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A Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced RCC

Sponsor
AVEO Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02627963
Collaborator
(none)
350
Enrollment
191
Locations
2
Arms
62
Actual Duration (Months)
1.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center, parallel-arm study comparing tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC).

Subjects will be randomized (1:1) to treatment with tivozanib or sorafenib.

Subjects 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 subjects 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) analysis are also included in study.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
350 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Apr 1, 2016
Actual Primary Completion Date :
Dec 1, 2018
Actual Study Completion Date :
Jun 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tivozanib hydrochloride

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

Drug: tivozanib hydrochloride
tivozanib hydrochloride
Active Comparator: Sorafenib

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

Drug: Sorafenib
Sorafenib

Outcome Measures

Primary Outcome Measures

  1. 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.]

    Progression-Free Survival (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

  1. Overall Survival (OS) [Date of randomization to date of death]

    Overall survival (OS) is defined as the time from the date of randomization to date of death due to any cause.

  2. Objective Response Rate (ORR) [Every 8 weeks from date of randomization until disease progression]

    Objective response rate (ORR) is defined as the percentage of subjects who have at least a 30% reduction in the sum of diameters per RECIST (Version 1.1).

  3. Duration of Response (DOR) [Assessed every 8 weeks from date of randomization until date of progression]

    Duration of response (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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • 18 years or older

