A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)
- Conditions
- Carcinoma, Renal Cell
- Interventions
- Registration Number
- NCT02627963
- Lead Sponsor
- 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 350
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tivozanib hydrochloride Tivozanib hydrochloride Participants randomized to this arm will receive the study drug, tivozanib hydrochloride. Sorafenib Sorafenib Participants randomized to this arm will receive the comparator drug, sorafenib.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) 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) 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.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Every 8 weeks from date of randomization until disease progression (up to approximately 5 years) 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).
Duration of Response (DOR) Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years) 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.
Overall Survival (OS) Date of randomization to date of death (up to approximately 5 years) The OS is defined as the time from the date of randomization to date of death due to any cause.
Trial Locations
- Locations (185)
Dr. Leon Richard Oncology Centre
🇨🇦Moncton, New Brunswick, Canada
New York Oncology Hematology, PC
🇺🇸Albany, New York, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Fort Worth, Texas, United States
Texas Oncology - Longview Cancer Center
🇺🇸Longview, Texas, United States
P.O. Ss. Annunziata
🇮🇹Chieti, Italy
Institut de cancérologie de Lorraine
🇫🇷Vandoeuvre Les Nancy, Meurthe-et-Moselle, France
H.U.F. Alcorcón
🇪🇸Alcorcón, Madrid, Spain
CHU Dinant Godinne UCL Namur
🇧🇪Yvoir, Namur, Belgium
Universitätsklinikum des Saarlandes
🇩🇪Homburg, Saarland, Germany
Institut de Cancérologie de l'Ouest Site Paul Papin
🇫🇷Angers, Maine-et-Loire, France
H.U.P Hierro-Majadahonda
🇪🇸Majadahonda, Madrid, Spain
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Sunnybrook
🇨🇦Toronto, Ontario, Canada
H.G.U. G. Marañón
🇪🇸Madrid, Spain
Aarhus Universitetshospital
🇩🇰Aarhus C, Central Jutland, Denmark
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Arizona Oncology - Scottsdale
🇺🇸Scottsdale, Arizona, United States
Pécsi Tudományegyetem Klinikai Központ
🇭🇺Pécs, Baranya, Hungary
Zala Megyei Korhaz
🇭🇺Zalaegerszeg, Hungary
Békés Megyei Pándy Kálmán Kórház
🇭🇺Gyula, Békés, Hungary
Országos Onkológiai Intézet
🇭🇺Budapest, Hungary
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Hackensack University Medical Center - John Theurer Cancer
🇺🇸Hackensack, New Jersey, United States
UZ Antwerpen
🇧🇪Edegem, Antwerpen, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
🇧🇪Hasselt, Limburg, Belgium
Kliniken Nordoberpfalz AG, Klinikum Weiden
🇩🇪Weiden, Bayern, Germany
Johann Wolfgang Goethe Universität
🇩🇪Frankfurt am Main, Hessen, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Baden-Württemberg, Germany
London Health Sciences Center
🇨🇦London, Ontario, Canada
Institut Jules Bordet
🇧🇪Bruxelles, Brussels Capital Region, Belgium
Grand Hôpital de Charleroi - Site Notre-Dame
🇧🇪Charleroi, Hainaut, Belgium
CHRU de Tours - Hopital Bretonneau TOURS
🇫🇷Tours CEDEX 1, Indre-et-Loire, France
Institut Paoli-Calmettes
🇫🇷Marseille Cedex 09, France
CHU Ambroise Paré
🇧🇪Mons, Hainaut, Belgium
UZ Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
Evangelisches Krankenhaus Bielefeld
🇩🇪Bielefeld, Nordrhein-Westfalen, Germany
Chu De Poitiers
🇫🇷Poitiers, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Universität Tübingen
🇩🇪Tübingen, Germany
Istituto Oncologico Veneto IOV-IRCCS
🇮🇹Padova, Italy
Azienda Ospedaliera S. Maria di Terni
🇮🇹Terni, Italy
Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina
🇵🇱Otwock, Mazowieckie, Poland
COPERNICUS Podmiot Leczn. Sp z o.o.,Wojew. Centrum Onkologii
🇵🇱Gdansk, Poland
Southampton University Hospitals Nhs Trust
🇬🇧Southampton, Hampshire, United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust
🇬🇧Preston, Lancashire, United Kingdom
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Italy
Uniklinik Köln Klinik und Poliklinik für Urologie
🇩🇪Köln, Nordrhein-Westfalen, Germany
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
Markusovszky Egyetemi Oktatókórház
🇭🇺Szombathely, Hungary
Istituto Clinico Humanitas Rozzano, IRCCS
🇮🇹Rozzano, Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
AOU Policlinico di Modena
🇮🇹Modena, Italy
IRCCS Fondazione "Giovanni Pascale"
🇮🇹Napoli, Italy
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie
🇵🇱Warszawa, Mazowieckie, Poland
NZOZ Vesalius Sp. z o.o.
