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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04987203
Other study ID # AV-951-20-304
Secondary ID
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date September 9, 2021
Est. completion date August 1, 2025

Study information

Verified date April 2024
Source AVEO Pharmaceuticals, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study will be comparing tivozanib in combination with nivolumab to tivozanib alone in subjects with advanced Renal Cell Carcinoma (RCC) who have had 1 or 2 prior lines of therapy, one of which was an Immune Checkpoint Inhibitor (ICI).


Description:

This will be an open-label, randomized, controlled, multicenter, multi-national, parallel-arm study. The study is designed to compare the progression free survival (PFS), overall survival (OS), Objective response rate (ORR), duration of response (DoR), and safety of tivozanib and the combination of tivozanib with nivolumab. Approximately 326 subjects with refractory advanced RCC at approximately 190 sites will be randomized in a 1:1 ratio to treatment with tivozanib plus nivolumab (163 subjects) or tivozanib (163 subjects). Subjects will be randomly assigned to a treatment. Subjects will receive 1.34 mg/day (monotherapy arm) or 0.89mg/day (combination arm) of tivozanib once daily (QD) for 3 weeks followed by 1 week off study drug. One cycle will be defined as 4 weeks: 3 weeks on treatment and 1 week off treatment. Subjects who receive nivolumab will be infused with 1 treatment of nivolumab at specified dose on specified days of each Cycle. Subjects with documented stable disease or an objective response may continue to receive both tivozanib and nivolumab therapy at the same dose and schedule until progression as long as the tolerability is acceptable. Nivolumab will be discontinued in all subjects after 2 years; Tivozanib may be continued after discontinuation of nivolumab until other withdrawal criteria are met. A Safety Follow-up Visit will be performed 30 days (± 7 days) after the last dose of study drug.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 343
Est. completion date August 1, 2025
Est. primary completion date August 1, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 130 Years
Eligibility Inclusion Criteria: - Radiographic disease progression during or following at least 6 weeks of treatment with ICI for locally advanced or metastatic RCC with a clear cell component either in first- or second-line treatment. - Subjects must have recovered from the adverse events of prior therapy to grade = 1 or baseline. - Histologically or cytologically confirmed RCC with a clear cell component. - Measurable disease per RECIST criteria Version 1.1. - Eastern Cooperative Oncology Group performance status of 0 or 1. - All participants must follow protocol defined contraceptive measures. Exclusion Criteria: - Subjects who received: a. A single agent tyrosine kinase inhibitor (TKI) in the first line setting followed by a single agent immune checkpoint inhibitor (ICI) in the second line setting; b. More than 2 prior lines of therapy in the advanced or metastatic setting. - History of life-threatening toxicity related to prior immune therapy. - Active autoimmune disease as well as those that required discontinuation of prior immuno-oncological (IO) therapy due to immune mediated AEs. - Uncontrolled hypertension. - More than 1 prior line of therapy with a checkpoint inhibitor in the metastatic setting. - Subjects on immune suppressive therapy for organ transplant or subjects with a history of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV) [Patients with HIV who have CD4+ T-cell counts >350 cells/µL, without a history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections, and are on established antiretroviral therapy which does not include a cytochrome P450 (CYP)3A4 inducer, for at least 4 weeks and have an HIV viral load less than 400 copies/mL, are eligible]. - History of clinically significant interstitial lung disease or current non-infectious pneumonitis.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Tivozanib
Tivozanib will be administered orally.
Nivolumab
Nivolumab will be administered via intravenous infusion.