  • Subjects 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 (subjects 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. Subjects 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 University Of UA Cancer Center(UACC)/DH-SJHMC Phoenix Arizona United States 85004
2 Arizona Oncology Associates, PC - HAL Phoenix Arizona United States 85016
3 Arizona Oncology - Phoenix - Deer Valley Women's Center Loca Phoenix Arizona United States 85027
4 Arizona Oncology - Scottsdale Scottsdale Arizona United States 85258
5 City of Hope Comprehensive Breast Cancer Center Duarte California United States 91010
6 Long Beach Memorial Medical Center Fountain Valley California United States 92708
7 Marin Cancer Care Greenbrae California United States 94904
8 UCLA Los Angeles California United States 90095
9 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
10 Mount Sinai Comprehensive Cancer Center Miami Beach Florida United States 33140
11 University of Miami Sylvester Comprehensive Cancer Center Miami Florida United States 33136
12 Loyola University Medical Center Maywood Illinois United States 60153
13 Investigative Clinical Research of Indiana Indianapolis Indiana United States 46260
14 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
15 Karmanos Cancer Institute Detroit Michigan United States 48201
16 Henry Ford Health System Detroit Michigan United States 48202
17 Nebraska Methodist Hospital Omaha Nebraska United States 68114
18 Midwest Cancer Center Omaha Nebraska United States 68130
19 Urology Cancer Center, PC Omaha Nebraska United States 68130
20 Comprehensive Cancer Center Of Nevada Henderson Nevada United States 89052
21 Comprehensive Cancer Centers of Nevada Henderson Nevada United States 89074
22 Comprehensive Cancer Center Of Nevada Las Vegas Nevada United States 89128
23 Comprehensive Cancer Center of Nevada Las Vegas Nevada United States 89148
24 Hackensack University Medical Center - John Theurer Cancer Hackensack New Jersey United States 07601
25 New York Oncology Hematology, P.C. Albany New York United States 12206
26 New York Oncology Hematology, PC Albany New York United States 12208
27 Montefiore Medical Center Bronx New York United States 10467
28 New York Oncology Hematology, P.C. Clifton Park New York United States 12065
29 New York Presbyterian Hospital New York New York United States 10021
30 Columbia University Medical Center - Herbert Irving Pavilion New York New York United States 10032
31 University of Rochester Medical Center Rochester New York United States 14642
32 Wake Forest University Baptist Medical Center (WFUBMC) Winston-Salem North Carolina United States 27157
33 Cleveland Clinic Cleveland Ohio United States 44195
34 Ohio Cancer Specialists Mansfield Ohio United States 44906
35 North Coast Cancer Care, Inc Sandusky Ohio United States 44870
36 Wooster Specialty and Surgery Center Wooster Ohio United States 44691
37 St. Luke University Health Network Easton Pennsylvania United States 18045
38 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
39 University of Pittsburgh Medical Center (UPMC) Pittsburgh Pennsylvania United States 15232
40 Texas Oncology - Austin Midtown Austin Texas United States 78705
41 Texas Oncology-Central Austin Cancer Center Austin Texas United States 78731
42 Texas Oncology - South Austin Cancer Center Austin Texas United States 78745
43 Texas Oncology - Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
44 Texas Oncology - Fort Worth 12th Ave Fort Worth Texas United States 76104
45 Texas Oncology SW Fort Worth Cancer Center Fort Worth Texas United States 76132
46 Arizona Oncology Associates, PC - HAL Fort Worth Texas United States 76177
47 Comprehensive Cancer Centers of Nevada (CCCN) Fort Worth Texas United States 76177
48 Comprehensive Cancer Centers of Nevada Fort Worth Texas United States 76177
49 Nebraska Cancer Specialists (NCS) - Midwest Cancer Center Fort Worth Texas United States 76177
50 Texas Oncology - El Paso Cancer Treatment Center Fort Worth Texas United States 76177
51 Texas Oncology-El Paso Cancer Treatment Center Fort Worth Texas United States 76177
52 Texas Oncology-Garland Garland Texas United States 75042
53 Baylor College of Medicine - Baylor Clinic Houston Texas United States 77030
54 Texas Oncology - Longview Cancer Center Longview Texas United States 75601
