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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02627963

Recruitment Status : Completed

First Posted : December 11, 2015

Results First Posted : February 20, 2020

Last Update Posted : July 18, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

AVEO Pharmaceuticals, Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Carcinoma, Renal Cell
Interventions	Drug: Tivozanib hydrochloride Drug: Sorafenib
Enrollment	350

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 350 participants were randomised and 343 were treated.


Arm/Group Title	Tivozanib Hydrochloride	Sorafenib
Arm/Group Description	Participants randomized to this arm...	Participants randomized to this arm...
Arm/Group Description	Participants randomized to this arm received the study drug, tivozanib hydrochloride.	Participants randomized to this arm received the comparator drug, sorafenib.
Period Title: Overall Study
Started	175	175
Completed	173	169
Not Completed	2	6
Reason Not Completed
Randomized but not treated	2	6

Baseline Characteristics

Arm/Group Title		Tivozanib Hydrochloride	Sorafenib	Total
Arm/Group Description		Participants randomized to this arm...	Participants randomized to this arm...	Total of all reporting groups
Arm/Group Description		Participants randomized to this arm received the study drug, tivozanib hydrochloride.	Participants randomized to this arm received the comparator drug, sorafenib.	Total of all reporting groups
Overall Number of Baseline Participants		175	175	350
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	175 participants	175 participants	350 participants
		62 (34 to 88)	63 (30 to 90)	63 (30 to 90)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	175 participants	175 participants	350 participants
	Female	49 28.0%	47 26.9%	96 27.4%
	Male	126 72.0%	128 73.1%	254 72.6%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
Race	Number Analyzed	175 participants	175 participants	350 participants
	White	165 94.3%	167 95.4%	332 94.9%
	Non-white	10 5.7%	8 4.6%	18 5.1%
Previous therapies Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	175 participants	175 participants	350 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 26.0%
	VEGFR TKI plus other systemic agent	49 28.0%	51 29.1%	100 28.6%
IMDC risk category Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	175 participants	175 participants	350 participants
	Favourable	34 19.4%	36 20.6%	70 20.0%
	Intermediate	109 62.3%	105 60.0%	214 61.1%
	Poor	32 18.3%	34 19.4%	66 18.9%

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival (PFS)
Description	The PFS, as assessed by a blinded independent radiological review (IRR...
Description	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.
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 (up to approximately 5 years)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population included all randomized participants.


Arm/Group Title	Tivozanib Hydrochloride	Sorafenib
Arm/Group Description:	Participants randomized to this arm...	Participants randomized to this arm...
Arm/Group Description:	Participants randomized to this arm received the study drug, tivozanib hydrochloride.	Participants randomized to this arm received the comparator drug, sorafenib.
Overall Number of Participants Analyzed	175	175
Median (95% Confidence Interval) Unit of Measure: Months
	5.59 (5.29 to 7.33)	3.88 (3.71 to 5.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tivozanib Hydrochloride, Sorafenib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0165
	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 was used.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95% 0.56 to 0.94
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Survival (OS)
Description	The OS is defined as the time from the date of randomization to date o...
Description	The 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 (up to approximately 5 years)

Outcome Measure Data

Analysis Population Description

ITT Population


Arm/Group Title	Tivozanib Hydrochloride	Sorafenib
Arm/Group Description:	Participants randomized to this arm...	Participants randomized to this arm...
Arm/Group Description:	Participants randomized to this arm received the study drug, tivozanib hydrochloride.	Participants randomized to this arm received the comparator drug, sorafenib.
Overall Number of Participants Analyzed	175	175
Median (95% Confidence Interval) Unit of Measure: Months
	16.39 (13.44 to 22.21)	19.15 (14.95 to 24.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tivozanib Hydrochloride, Sorafenib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8174
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95% 0.75 to 1.25
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Objective Response Rate (ORR)
Description	The ORR is defined as the percentage of participants who have at least...
Description	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).
Time Frame	Every 8 weeks from date of randomization until disease progression (up to approximately 5 years)

