A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)

AVEO Pharmaceuticals, Inc.350 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

350

Conditions

Carcinoma, Renal Cell

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (191)

University Of UA Cancer Center(UACC)/DH-SJHMC

Phoenix, Arizona, United States

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, United States

Arizona Oncology - Phoenix - Deer Valley Women's Center Loca

Phoenix, Arizona, United States

Arizona Oncology - Scottsdale

Scottsdale, Arizona, United States

City of Hope Comprehensive Breast Cancer Center

Duarte, California, United States

Outcomes

Primary Outcomes

Progression-free Survival (PFS)

The PFS, as assessed by a blinded independent radiological review (IRR), is defined as the time from randomization to first documentation of objective tumor progression (progressive disease) or death due to any reasons whichever comes first. Disease progression per RECIST 1.1 criteria is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Disease progression was assessed every 8 weeks (up to approximately 5 years)

Secondary Outcomes

Overall Survival (OS)

The OS is defined as the time from the date of randomization to date of death due to any cause.

Time frame: Date of randomization to date of death (up to approximately 5 years)

Objective Response Rate (ORR)

The ORR is defined as the percentage of participants who have at least a 30% reduction in the sum of diameters per RECIST (Version 1.1).

Time frame: Every 8 weeks from date of randomization until disease progression (up to approximately 5 years)

Duration of Response (DOR)

The DOR is defined as the time from the first documentation of objective tumor response to the first documentation of tumor progression per RECIST 1.1 or to death due to any cause.

Time frame: Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years)