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

Carcinoma, Renal Cell Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02627963
• Other study ID #: AV-951-15-303
• Status: Completed
• Phase: Phase 3
• Start date: May 24, 2016
• Est. completion date: June 21, 2021

Study information

• Verified date: June 2023
• Source: AVEO Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: June 21, 2021
• Est. primary completion date: October 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• Tivozanib hydrochloride
Tivozanib hydrochloride
• Sorafenib
Sorafenib

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AVEO Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	The OS is defined as the time from the date of randomization to date of death due to any cause.	Date of randomization to date of death (up to approximately 5 years)
Secondary	Objective Response Rate (ORR)	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).	Every 8 weeks from date of randomization until disease progression (up to approximately 5 years)
Secondary	Duration of Response (DOR)	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.	Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years)