Clinical trial NCT02627963: A Study to Compare Tivozanib Hydrochloride to Sorafenib in Participants With Refractory Advanced Renal Cell Carcinoma (RCC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Renal Cell
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-11
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: Date of randomization to date of death (up to approximately 5 years)
measure: Objective Response Rate (ORR)
timeFrame: Every 8 weeks from date of randomization until disease progression (up to approximately 5 years)
measure: Duration of Response (DOR)
timeFrame: Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: University Of UA Cancer Center(UACC)/DH-SJHMC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology - Phoenix - Deer Valley Women's Center Loca
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Oncology - Scottsdale
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Breast Cancer Center
state: California
city: Fountain Valley
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Care
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Investigative Clinical Research of Indiana
state: Indiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Omaha
country: United States
facility: Midwest Cancer Center
state: Nebraska
city: Omaha
country: United States
facility: Urology Cancer Center, PC
state: Nebraska
city: Henderson
country: United States
facility: Comprehensive Cancer Center Of Nevada
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center Of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center of Nevada
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center - John Theurer Cancer
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Albany
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Clifton Park
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Pavilion
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center (WFUBMC)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Mansfield
country: United States
facility: Ohio Cancer Specialists
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care, Inc
state: Ohio
city: Wooster
country: United States
facility: Wooster Specialty and Surgery Center
state: Ohio
city: Easton
country: United States
facility: St. Luke University Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Austin
country: United States
facility: Texas Oncology-Central Austin Cancer Center
state: Texas
city: Austin
country: United States
facility: Texas Oncology - South Austin Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth 12th Ave
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology SW Fort Worth Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Texas
city: Fort Worth
country: United States
facility: Comprehensive Cancer Centers of Nevada (CCCN)
state: Texas
city: Fort Worth
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Texas
city: Fort Worth
country: United States
facility: Nebraska Cancer Specialists (NCS) - Midwest Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - El Paso Cancer Treatment Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-El Paso Cancer Treatment Center
state: Texas
city: Garland
country: United States
facility: Texas Oncology-Garland
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Baylor Clinic
state: Texas
city: Longview
country: United States
facility: Texas Oncology - Longview Cancer Center
state: Texas
city: Plano
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Edegem
country: Belgium
facility: UZ Antwerpen
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
state: Brussels Capital Region
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi - Site Notre-Dame
state: Hainaut
city: Mons
country: Belgium
facility: CHU Ambroise Paré
state: Hainaut
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
state: Limburg
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne UCL Namur
state: Namur
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
state: West-Vlaanderen
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency (BCCA)
state: British Columbia
city: Moncton
country: Canada
facility: Dr. Leon Richard Oncology Centre
state: New Brunswick
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook
state: Ontario
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
state: Brno-město
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove
state: Královéhradecký Kraj
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
state: Olomoucký Kraj
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Herlev
country: Denmark
facility: Herlev Hospital
state: Capital
city: Aarhus C
country: Denmark
facility: Aarhus Universitetshospital
state: Central Jutland
city: Odense
country: Denmark
facility: Odense Universitetshospital
state: South Denmark
city: Bordeaux Cedex
country: France
facility: Hopital Saint-André
state: Gironde
city: Tours CEDEX 1
country: France
facility: CHRU de Tours - Hopital Bretonneau TOURS
state: Indre-et-Loire
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancerologie de la Loire
state: Loire
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest Site Paul Papin
state: Maine-et-Loire
city: Vandoeuvre Les Nancy
country: France
facility: Institut de cancérologie de Lorraine
state: Meurthe-et-Moselle
city: Lille
country: France
facility: centre Oscar Lambret
state: Nord-Pas-de-Calais
city: Le Mans
country: France
facility: Clinique Victor Hugo
state: Pays-de-la-Loire
city: Marseille Cedex 09
country: France
facility: Institut Paoli-Calmettes
city: Poitiers
country: France
facility: Chu De Poitiers
city: Saint Herblain CEDEX
country: France
facility: ICO
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: Univesitaetsklinik Heidelberg
state: Baden-Württemberg
city: Weiden
country: Germany
facility: Kliniken Nordoberpfalz AG, Klinikum Weiden
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Johann Wolfgang Goethe Universität
state: Hessen
city: Bielefeld
country: Germany
facility: Evangelisches Krankenhaus Bielefeld
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: SZB Study Center University Hospital Bonn
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Uniklinik Köln Klinik und Poliklinik für Urologie
state: Nordrhein-Westfalen
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
state: Saarland