Locations

Country Name City State
Argentina Centro Oncológico Korben Buenos Aires Ciudad Autónoma De Buenos Aire
Argentina Centro Oncologico de Rosario Rosario Santa Fe
Argentina Centro para la Atención Integral del paciente Oncológico San Miguel de Tucumán Tucumán
Argentina Clínica Viedma Viedma Río Negro
Australia Mater Misericordiae Limited Brisbane Queensland
Australia Sunshine Hospital Geelong Victoria
Australia Liverpool Hospital Cancer Therapy Centre Liverpool New South Wales
Australia Princess Alexandra Hospital Woolloongabba Queensland
Belgium Institut Jules Bordet - Oncologie Médicale Anderlecht Brussels Capital Region
Belgium CHU Brugmann - Victor Horta Bruxelles
Belgium UZ Gent - Medische Oncologie Gent Oost-Vlaanderen
Belgium Jessa Ziekenhuis - Campus Virga Jesse - Medische Oncologie Hasselt Limburg
Belgium AZ Groeninge - Campus Kennedylaan Kortrijk
Belgium ZNA Jan Palfijn Merksen Antwerpen
Brazil Universidade Estadual de Campi Campinas São Paulo
Brazil Clinica de Neoplasias Litoral Itajai Santa Catarina
Brazil Centro Gaucho Integrado de Onc Porto Alegre Rio Grande Do Sul
Brazil Hospital Nossa Senhora da Conc Porto Alegre
Brazil Pontificia Universidade Porto Alegre
Brazil Instituto Brasileiro de Controle do Cancer - ibcc São Paulo
Canada Tom Baker Cancer Centre Calgary Alberta
Canada Sunnybrook Research Institute, sunnybrook Health Sciences Ct Toronto Ontario
Canada University Health Network - Princess Margaret Cancer Centre Toronto Ontario
Canada BC Cancer - Vancouver Centre Vancouver British Columbia
Chile Centro de Estudios Clinicos In Santiago Región Metropolitana De Santia
Chile Centro de Estudios Clínicos SAGA SpA Santiago Región Metropolitana De Santia
Chile Meditek Ltda. Santiago de Chile Región Metropolitana De Santiago
Chile ACEREY Centro de Investigación Clínica Oncológica Viña del mar Valparaíso
Czechia FN Hradec Kralove Hradec Kralove
Czechia FN Kralovske Vinohrady Praha 10
Czechia Fakultni Thomayerova nemocnice Praha 4
France Hopital Saint-Andre - Service d'Oncologie Medicale Bordeaux Gironde
France CHU Michallon - Hopital Nord - Cancérologie Et Hématologie Grenoble Isère
France CHD Vendee La Roche sur Yon - Gastro-Entérologie La Roche-sur-Yon
France Clinique Victor Hugo - Hematologie Le Mans Sarthe
France Hôpital privé Le Bois Lille Nord
France Centre Leon Berard - departement d'oncologie medicale Lyon Rhône
France Institut Paoli Calmettes - Hôpital de jour Marseille Bouches-du-Rhône
France Centre de Lutte Contre le Cancer (CLCC) Nice
France Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud Pierre-Bénite Rhône-Alpes
France Centre Hospitalier de Poitiers Poitiers Poitou-Charentes
France ICO - Site Rene Gauducheau - Oncologie Medicale St Herblain
France Institut de cancérologie de Strasbourg Europe - ICANS Strasbourg Alsace
France Hopital Foch Suresnes Hauts-de-Seine
France Hopital Trousseau - medical oncology Tours
France Institut de Cancérologie de Lorraine Vandœuvre-lès-Nancy
France Centre de Lutte Contre le Cancer (CLCC) - Gustave Roussy (Institut de Cancerologie Gustave-Roussy) Villejuif Île-de-France
Germany Medizinische Hochschule Hannover Hannover Niedersachsen
Germany Universitätsklinikum Heidelberg Heidelberg Baden-Württemberg
Italy Ospedale S.Donato, AUSL 8 di Arezzo Arezzo
Italy Azienda Mater Domini Catanzaro
Italy P.O. Ss. Annunziata Chieti Scalo Chieti
Italy PO di Cremona, ASST di Cremona - Oncologia medica Cremona
Italy AOUC Azienda Ospedaliero-Universitaria Careggi Firenze
Italy IRST Meldola (Fc) Forli
Italy European Institute of Oncology Milano
Italy IRCCS Fondazione "Giovanni Pas Napoli
Italy IRCCS Policlinico San Matteo Pavia
Italy AO S.Camillo-Forlanini Roma
Italy Fondazione Policlinico Universitario Agostino Gemelli Roma
Italy Azienda Ospedaliera Santa Maria di Terni Terni
Mexico Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Tlalpan
Poland Wojewodzki Szpital Specjalistyczny Biala Podlaska
Poland Szpital Specjalist. w Brzozowie,Podkarpacki Osrodek Onkologi Brzozow Podkarpackie
Poland COPERNICUS Podmiot Leczn. Sp z o.o.,Wojew. Centrum Onkologii Gdansk Pomorskie
Poland Szpital Specjalistyczny im. L. Rydygiera w Krakowie Kraków Malopolskie
Poland Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina Otwock Mazowieckie
Poland Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu Poznan Wielkopolskie
Poland Nzoz Mrukmed Lekarz Beata Madej-Mruk I Partner Sp. P. Rzeszow Podkarpackie
Poland Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych Warszawa
Poland Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa
Portugal H. Prof. Doutor Fernando Fonseca Amadora Lisboa
Portugal Hospital Particular do Algarve - Gambelas-Faro Faro
Portugal H. de Santa Maria. Centro Hospitalar Lisboa Norte - Oncologia Lisboa
Portugal H. Santo Antonio. Centro Hospitalar do Porto Porto
Portugal Instituto Português Oncologia Francisco Gentil do Porto Porto
Spain Hospital de La Santa Creu i Sant Pau Barcelona
Spain Hospital Del Mar Barcelona
Spain Hospital Universitario Vall d' Barcelona
Spain Institut Catalá d´Oncología (I.C.O.) Barcelona
Spain H.G.U. de Elche Elche Alicante
Spain ICO-Hospital Universitari de G Girona
Spain Hospital Clínico San Carlos Madrid
Spain Hospital U. 12 Octubre Madrid
Spain Hospital Universitario La Paz Madrid
Spain Hospital Universitario Ramón y Cajal Madrid
Spain C.H.U. de Orense Orense
Spain Hospital Universitario Son Espases Palma de Mallorca Baleares
Spain Hospital Universitari Parc Tau Sabadell Barcelona
Spain Hospital Universitario Virgen Sevilla
Spain Fundación Instituto Valenciano Valencia
Spain Hospital Universitario Y Politécnico La Fe Valencia Valenciana, Comunidad
United Kingdom Addenbrooke's Hospital - Oncology Cambridge Cambridgeshire
United Kingdom Royal Derby Hospital Derby
United Kingdom Leeds Teaching Hospitals NHS Trust Leeds
United Kingdom Imperial College Healthcare NHS Trust - Hammersmith Hospital London London, City Of
United Kingdom The Christie NHS Foundation Trust - Medical Oncology Manchester
United Kingdom Mount Vernon Cancer Centre Northwood England
United Kingdom Royal Blackburn Hospital - Oncology Preston Lancashire
United Kingdom Royal Marsden - Sutton Sutton Surrey
United Kingdom Royal Marsden Hospital Sutton Surrey
United Kingdom New Cross Hospital Wolverhampton
United States University of New Mexico - Comprehensive Cancer Center Albuquerque New Mexico
United States Lehigh Valley Physician Group Allentown Pennsylvania
United States Texas Oncology - Central Austin Cancer Center Austin Texas
United States John Hopkins Medicine - Hematology/oncology Baltimore Maryland
United States University of Maryland Medical Center-Greenebaum Cancer Ctr Baltimore Maryland
United States St. Vincent Frontier Cancer Center Billings Montana
United States Dana-Farber Cancer Institute - Medicine Boston Massachusetts
United States Roswell - Roswell Park Cancer Institute - Medical Oncology Buffalo New York
United States Chattanooga Oncology and Hematology Associates Chattanooga Tennessee
United States Cleveland Clinic Cleveland Ohio
United States Maryland Oncology Hematology Clinton Maryland
United States UH Cleveland Medical Center Columbia South Carolina
United States Texas Oncology - Baylor Charles A. Sammons Cancer Center Dallas Texas
United States US Oncology - Rocky Mountain Cancer Centers - Midtown Denver Colorado
United States Henry Ford Hospital Detroit Michigan
United States City of Hope Comprehensive Cancer Center Duarte California
United States Florida Cancer Specialists & Res Inst Fort Myers Florida
United States Memorial Sloan Kettering Cancer Center - Westchester Harrison New York
United States Chao Family Comprehensive Cancer Center, UC Irvine Irvine California
United States University of California San Diego La Jolla California
United States University of Kentucky UK Markey Cancer Center Lexington Kentucky
United States Tennessee Oncology, PLLC Nashville Tennessee
United States Vanderbilt-Ingram Cancer Center Nashville Tennessee
United States Tulane Cancer Center Clinic - Oncology New Orleans Louisiana
United States Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital New York New York
United States Oncology Hematology West PC dba Nebraska Cancer Specialists Omaha Nebraska
United States Allegheny General Hospital (AGH) Pittsburgh Pennsylvania
United States Leland Stanford Junior University Redwood City California
United States Kaiser Permanente Riverside Medical Center Riverside California
United States Florida Cancer Specialists & Research Institute (FCS) - Tampa Cancer Center Location Saint Petersburg Florida
United States US Oncology Texas Oncology (CCC of South Texas) - San Antonio Medical Center San Antonio Texas
United States University Of Washington - Medical Center Seattle Washington
United States Northwest Medical Specialties PLLC Tacoma Washington
United States Memorial Sloan Kettering Cancer Center - Nassau Uniondale New York
United States The University of Kansas Cancer Center Westwood Kansas

