Phase 3
N=350
A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)
Carcinoma, Renal Cell
Bottom Line
View on ClinicalTrials.gov: NCT02627963 ↗Enrolled (actual)
350
Serious AEs
43.2%
Results posted
Feb 2020
Primary outcome: Primary: Progression-free Survival (PFS) — 5.59; 3.88 Months — p=0.0165
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tivozanib hydrochloride (Drug); Sorafenib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AVEO Pharmaceuticals, Inc.
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) |
5.59; 3.88 | 0.0165 sig |
| SECONDARY Overall Survival (OS) |
16.39; 19.15 | 0.8174 |
| SECONDARY Objective Response Rate (ORR) |
31; 14 | — |
| SECONDARY Duration of Response (DOR) |
NA; 5.65 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02627963). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.