NCT02627963|CompletedPhase 3Results

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

A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced Renal Cell Carcinoma

AVEO Pharmaceuticals, Inc.ClinicalTrials.gov

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1 other identifier

AV-951-15-303

Study Type

interventional

Target

350

Locations

12 countries

Sites

191

Timeline

RegisteredDec 2015

StartedMay 2016

CompletionJun 2021

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

350

participants targeted

Target at P50-P75 for phase_3

Timeline

Completed

Started May 2016

Longer than P75 for phase_3

Geographic Reach

12 countries

191 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.1 years study duration

First Submitted

Initial submission to the registry

December 9, 2015

Completed

2 days until next milestone

First Posted

Study publicly available on registry

December 11, 2015

Completed

6 months until next milestone

Study Start

First participant enrolled

May 24, 2016

Completed

2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 4, 2018

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

February 20, 2020

Completed

1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 21, 2021

Completed

Last Updated

July 18, 2023

Status Verified

June 1, 2023

Enrollment Period

2.4 years

First QC Date

December 9, 2015

Results QC Date

January 16, 2020

Last Update Submit

June 27, 2023

Conditions

Carcinoma, Renal Cell

Outcome Measures

Primary Outcomes (1)

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.
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 (3)

Overall Survival (OS)
Date of randomization to date of death (up to approximately 5 years)
Objective Response Rate (ORR)
Every 8 weeks from date of randomization until disease progression (up to approximately 5 years)
Duration of Response (DOR)
Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years)

Study Arms (2)

Tivozanib hydrochloride

EXPERIMENTAL

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

Drug: Tivozanib hydrochloride

Sorafenib

ACTIVE COMPARATOR

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

Drug: Sorafenib

Interventions

Tivozanib hydrochlorideDRUG

Tivozanib hydrochloride

SorafenibDRUG

Sorafenib

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

AVEO Pharmaceuticals, Inc.lead

Study Sites (191)

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

Phoenix, Arizona, 85004, United States

Location

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, 85016, United States

Location

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

Phoenix, Arizona, 85027, United States

Location

Arizona Oncology - Scottsdale

Scottsdale, Arizona, 85258, United States

Location

City of Hope Comprehensive Breast Cancer Center

Duarte, California, 91010, United States

Location

Long Beach Memorial Medical Center

Fountain Valley, California, 92708, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Investigative Clinical Research of Indiana

Indianapolis, Indiana, 46260, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Midwest Cancer Center

Omaha, Nebraska, 68130, United States

Location

Urology Cancer Center, PC

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Center Of Nevada

Henderson, Nevada, 89052, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89074, United States

Location

Comprehensive Cancer Center Of Nevada

Las Vegas, Nevada, 89128, United States

Location

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, 89148, United States

Location

Hackensack University Medical Center - John Theurer Cancer

Hackensack, New Jersey, 07601, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12206, United States

Location

New York Oncology Hematology, PC

Albany, New York, 12208, United States

Location

New York Oncology Hematology, P.C.

Clifton Park, New York, 12065, United States

Location

New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Wake Forest University Baptist Medical Center (WFUBMC)

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio Cancer Specialists

Mansfield, Ohio, 44906, United States

Location

North Coast Cancer Care, Inc

Sandusky, Ohio, 44870, United States

Location

Wooster Specialty and Surgery Center

Wooster, Ohio, 44691, United States

Location

St. Luke University Health Network

Easton, Pennsylvania, 18045, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15232, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology-Central Austin Cancer Center

Austin, Texas, 78731, United States

Location

Texas Oncology - South Austin Cancer Center

Austin, Texas, 78745, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology - Fort Worth 12th Ave

Fort Worth, Texas, 76104, United States

Location

Texas Oncology SW Fort Worth Cancer Center

Fort Worth, Texas, 76132, United States

Location

Arizona Oncology Associates, PC - HAL