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Jena
country: Germany
facility: Jena University Hospital
state: Thüringen
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Tübingen
country: Germany
facility: Universität Tübingen
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ
state: Baranya
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház
state: Borsod-Abaúj-Zemplén
city: Gyula
country: Hungary
facility: Békés Megyei Pándy Kálmán Kórház
state: Békés
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo
state: Csongrád
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
state: Hajdú-Bihar
city: Budapest
country: Hungary
facility: Szent Margit Kórház
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet
city: Budapest
country: Hungary
facility: Egyesített Szent István és Szent László Kórház-Rendelőintéze
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház
city: Szombathely
country: Hungary
facility: Markusovszky Egyetemi Oktatókórház
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Korhaz
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo della Sofferenza, IRCCS
state: Foggia
city: Meldola
country: Italy
facility: Irccs Irst
state: Forli
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas Rozzano, IRCCS
state: Milano
city: Poggibonsi
country: Italy
facility: Usl 7 Siena - Ospedale Alta Valdelsa ASL TOSCANA SUD-EST
state: Siena
city: Candiolo
country: Italy
facility: Istituto di Candiolo, IRCCS
state: Torino
city: Arezzo
country: Italy
facility: Ospedale S.Donato, AUSL 8 di Arezzo
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico IRCCS
city: Brescia
country: Italy
facility: AO Spedali Civili di Brescia, PO Spedali Civili
city: Chieti
country: Italy
facility: P.O. Ss. Annunziata
city: Cremona
country: Italy
facility: ASST-Istituti Ospitalieri di Cremona, AO di Cremona
city: Firenze
country: Italy
facility: AOU Careggi
city: Genova
country: Italy
facility: IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi, ASL Lecce
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Ieo, Irccs
city: Modena
country: Italy
facility: AOU Policlinico di Modena
city: Napoli
country: Italy
facility: IRCCS Fondazione "Giovanni Pascale"
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IOV-IRCCS
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: PU Campus Bio-medico di Roma
city: Roma
country: Italy
facility: Regina Elena, Istituto Nazionale dei Tumori, IFO, IRCCS
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria di Terni
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie
state: Mazowieckie
city: Warszawa
country: Poland
facility: MAGODENT Sp. z o.o. Szpital Onkologiczno-Kardiologiczny
state: Mazowieckie
city: Brzozow
country: Poland
facility: Szpital Specjalist w Brzozowie Podkarpacki Ośrodek Onkologiczny
city: Gdansk
country: Poland
facility: COPERNICUS Podmiot Leczn. Sp z o.o.,Wojew. Centrum Onkologii
city: Krakow
country: Poland
facility: NZOZ Vesalius Sp. z o.o.
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego
city: Elche
country: Spain
facility: H.G.U. de Elche
state: Alicante
city: Palma
country: Spain
facility: H.U.Son Espases
state: Baleares
city: Badalona
country: Spain
facility: Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: L'Hospitalet De Llobregat
country: Spain
facility: Institut Catalá d´Oncología (I.C.O.)
state: Barcelona
city: Sabadell
country: Spain
facility: C.S. Parc Taulí
state: Barcelona
city: Alcorcón
country: Spain
facility: H.U.F. Alcorcón
state: Madrid
city: Majadahonda
country: Spain
facility: H.U.P Hierro-Majadahonda
state: Madrid
city: Pamplona
country: Spain
facility: C.H. de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: H.del Mar
city: Barcelona
country: Spain
facility: H.Sta.Creu i St.Pau
city: Barcelona
country: Spain
facility: H.U.Vall d'Hebrón
city: Barcelona
country: Spain
facility: H. Clinic de Barcelona
city: Córdoba
country: Spain
facility: H.U. Reina Sofía
city: Girona
country: Spain
facility: ICO-H.U.Dr.J.Trueta
city: Jaén
country: Spain
facility: C.H. de Jaén
city: Madrid
country: Spain
facility: H.G.U. G. Marañón
city: Madrid
country: Spain
facility: H.U. Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: H.C. S.Carlos
city: Madrid
country: Spain
facility: H.U. F. Jiménez Díaz
city: Madrid
country: Spain
facility: H.U. 12 de Octubre
city: Madrid
country: Spain
facility: H.U. La Paz
city: Madrid
country: Spain
facility: H. Madrid Norte Sanchinarro
city: Málaga
country: Spain
facility: H.U. Virgen de la Victoria
city: Sevilla
country: Spain
facility: H.U.V. Macarena
city: Valencia
country: Spain
facility: F.I. Valenciano de Oncología
city: Valencia
country: Spain
facility: H.U.P.La Fe
city: Zaragoza
country: Spain
facility: H.U. Miguel Servet
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: Cambridgeshire
city: Glasgow
country: United Kingdom
facility: Beatson West Of Scotland Cancer Centre
state: Glasgow City
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: Gloucestershire
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals Nhs Trust
state: Hampshire
city: Blackburn
country: United Kingdom
facility: East Lancashire Hospitals NHS Trust
state: Lancashire
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust
state: Lancashire
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stroke Center
state: Staffordshire
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Leeds
country: United Kingdom
facility: St James's University Hospital / Leeds Teaching Hospitals
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Middlesex
country: United Kingdom
facility: Mount Vernon Cancer Care
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital [Oncology]
city: Swansea
country: United Kingdom
facility: Singleton Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
References:
citation: Szarek M, Needle MN, Rini BI, Pal SK, McDermott DF, Atkins MB, Hutson TE, Escudier BJ. Q-TWiST Analysis of Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma in the TIVO-3 Study. Clin Genitourin Cancer. 2021 Oct;19(5):468.e1-468.e5. doi: 10.1016/j.clgc.2021.03.018. Epub 2021 Apr 3.
citation: Rini BI, Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, Verzoni E, Needle MN, McDermott DF. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020 Jan;21(1):95-104. doi: 10.1016/S1470-2045(19)30735-1. Epub 2019 Dec 3.