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A Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced RCC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02627963
Recruitment Status : Completed
First Posted : December 11, 2015
Results First Posted : February 20, 2020
Last Update Posted : January 26, 2022
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.

Brief Summary:

This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center, parallel-arm study comparing tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC).

Subjects will be randomized (1:1) to treatment with tivozanib or sorafenib.

Subjects 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 subjects 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) analysis are also included in study.

Condition or disease Intervention/treatment Phase
Carcinoma, Renal Cell Drug: tivozanib hydrochloride Drug: Sorafenib Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced Renal Cell Carcinoma
Actual Study Start Date : April 2016
Actual Primary Completion Date : December 2018
Actual Study Completion Date : June 2021

Arm Intervention/treatment
Experimental: Tivozanib hydrochloride
Patients randomized to this arm will receive the study drug, tivozanib hydrochloride.
Drug: tivozanib hydrochloride
tivozanib hydrochloride

Active Comparator: Sorafenib
Patients randomized to this arm will receive the comparator drug, sorafenib.
Drug: Sorafenib

Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ 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. ]
    Progression-Free Survival (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.

Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Date of randomization to date of death ]
    Overall survival (OS) is defined as the time from the date of randomization to date of death due to any cause.

  2. Objective Response Rate (ORR) [ Time Frame: Every 8 weeks from date of randomization until disease progression ]
    Objective response rate (ORR) is defined as the percentage of subjects who have at least a 30% reduction in the sum of diameters per RECIST (Version 1.1).

  3. Duration of Response (DOR) [ Time Frame: Assessed every 8 weeks from date of randomization until date of progression ]
    Duration of response (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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 18 years or older
  • Subjects 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 (subjects 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. Subjects 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02627963

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Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by AVEO Pharmaceuticals, Inc.:
Study Protocol  [PDF] October 1, 2018
Statistical Analysis Plan  [PDF] October 1, 2018

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: AVEO Pharmaceuticals, Inc. Identifier: NCT02627963    
Other Study ID Numbers: AV-951-15-303
First Posted: December 11, 2015    Key Record Dates
Results First Posted: February 20, 2020
Last Update Posted: January 26, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action