55 Texas Oncology, P.A. Plano Texas United States 75093
56 Texas Oncology - Tyler Tyler Texas United States 75702
57 UZ Antwerpen Edegem Antwerpen Belgium 2650
58 Institut Jules Bordet Bruxelles Brussels Capital Region Belgium 1000
59 Grand Hôpital de Charleroi - Site Notre-Dame Charleroi Hainaut Belgium 6000
60 CHU Ambroise Paré Mons Hainaut Belgium 7000
61 Jessa Ziekenhuis - Campus Virga Jesse Hasselt Limburg Belgium 3500
62 CHU Dinant Godinne UCL Namur Yvoir Namur Belgium 5530
63 UZ Gent Gent Oost-Vlaanderen Belgium 9000
64 AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan Brugge West-Vlaanderen Belgium 8000
65 British Columbia Cancer Agency (BCCA) Vancouver British Columbia Canada V5Z 4E6
66 Dr. Leon Richard Oncology Centre Moncton New Brunswick Canada E1C 8X3
67 London Health Sciences Center London Ontario Canada N6A 4L6
68 Sunnybrook Toronto Ontario Canada M4N3M5
69 Masarykuv onkologicky ustav Brno Brno-město Czechia 656 53
70 FN Hradec Kralove Hradec Kralove Královéhradecký Kraj Czechia 500 05
71 Fakultni nemocnice Olomouc Olomouc Olomoucký Kraj Czechia 779 00
72 Fakultni nemocnice u sv. Anny v Brne Brno Czechia 656 91
73 Fakultni nemocnice v Motole Praha 5 Czechia 150 06
74 Herlev Hospital Herlev Capital Denmark 2730
75 Aarhus Universitetshospital Aarhus C Central Jutland Denmark 8000
76 Odense Universitetshospital Odense South Denmark Denmark 5000
77 Hopital Saint-André Bordeaux Cedex Gironde France 33075
78 CHRU de Tours - Hopital Bretonneau TOURS Tours CEDEX 1 Indre-et-Loire France 37000
79 Institut de Cancerologie de la Loire Saint-Priest-en-Jarez Loire France 42271
80 Institut de Cancérologie de l'Ouest Site Paul Papin Angers Maine-et-Loire France 49000
81 Institut de cancérologie de Lorraine Vandoeuvre Les Nancy Meurthe-et-Moselle France 54519
82 centre Oscar Lambret Lille Nord-Pas-de-Calais France 59020
83 Clinique Victor Hugo Le Mans Pays-de-la-Loire France 72000
84 Institut Paoli-Calmettes Marseille Cedex 09 France 13273
85 Chu De Poitiers Poitiers France 86021
86 ICO Saint Herblain CEDEX France 44805
87 Institut Gustave Roussy Villejuif France 94805
88 Universitätsklinikum Freiburg Freiburg Baden-Württemberg Germany 79106
89 Univesitaetsklinik Heidelberg Heidelberg Baden-Württemberg Germany 69120
90 Kliniken Nordoberpfalz AG, Klinikum Weiden Weiden Bayern Germany 92637
91 Johann Wolfgang Goethe Universität Frankfurt am Main Hessen Germany 60590
92 Evangelisches Krankenhaus Bielefeld Bielefeld Nordrhein-Westfalen Germany 33611
93 SZB Study Center University Hospital Bonn Bonn Nordrhein-Westfalen Germany D-53127
94 Uniklinik Köln Klinik und Poliklinik für Urologie Köln Nordrhein-Westfalen Germany 50937
95 Universitätsklinikum des Saarlandes Homburg Saarland Germany 66421
96 Universitätsklinikum Carl Gustav Carus Dresden Sachsen Germany 1307
97 Jena University Hospital Jena Thüringen Germany 7743
98 Universitätsklinikum Aachen Aachen Germany 52074
99 Universitätsklinikum Hamburg-Eppendorf Hamburg Germany 20246
100 Medizinische Hochschule Hannover Hannover Germany 30625
101 Universitaetsklinikum Muenster Muenster Germany 48149
102 Universität Tübingen Tübingen Germany 72076
103 Pécsi Tudományegyetem Klinikai Központ Pécs Baranya Hungary 7624
104 Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház Miskolc Borsod-Abaúj-Zemplén Hungary 3526
105 Békés Megyei Pándy Kálmán Kórház Gyula Békés Hungary 5700
106 Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo Szeged Csongrád Hungary 6720
107 Debreceni Egyetem Klinikai Központ Debrecen Hajdú-Bihar Hungary 4032
108 Szent Margit Kórház Budapest Hungary 1032
109 Magyar Honvédség Egészségügyi Központ Budapest Hungary 1062
110 Semmelweis Egyetem Budapest Hungary 1082
111 Semmelweis Egyetem Budapest Hungary 1083
112 Országos Onkológiai Intézet Budapest Hungary 1122
113 Egyesített Szent István és Szent László Kórház-Rendelőintéze Budapest Hungary H-1096
114 Somogy Megyei Kaposi Mór Oktató Kórház Kaposvár Hungary 7400
115 Markusovszky Egyetemi Oktatókórház Szombathely Hungary H-9700
116 Zala Megyei Korhaz Zalaegerszeg Hungary H-8900
117 Casa Sollievo della Sofferenza, IRCCS San Giovanni Rotondo Foggia Italy 71013
118 Irccs Irst Meldola Forli Italy 47014
119 Istituto Clinico Humanitas Rozzano, IRCCS Rozzano Milano Italy 20089
120 Usl 7 Siena - Ospedale Alta Valdelsa ASL TOSCANA SUD-EST Poggibonsi Siena Italy 53100
