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

AVEO Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Carcinoma, Renal Cell

Treatments: Drug: Sorafenib; Drug: Tivozanib hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT02627963

AV-951-15-303

Details and patient eligibility

About

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.

Enrollment: 350 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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350 participants in 2 patient groups

Tivozanib hydrochloride

Experimental group

Description:

Participants randomized to this arm will receive the study drug, tivozanib hydrochloride.

Treatment:

Drug: Tivozanib hydrochloride

Sorafenib

Active Comparator group

Description:

Participants randomized to this arm will receive the comparator drug, sorafenib.

Treatment:

Drug: Sorafenib