas, United States
University of Kentucky UK Markey Cancer Center
Lexington, Kentucky, United States
...and 129 more locations
Time frame: From Screening (Days -28 to -1) until PD or death (Approximately 30 months)
Number of subjects with serious and non-serious adverse events
Assessment of the safety and tolerability of tivozanib in combination with nivolumab compared to tivozanib.
Time frame: From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)