121 Istituto di Candiolo, IRCCS Candiolo Torino Italy 10060
122 Ospedale S.Donato, AUSL 8 di Arezzo Arezzo Italy 52100
123 Centro di Riferimento Oncologico IRCCS Aviano Italy 33081
124 AO Spedali Civili di Brescia, PO Spedali Civili Brescia Italy 25123
125 P.O. Ss. Annunziata Chieti Italy 66013
126 ASST-Istituti Ospitalieri di Cremona, AO di Cremona Cremona Italy 26100
127 AOU Careggi Firenze Italy
128 IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca Genova Italy 16132
129 Ospedale Vito Fazzi, ASL Lecce Lecce Italy 73100
130 Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy 20133
131 Ieo, Irccs Milano Italy
132 AOU Policlinico di Modena Modena Italy 41124
133 IRCCS Fondazione "Giovanni Pascale" Napoli Italy 80131
134 Istituto Oncologico Veneto IOV-IRCCS Padova Italy 35128
135 IRCCS Policlinico San Matteo Pavia Italy 27100
136 PU Campus Bio-medico di Roma Roma Italy 00128
137 Regina Elena, Istituto Nazionale dei Tumori, IFO, IRCCS Roma Italy 144
138 Azienda Ospedaliera San Camillo Forlanini Roma Italy 151
139 Azienda Ospedaliera S. Maria di Terni Terni Italy 5100
140 Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina Otwock Mazowieckie Poland 05-400
141 Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie Warszawa Mazowieckie Poland 02-781
142 MAGODENT Sp. z o.o. Szpital Onkologiczno-Kardiologiczny Warszawa Mazowieckie Poland 04-125
143 Szpital Specjalist w Brzozowie Podkarpacki Ośrodek Onkologiczny Brzozow Poland 36-200
144 COPERNICUS Podmiot Leczn. Sp z o.o.,Wojew. Centrum Onkologii Gdansk Poland 80-219
145 NZOZ Vesalius Sp. z o.o. Krakow Poland 31-216
146 Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego Wroclaw Poland 50-556
147 H.G.U. de Elche Elche Alicante Spain 03203
148 H.U.Son Espases Palma Baleares Spain 07010
149 Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol Badalona Barcelona Spain 08916
150 Institut Catalá d´Oncología (I.C.O.) L'Hospitalet De Llobregat Barcelona Spain 08907
151 C.S. Parc Taulí Sabadell Barcelona Spain 08208
152 H.U.F. Alcorcón Alcorcón Madrid Spain 28922
153 H.U.P Hierro-Majadahonda Majadahonda Madrid Spain 28222
154 C.H. de Navarra Pamplona Navarra Spain 31008
155 H.del Mar Barcelona Spain 08003
156 H.Sta.Creu i St.Pau Barcelona Spain 08025
157 H.U.Vall d'Hebrón Barcelona Spain 08035
158 H. Clinic de Barcelona Barcelona Spain 08036
159 H.U. Reina Sofía Córdoba Spain 14004
160 ICO-H.U.Dr.J.Trueta Girona Spain 17007
161 C.H. de Jaén Jaén Spain 23007
162 H.G.U. G. Marañón Madrid Spain 28007
163 H.U. Infanta Leonor Madrid Spain 28031
164 Hospital Universitario Ramón y Cajal Madrid Spain 28034
165 H.C. S.Carlos Madrid Spain 28040
166 H.U. F. Jiménez Díaz Madrid Spain 28040
167 H.U. 12 de Octubre Madrid Spain 28041
168 H.U. La Paz Madrid Spain 28046
169 H. Madrid Norte Sanchinarro Madrid Spain 28050
170 H.U. Virgen de la Victoria Málaga Spain 29010
171 H.U.V. Macarena Sevilla Spain 41009
172 F.I. Valenciano de Oncología Valencia Spain 46009
173 H.U.P.La Fe Valencia Spain 46026
174 H.U. Miguel Servet Zaragoza Spain 50009
175 Addenbrooke's Hospital Cambridge Cambridgeshire United Kingdom CB2 0QQ
176 Beatson West Of Scotland Cancer Centre Glasgow Glasgow City United Kingdom G12 0YN
177 Cheltenham General Hospital Cheltenham Gloucestershire United Kingdom GL53 7AN
178 Southampton University Hospitals Nhs Trust Southampton Hampshire United Kingdom SO16 6YD
179 East Lancashire Hospitals NHS Trust Blackburn Lancashire United Kingdom BB2 3HH
180 Lancashire Teaching Hospitals NHS Foundation Trust Preston Lancashire United Kingdom PR2 9HT
181 Royal Stroke Center Stoke-on-Trent Staffordshire United Kingdom ST4 6QG
182 The Royal Marsden NHS Foundation Trust Sutton Surrey United Kingdom SM2 5PT
183 St James's University Hospital / Leeds Teaching Hospitals Leeds United Kingdom LS9 7TF
184 The Royal Marsden NHS Foundation Trust London United Kingdom SW36JJ
185 Charing Cross Hospital London United Kingdom W6 8RF
186 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
187 Mount Vernon Cancer Care Middlesex United Kingdom HA6 2RN
188 Nottingham University Hospitals NHS Trust - City Hospital Nottingham United Kingdom NG5 1PB
189 Churchill Hospital [Oncology] Oxford United Kingdom OX3 7LJ
190 Singleton Hospital Swansea United Kingdom SA2 8QA
191 New Cross Hospital Wolverhampton United Kingdom WV10 0QP

