A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Tivozanib hydrochloride; Sorafenib
Intervention description: Tivozanib hydrochloride; Sorafenib
Intervention MeSH terms: Sorafenib; Tivozanib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 350.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center,
      parallel-arm study comparing tivozanib to sorafenib in participants with refractory advanced
      renal cell carcinoma (RCC).

      Participants will be randomized (1:1) to treatment with tivozanib or sorafenib.

      Participants will be stratified by International Metastatic Renal Cell Carcinoma Database
      Consortium (IMDC) risk category (favorable; intermediate; poor) and prior therapy (two prior
      vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI); a prior
      checkpoint inhibitor [programmed cell death -1 protein (PD-1) or PD-1 ligand (PD1-L)
      inhibitor] plus a prior VEGFR TKI; a prior VEGFR TKI plus any other systemic agent).

      All participants will be evaluated for progression free survival, overall survival, objective
      response rate, and the duration of response as well as safety and tolerability.

      Pharmacokinetic (PK) analyses are also included in study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years or older

          -  Participants with metastatic RCC who have failed 2 or 3 prior systemic regimens, one
             of which includes a VEGFR TKI other than sorafenib or tivozanib.

          -  Histologically or cytologically confirmed RCC with a clear cell component
             (participants with pure papillary cell tumor or other non-clear cell histologies,
             including collecting duct, medullary, chromophobe, and unclassified RCC are excluded).

          -  Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST)
             criteria Version 1.1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Life expectancy ≥ 3 months.

        Exclusion Criteria:

          -  Prior treatment with sorafenib or tivozanib.

          -  More than 3 prior regimens for metastatic RCC.

          -  Known central nervous system (CNS) metastases other than stable, treated brain
             metastases. Participants with previously treated brain metastasis will be allowed if
             the brain metastasis has been stable by neuroimaging without steroid treatment for at
             least 3 months following prior treatment (radiotherapy or surgery).

          -  Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or
             coagulation disorders.

          -  Significant serum chemistry abnormalities

          -  Significant cardiovascular disease, including: Active clinically symptomatic left
             ventricular failure, uncontrolled hypertension, myocardial infarction, severe angina,
             or unstable angina within 6 months prior to administration of first dose of study
             drug, history of serious ventricular arrhythmia, cardiac arrhythmias requiring
             anti-arrhythmic medications.

          -  Inadequate recovery from any prior surgical procedure or major surgical procedure
             within 4 weeks prior to administration of first dose of study drug.

          -  Currently active second primary malignancy.