Sponsors (3)

Lead Sponsor Collaborator
AVEO Pharmaceuticals, Inc. Bristol-Myers Squibb, Parexel

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Germany,  Italy,  Mexico,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression free survival Comparison of the PFS of tivozanib in combination with nivolumab to tivozanib in subjects with RCC who have progressed following 1 or 2 lines of therapy. PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease [PD], radiological) according to Response Evaluation Criteria In Solid Tumors (RECIST), or death due to any reasons whichever comes first. Until progressive disease [PD] (Approximately 30 months)
Secondary Overall Survival Comparsion of the OS of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. OS is defined as the time from the date of randomization to date of death due to any cause. From Screening (Days -28 to -1) until death (Approximately 42 months)
Secondary Progression free survival PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease [PD], radiological) according to RECIST, or death due to any reasons whichever comes first. PFS as assessed by investigator. Until progressive disease [PD] (Approximately 30 months)
Secondary Objective Response Rate Comparison of ORR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. ORR is defined as the proportion of subjects with confirmed complete response or confirmed partial response according to RECIST relative to the total population of randomized subjects. From Screening (Days -28 to -1) until PD (Approximately 30 months)
Secondary Duration of Response Comparison of DoR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. DoR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause. From Screening (Days -28 to -1) until PD or death (Approximately 30 months)
Secondary Number of subjects with serious and non-serious adverse events Assessment of the safety and tolerability of tivozanib in combination with nivolumab compared to tivozanib. From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)
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