Sponsors and Collaborators

  • AVEO Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02627963
Other Study ID Numbers:
  • AV-951-15-303
First Posted:
Dec 11, 2015
Last Update Posted:
Jan 26, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Sorafenib

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Arm/Group Description Patients randomized to this arm will receive the study drug, tivozanib hydrochloride. tivozanib hydrochloride: tivozanib hydrochloride Patients randomized to this arm will receive the comparator drug, sorafenib. Sorafenib: Sorafenib
Period Title: Overall Study
STARTED 175 175
COMPLETED 139 161
NOT COMPLETED 36 14

Baseline Characteristics

Arm/Group Title Tivozanib Hydrochloride Sorafenib Total
Arm/Group Description Patients randomized to this arm will receive the study drug, tivozanib hydrochloride. tivozanib hydrochloride: tivozanib hydrochloride Patients randomized to this arm will receive the comparator drug, sorafenib. Sorafenib: Sorafenib Total of all reporting groups
Overall Participants 175 175 350
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]
62
63
63
Sex: Female, Male (Count of Participants)
Female
49
28%
47
26.9%
96
27.4%
Male
126
72%
128
73.1%
254
72.6%
Race/Ethnicity, Customized (Count of Participants)
White
165
94.3%
167
95.4%
332
94.9%
Non-white
10
5.7%
8
4.6%
18
5.1%
Previous therapies (Count of Participants)
Two VEGFR TKIs
79
45.1%
80
45.7%
159
45.4%
Checkpoint inhibitor plus VEGFR TKI
47
26.9%
44
25.1%
91
26%
VEGFR TKI plus other systemic agent
49
28%
51
29.1%
100
28.6%
IMDC risk category (Count of Participants)
Favourable
34
19.4%
36
20.6%
70
20%
Intermediate
109
62.3%
105
60%
214
61.1%
Poor
32
18.3%
34
19.4%
66
18.9%

Outcome Measures

1. Primary Outcome
Title Progression-free Survival (PFS)
Description Progression-Free Survival (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.
Time Frame 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.

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Arm/Group Description Patients randomized to this arm will receive the study drug, tivozanib hydrochloride. tivozanib hydrochloride: tivozanib hydrochloride Patients randomized to this arm will receive the comparator drug, sorafenib. Sorafenib: Sorafenib
Measure Participants 175 175
Median (95% Confidence Interval) [Months]
5.6
3.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tivozanib Hydrochloride, Sorafenib
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.016
Comments A one-sided, log-rank test stratified for IMDC risk category and prior therapy (two VEGFR TKIs vs. a checkpoint inhibitor plus a VEGFR TKI vs. a VEGFR TKI plus any other systemic agent) at a significance level of α = 0.025 will be used.
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.56 to 0.94
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Overall Survival (OS)
Description Overall survival (OS) is defined as the time from the date of randomization to date of death due to any cause.
Time Frame Date of randomization to date of death

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Arm/Group Description Patients randomized to this arm will receive the study drug, tivozanib hydrochloride. tivozanib hydrochloride: tivozanib hydrochloride Patients randomized to this arm will receive the comparator drug, sorafenib. Sorafenib: Sorafenib
Measure Participants 175 175
Median (95% Confidence Interval) [Months]
16.4
19.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tivozanib Hydrochloride, Sorafenib
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.82
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.75 to 1.25
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Objective Response Rate (ORR)
Description Objective response rate (ORR) is defined as the percentage of subjects who have at least a 30% reduction in the sum of diameters per RECIST (Version 1.1).
Time Frame Every 8 weeks from date of randomization until disease progression

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Arm/Group Description Patients randomized to this arm will receive the study drug, tivozanib hydrochloride. tivozanib hydrochloride: tivozanib hydrochloride Patients randomized to this arm will receive the comparator drug, sorafenib. Sorafenib: Sorafenib
Measure Participants 175 175
Count of Participants [Participants]
31
17.7%
14
8%
4. Secondary Outcome
Title Duration of Response (DOR)
Description Duration of response (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.
Time Frame Assessed every 8 weeks from date of randomization until date of progression

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Arm/Group Description Patients randomized to this arm will receive the study drug, tivozanib hydrochloride. tivozanib hydrochloride: tivozanib hydrochloride Patients randomized to this arm will receive the comparator drug, sorafenib. Sorafenib: Sorafenib
Measure Participants 175 175
Median (95% Confidence Interval) [Months]
NA
5.7