🇵🇱Krakow, Poland
East Lancashire Hospitals NHS Trust
🇬🇧Blackburn, Lancashire, United Kingdom
Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház
🇭🇺Miskolc, Borsod-Abaúj-Zemplén, Hungary
C.S. Parc Taulí
🇪🇸Sabadell, Barcelona, Spain
Universitätsklinikum Aachen
🇩🇪Aachen, Germany
Casa Sollievo della Sofferenza, IRCCS
🇮🇹San Giovanni Rotondo, Foggia, Italy
Ospedale S.Donato, AUSL 8 di Arezzo
🇮🇹Arezzo, Italy
Szpital Specjalist w Brzozowie Podkarpacki Ośrodek Onkologiczny
🇵🇱Brzozow, Poland
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Egyesített Szent István és Szent László Kórház-Rendelőintéze
🇭🇺Budapest, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo
🇭🇺Szeged, Csongrád, Hungary
Istituto di Candiolo, IRCCS
🇮🇹Candiolo, Torino, Italy
AO Spedali Civili di Brescia, PO Spedali Civili
🇮🇹Brescia, Italy
PU Campus Bio-medico di Roma
🇮🇹Roma, Italy
Usl 7 Siena - Ospedale Alta Valdelsa ASL TOSCANA SUD-EST
🇮🇹Poggibonsi, Siena, Italy
Centro di Riferimento Oncologico IRCCS
🇮🇹Aviano, Italy
ASST-Istituti Ospitalieri di Cremona, AO di Cremona
🇮🇹Cremona, Italy
Ieo, Irccs
🇮🇹Milano, Italy
MAGODENT Sp. z o.o. Szpital Onkologiczno-Kardiologiczny
🇵🇱Warszawa, Mazowieckie, Poland
Cheltenham General Hospital
🇬🇧Cheltenham, Gloucestershire, United Kingdom
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
University Of UA Cancer Center(UACC)/DH-SJHMC
🇺🇸Phoenix, Arizona, United States
Investigative Clinical Research of Indiana
🇺🇸Indianapolis, Indiana, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Urology Cancer Center, PC
🇺🇸Omaha, Nebraska, United States
Arizona Oncology - Phoenix - Deer Valley Women's Center Loca
🇺🇸Phoenix, Arizona, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Midwest Cancer Center
🇺🇸Omaha, Nebraska, United States
Comprehensive Cancer Center Of Nevada
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Center of Nevada
🇺🇸Las Vegas, Nevada, United States
Baylor College of Medicine - Baylor Clinic
🇺🇸Houston, Texas, United States
City of Hope Comprehensive Breast Cancer Center
🇺🇸Duarte, California, United States
Long Beach Memorial Medical Center
🇺🇸Fountain Valley, California, United States
Marin Cancer Care
🇺🇸Greenbrae, California, United States
UCLA
🇺🇸Los Angeles, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
New York Oncology Hematology, P.C.
🇺🇸Clifton Park, New York, United States
Columbia University Medical Center - Herbert Irving Pavilion
🇺🇸New York, New York, United States
Wake Forest University Baptist Medical Center (WFUBMC)
🇺🇸Winston-Salem, North Carolina, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Ohio Cancer Specialists
🇺🇸Mansfield, Ohio, United States
North Coast Cancer Care, Inc
🇺🇸Sandusky, Ohio, United States
St. Luke University Health Network
🇺🇸Easton, Pennsylvania, United States
Wooster Specialty and Surgery Center
🇺🇸Wooster, Ohio, United States
University of Pittsburgh Medical Center (UPMC)
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Oncology - Austin Midtown
🇺🇸Austin, Texas, United States
Texas Oncology-Central Austin Cancer Center
🇺🇸Austin, Texas, United States
Texas Oncology - South Austin Cancer Center
🇺🇸Austin, Texas, United States
Texas Oncology SW Fort Worth Cancer Center
🇺🇸Fort Worth, Texas, United States
Texas Oncology - Fort Worth 12th Ave
🇺🇸Fort Worth, Texas, United States
Nebraska Cancer Specialists (NCS) - Midwest Cancer Center
🇺🇸Fort Worth, Texas, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Comprehensive Cancer Centers of Nevada (CCCN)
🇺🇸Fort Worth, Texas, United States
Texas Oncology-Garland
🇺🇸Garland, Texas, United States
Texas Oncology, P.A.