Adverse Events

Time Frame From first dose to last dose plus 30 days
Adverse Event Reporting Description Serious Treatment-Emergent Adverse Events and Treatment-Emergent Adverse Events in SAF Population Reported
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Arm/Group Description Patients randomized to this arm will receive the study drug, tivozanib hydrochloride. tivozanib hydrochloride: tivozanib hydrochloride Patients randomized to this arm will receive the comparator drug, sorafenib. Sorafenib: Sorafenib
All Cause Mortality
Tivozanib Hydrochloride Sorafenib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 114/175 (65.1%) 113/175 (64.6%)
Serious Adverse Events
Tivozanib Hydrochloride Sorafenib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 75/173 (43.4%) 67/170 (39.4%)
Blood and lymphatic system disorders
Anaemia 1/173 (0.6%) 1/170 (0.6%)
Cardiac disorders
Acute coronary syndrome 1/173 (0.6%) 1/170 (0.6%)
Cardiac failure 1/173 (0.6%) 1/170 (0.6%)
Atrial fibrillation 1/173 (0.6%) 0/170 (0%)
Cardio-respiratory arrest 1/173 (0.6%) 0/170 (0%)
Myocardial infarction 0/173 (0%) 5/170 (2.9%)
Acute myocardial infarction 0/173 (0%) 2/170 (1.2%)
Coronary artery disease 0/173 (0%) 2/170 (1.2%)
Atrial flutter 0/173 (0%) 1/170 (0.6%)
Left ventricular dysfunction 0/173 (0%) 1/170 (0.6%)
Pericardial effusion 0/173 (0%) 1/170 (0.6%)
Supraventricular tachycardia 0/173 (0%) 1/170 (0.6%)
Ventricular tachycardia 0/173 (0%) 1/170 (0.6%)
Ear and labyrinth disorders
Vertigo 2/173 (1.2%) 0/170 (0%)
Endocrine disorders
Hypercalcaemia of malignancy 1/173 (0.6%) 0/170 (0%)
Gastrointestinal disorders
Vomiting 1/173 (0.6%) 3/170 (1.8%)
Abdominal pain 1/173 (0.6%) 2/170 (1.2%)
Gastrointestinal haemorrhage 1/173 (0.6%) 1/170 (0.6%)
Stomatitis 1/173 (0.6%) 1/170 (0.6%)
Intestinal obstruction 1/173 (0.6%) 0/170 (0%)
Melaena 1/173 (0.6%) 0/170 (0%)
Pancreatitis acute 1/173 (0.6%) 0/170 (0%)
Rectal haemorrhage 1/173 (0.6%) 0/170 (0%)
Anal ulcer 0/173 (0%) 1/170 (0.6%)
Constipation 0/173 (0%) 1/170 (0.6%)
Diarrhoea 0/173 (0%) 1/170 (0.6%)
Gastric haemorrhage 0/173 (0%) 1/170 (0.6%)
General disorders
Asthenia 3/173 (1.7%) 2/170 (1.2%)
Pyrexia 2/173 (1.2%) 1/170 (0.6%)
Death 1/173 (0.6%) 3/170 (1.8%)
Multiple organ dysfunction syndrome 1/173 (0.6%) 0/170 (0%)
Pain 1/173 (0.6%) 0/170 (0%)
Fatigue 0/173 (0%) 1/170 (0.6%)
General physical health deterioration 0/173 (0%) 1/170 (0.6%)
Performance status decreased 0/173 (0%) 1/170 (0.6%)
Hepatobiliary disorders
Cholangitis 1/173 (0.6%) 0/170 (0%)
Cholecystitis 1/173 (0.6%) 0/170 (0%)
Hepatic failure 1/173 (0.6%) 0/170 (0%)
Hepatobiliary disease 1/173 (0.6%) 0/170 (0%)
Hyperbilirubinaemia 1/173 (0.6%) 0/170 (0%)
Jaundice 1/173 (0.6%) 0/170 (0%)
Infections and infestations
Pneumonia 5/173 (2.9%) 5/170 (2.9%)
Urinary tract infection 3/173 (1.7%) 1/170 (0.6%)
Influenza 2/173 (1.2%) 0/170 (0%)
Appendicitis 1/173 (0.6%) 1/170 (0.6%)
Lung infection 1/173 (0.6%) 1/170 (0.6%)
Lower respiratory tract infection 1/173 (0.6%) 0/170 (0%)
Meningitis aseptic 1/173 (0.6%) 0/170 (0%)
Post procedural infection 1/173 (0.6%) 0/170 (0%)
Clostridium difficile colitis 0/173 (0%) 1/170 (0.6%)
Gastroenteritis 0/173 (0%) 1/170 (0.6%)
Lung abscess 0/173 (0%) 1/170 (0.6%)
Upper respiratory tract infection 0/173 (0%) 1/170 (0.6%)
Injury, poisoning and procedural complications
Humerus fracture 1/173 (0.6%) 0/170 (0%)
Multiple fractures 1/173 (0.6%) 0/170 (0%)
Radiation oesophagitis 1/173 (0.6%) 0/170 (0%)
Subdural haematoma 1/173 (0.6%) 0/170 (0%)
Rib fracture 0/173 (0%) 1/170 (0.6%)
Investigations
Blood creatinine increased 0/173 (0%) 1/170 (0.6%)
Metabolism and nutrition disorders
Decreased appetite 3/173 (1.7%) 1/170 (0.6%)
Hypercalcaemia 2/173 (1.2%) 0/170 (0%)
Hyponatraemia 2/173 (1.2%) 0/170 (0%)
Cachexia 1/173 (0.6%) 1/170 (0.6%)
Dehydration 1/173 (0.6%) 1/170 (0.6%)
Musculoskeletal and connective tissue disorders
Osteoarthritis 1/173 (0.6%) 0/170 (0%)
Pain in extremity 1/173 (0.6%) 0/170 (0%)
Soft tissue necrosis 1/173 (0.6%) 0/170 (0%)
Bone pain 0/173 (0%) 2/170 (1.2%)
Arthralgia 0/173 (0%) 1/170 (0.6%)
Back pain 0/173 (0%) 1/170 (0.6%)
Spinal pain 0/173 (0%) 1/170 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression 4/173 (2.3%) 4/170 (2.4%)
Prostate cancer 1/173 (0.6%) 0/170 (0%)
Tumour pain 1/173 (0.6%) 0/170 (0%)
Abdominal neoplasm 0/173 (0%) 1/170 (0.6%)
Metastases to spinal cord 0/173 (0%) 1/170 (0.6%)
Nervous system disorders
Cerebrovascular accident 4/173 (2.3%) 1/170 (0.6%)
Ischaemic stroke 2/173 (1.2%) 0/170 (0%)
Peripheral motor neuropathy 2/173 (1.2%) 0/170 (0%)
Spinal cord compression 1/173 (0.6%) 1/170 (0.6%)
Transient ischaemic attack 1/173 (0.6%) 1/170 (0.6%)
Altered state of consciousness 1/173 (0.6%) 0/170 (0%)
Brain compression 1/173 (0.6%) 0/170 (0%)
Dizziness 1/173 (0.6%) 0/170 (0%)
Paralysis 1/173 (0.6%) 0/170 (0%)
Cerebral haemorrhage 0/173 (0%) 1/170 (0.6%)
Coma 0/173 (0%) 1/170 (0.6%)
Frontal lobe epilepsy 0/173 (0%) 1/170 (0.6%)
Haemorrhage intracranial 0/173 (0%) 1/170 (0.6%)
Optic neuritis 0/173 (0%) 1/170 (0.6%)
Psychiatric disorders
Confusional state 3/173 (1.7%) 0/170 (0%)
Depression 1/173 (0.6%) 0/170 (0%)
Disorientation 1/173 (0.6%) 0/170 (0%)
Mental disorder 1/173 (0.6%) 0/170 (0%)
Renal and urinary disorders
Acute kidney injury 3/173 (1.7%) 0/170 (0%)
Renal failure 1/173 (0.6%) 2/170 (1.2%)
Haematuria 1/173 (0.6%) 0/170 (0%)
Proteinuria 0/173 (0%) 1/170 (0.6%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism 5/173 (2.9%) 0/170 (0%)
Pleural effusion 3/173 (1.7%) 1/170 (0.6%)
Dyspnoea 2/173 (1.2%) 1/170 (0.6%)
Respiratory failure 2/173 (1.2%) 1/170 (0.6%)
Acute respiratory failure 1/173 (0.6%) 0/170 (0%)
Bronchial ulceration 1/173 (0.6%) 0/170 (0%)
Chronic obstructive pulmonary disease 1/173 (0.6%) 0/170 (0%)
Haemoptysis 1/173 (0.6%) 0/170 (0%)
Laryngeal stenosis 1/173 (0.6%) 0/170 (0%)
Epistaxis 0/173 (0%) 1/170 (0.6%)
Hydrothorax 0/173 (0%) 1/170 (0.6%)
Pulmonary oedema 0/173 (0%) 1/170 (0.6%)
Respiratory arrest 0/173 (0%) 1/170 (0.6%)
Skin and subcutaneous tissue disorders
Diabetic foot 1/173 (0.6%) 0/170 (0%)
Rash 0/173 (0%) 3/170 (1.8%)
Rash maculo-papular 0/173 (0%) 2/170 (1.2%)
Palmar-plantar erythrodysaesthesia syndrome 0/173 (0%) 1/170 (0.6%)
Rash morbilliform 0/173 (0%) 1/170 (0.6%)