🇺🇸Plano, Texas, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
🇧🇪Brugge, West-Vlaanderen, Belgium
British Columbia Cancer Agency (BCCA)
🇨🇦Vancouver, British Columbia, Canada
FN Hradec Kralove
🇨🇿Hradec Kralove, Královéhradecký Kraj, Czechia
Masarykuv onkologicky ustav
🇨🇿Brno, Brno-město, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Olomoucký Kraj, Czechia
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czechia
Herlev Hospital
🇩🇰Herlev, Capital, Denmark
Odense Universitetshospital
🇩🇰Odense, South Denmark, Denmark
Hopital Saint-André
🇫🇷Bordeaux Cedex, Gironde, France
Institut de Cancerologie de la Loire
🇫🇷Saint-Priest-en-Jarez, Loire, France
Clinique Victor Hugo
🇫🇷Le Mans, Pays-de-la-Loire, France
centre Oscar Lambret
🇫🇷Lille, Nord-Pas-de-Calais, France
ICO
🇫🇷Saint Herblain CEDEX, France
Univesitaetsklinik Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
SZB Study Center University Hospital Bonn
🇩🇪Bonn, Nordrhein-Westfalen, Germany
Jena University Hospital
🇩🇪Jena, Thüringen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Szent Margit Kórház
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Központ
🇭🇺Debrecen, Hajdú-Bihar, Hungary
Magyar Honvédség Egészségügyi Központ
🇭🇺Budapest, Hungary
Somogy Megyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Hungary
Irccs Irst
🇮🇹Meldola, Forli, Italy
AOU Careggi
🇮🇹Firenze, Italy
Ospedale Vito Fazzi, ASL Lecce
🇮🇹Lecce, Italy
IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca
🇮🇹Genova, Italy
Regina Elena, Istituto Nazionale dei Tumori, IFO, IRCCS
🇮🇹Roma, Italy
Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego
🇵🇱Wroclaw, Poland
H.G.U. de Elche
🇪🇸Elche, Alicante, Spain
Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
H.U.Son Espases
🇪🇸Palma, Baleares, Spain
Institut Catalá d´Oncología (I.C.O.)
🇪🇸L'Hospitalet De Llobregat, Barcelona, Spain
H.del Mar
🇪🇸Barcelona, Spain
H.Sta.Creu i St.Pau
🇪🇸Barcelona, Spain
ICO-H.U.Dr.J.Trueta
🇪🇸Girona, Spain
H.U.Vall d'Hebrón
🇪🇸Barcelona, Spain
H. Clinic de Barcelona
🇪🇸Barcelona, Spain
C.H. de Jaén
🇪🇸Jaén, Spain
H.U. Reina Sofía
🇪🇸Córdoba, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
H.U. Infanta Leonor
🇪🇸Madrid, Spain
H.C. S.Carlos
🇪🇸Madrid, Spain
H.U. F. Jiménez Díaz
🇪🇸Madrid, Spain
H.U.V. Macarena
🇪🇸Sevilla, Spain
H.U. Virgen de la Victoria
🇪🇸Málaga, Spain
F.I. Valenciano de Oncología
🇪🇸Valencia, Spain
H.U.P.La Fe
🇪🇸Valencia, Spain
Beatson West Of Scotland Cancer Centre
🇬🇧Glasgow, Glasgow City, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
H.U. Miguel Servet
🇪🇸Zaragoza, Spain
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
Royal Stroke Center
🇬🇧Stoke-on-Trent, Staffordshire, United Kingdom
St James's University Hospital / Leeds Teaching Hospitals
🇬🇧Leeds, United Kingdom
Mount Vernon Cancer Care
🇬🇧Middlesex, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Nottingham University Hospitals NHS Trust - City Hospital
🇬🇧Nottingham, United Kingdom
Churchill Hospital [Oncology]
🇬🇧Oxford, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Singleton Hospital
🇬🇧Swansea, United Kingdom
Arizona Oncology Associates, PC - HAL
🇺🇸Fort Worth, Texas, United States
Texas Oncology - El Paso Cancer Treatment Center
🇺🇸Fort Worth, Texas, United States
Texas Oncology-El Paso Cancer Treatment Center
🇺🇸Fort Worth, Texas, United States
H.U. 12 de Octubre
🇪🇸Madrid, Spain
H.U. La Paz
🇪🇸Madrid, Spain
H. Madrid Norte Sanchinarro
🇪🇸Madrid, Spain
C.H. de Navarra
🇪🇸Pamplona, Navarra, Spain
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Charing Cross Hospital
🇬🇧London, United Kingdom