Toxic skin eruption 0/173 (0%) 1/170 (0.6%)
Surgical and medical procedures
Rehabilitation therapy 0/173 (0%) 1/170 (0.6%)
Vascular disorders
Hypertension 2/173 (1.2%) 0/170 (0%)
Arteriosclerosis 1/173 (0.6%) 0/170 (0%)
Deep vein thrombosis 1/173 (0.6%) 0/170 (0%)
Other (Not Including Serious) Adverse Events
Tivozanib Hydrochloride Sorafenib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 171/173 (98.8%) 170/170 (100%)
Blood and lymphatic system disorders
Anaemia 16/173 (9.2%) 23/170 (13.5%)
Endocrine disorders
Hypothyroidism 32/173 (18.5%) 13/170 (7.6%)
Gastrointestinal disorders
Diarrhoea 74/173 (42.8%) 91/170 (53.5%)
Stomatitis 36/173 (20.8%) 39/170 (22.9%)
Nausea 50/173 (28.9%) 31/170 (18.2%)
Vomiting 31/173 (17.9%) 28/170 (16.5%)
Abdominal pain 20/173 (11.6%) 18/170 (10.6%)
Abdominal pain upper 18/173 (10.4%) 12/170 (7.1%)
Constipation 19/173 (11%) 31/170 (18.2%)
Dyspepsia 15/173 (8.7%) 3/170 (1.8%)
General disorders
Fatigue 63/173 (36.4%) 42/170 (24.7%)
Asthenia 57/173 (32.9%) 40/170 (23.5%)
Oedema peripheral 16/173 (9.2%) 12/170 (7.1%)
Pyrexia 15/173 (8.7%) 19/170 (11.2%)
Infections and infestations
Nasopharyngitis 11/173 (6.4%) 1/170 (0.6%)
Urinary tract infection 9/173 (5.2%) 12/170 (7.1%)
Pneumonia 6/173 (3.5%) 10/170 (5.9%)
Investigations
Weight decreased 29/173 (16.8%) 37/170 (21.8%)
Blood thyroid stimulating hormone increased 12/173 (6.9%) 2/170 (1.2%)
Blood creatinine increased 13/173 (7.5%) 3/170 (1.8%)
Lipase increased 9/173 (5.2%) 3/170 (1.8%)
Metabolism and nutrition disorders
Decreased appetite 65/173 (37.6%) 51/170 (30%)
Hyperkalaemia 11/173 (6.4%) 5/170 (2.9%)
Hypocalcaemia 4/173 (2.3%) 10/170 (5.9%)
Musculoskeletal and connective tissue disorders
Back pain 31/173 (17.9%) 27/170 (15.9%)
Arthralgia 17/173 (9.8%) 16/170 (9.4%)
Pain in extremity 17/173 (9.8%) 11/170 (6.5%)
Muscle spasms 12/173 (6.9%) 7/170 (4.1%)
Musculoskeletal pain 9/173 (5.2%) 4/170 (2.4%)
Nervous system disorders
Dizziness 18/173 (10.4%) 8/170 (4.7%)
Headache 20/173 (11.6%) 16/170 (9.4%)
Dysgeusia 10/173 (5.8%) 8/170 (4.7%)
Renal and urinary disorders
Proteinuria 16/173 (9.2%) 7/170 (4.1%)
Respiratory, thoracic and mediastinal disorders
Dysphonia 47/173 (27.2%) 16/170 (9.4%)
Dyspnoea 26/173 (15%) 18/170 (10.6%)
Cough 37/173 (21.4%) 26/170 (15.3%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome 28/173 (16.2%) 69/170 (40.6%)
Rash 17/173 (9.8%) 44/170 (25.9%)
Dry skin 11/173 (6.4%) 9/170 (5.3%)
Alopecia 6/173 (3.5%) 37/170 (21.8%)
Erythema 3/173 (1.7%) 12/170 (7.1%)
Pruritus 4/173 (2.3%) 20/170 (11.8%)
Rash maculo-papular 1/173 (0.6%) 13/170 (7.6%)
Hyperkeratosis 1/173 (0.6%) 9/170 (5.3%)
Vascular disorders
Hypertension 73/173 (42.2%) 50/170 (29.4%)
Hypotension 9/173 (5.2%) 2/170 (1.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title AVEO Clinical Trial Office
Organization AVEO Pharmaceuticals, Inc.
Phone 857-400-0101
Email Clinical@aveooncology.com
Responsible Party:
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02627963
Other Study ID Numbers:
  • AV-951-15-303
First Posted:
Dec 11, 2015
Last Update Posted:
Jan 26, 2022
Last Verified:
Jan 1, 2022