Outcome Measure Data

Analysis Population Description

ITT Population


Arm/Group Title	Tivozanib Hydrochloride	Sorafenib
Arm/Group Description:	Participants randomized to this arm...	Participants randomized to this arm...
Arm/Group Description:	Participants randomized to this arm received the study drug, tivozanib hydrochloride.	Participants randomized to this arm received the comparator drug, sorafenib.
Overall Number of Participants Analyzed	175	175
Measure Type: Count of Participants Unit of Measure: Participants
	31 17.7%	14 8.0%

4.Secondary Outcome


Title	Duration of Response (DOR)
Description	The DOR is defined as the time from the first documentation of objecti...
Description	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.
Time Frame	Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years)

Outcome Measure Data

Analysis Population Description

ITT Population


Arm/Group Title	Tivozanib Hydrochloride	Sorafenib
Arm/Group Description:	Participants randomized to this arm...	Participants randomized to this arm...
Arm/Group Description:	Participants randomized to this arm received the study drug, tivozanib hydrochloride.	Participants randomized to this arm received the comparator drug, sorafenib.
Overall Number of Participants Analyzed	175	175
Median (95% Confidence Interval) Unit of Measure: Months
	NA ^[1] (12.91 to NA)	5.65 ^[2] (5.55 to NA)

[1]

The median and upper limit of the 95% confidence interval were not calculable because an insufficient number of participants reached the event.

[2]

The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event.

Adverse Events

Time Frame	From first dose to last dose plus 30 days (up to approximately 5 years)
Adverse Event Reporting Description	Serious treatment-emergent adverse events and other (non-serious) treatment-emergent adverse events in Safety Population (all participants who received at least 1 dose of study drug) are reported.

Arm/Group Title	Tivozanib Hydrochloride	Sorafenib
Arm/Group Description	Participants randomized to this arm...	Participants randomized to this arm...
Arm/Group Description	Participants randomized to this arm received the study drug, tivozanib hydrochloride.	Participants randomized to this arm received the comparator drug, sorafenib.
All-Cause Mortality
	Tivozanib Hydrochloride	Sorafenib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	114/175 (65.14%)	113/175 (64.57%)
Serious Adverse Events Serious Adverse Events
	Tivozanib Hydrochloride	Sorafenib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	81/173 (46.82%)	67/170 (39.41%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/173 (0.58%)	1/170 (0.59%)
Thrombocytopenia ^† 1	1/173 (0.58%)	0/170 (0.00%)
Cardiac disorders
Acute coronary syndrome ^† 1	1/173 (0.58%)	1/170 (0.59%)
Cardiac failure ^† 1	1/173 (0.58%)	1/170 (0.59%)
Atrial fibrillation ^† 1	1/173 (0.58%)	0/170 (0.00%)
Cardio-respiratory arrest ^† 1	1/173 (0.58%)	0/170 (0.00%)
Myocardial infarction ^† 1	1/173 (0.58%)	5/170 (2.94%)
Acute myocardial infarction ^† 1	0/173 (0.00%)	2/170 (1.18%)
Coronary artery disease ^† 1	0/173 (0.00%)	2/170 (1.18%)
Atrial flutter ^† 1	0/173 (0.00%)	1/170 (0.59%)
Left ventricular dysfunction ^† 1	0/173 (0.00%)	1/170 (0.59%)
Pericardial effusion ^† 1	0/173 (0.00%)	1/170 (0.59%)
Supraventricular tachycardia ^† 1	0/173 (0.00%)	1/170 (0.59%)
Ventricular tachycardia ^† 1	0/173 (0.00%)	1/170 (0.59%)
Cardiac arrest ^† 1	1/173 (0.58%)	0/170 (0.00%)
Ear and labyrinth disorders
Vertigo ^† 1	2/173 (1.16%)	0/170 (0.00%)
Endocrine disorders
Hypercalcaemia of malignancy ^† 1	2/173 (1.16%)	0/170 (0.00%)
Gastrointestinal disorders
Vomiting ^† 1	1/173 (0.58%)	3/170 (1.76%)
Abdominal pain ^† 1	1/173 (0.58%)	2/170 (1.18%)
Gastrointestinal haemorrhage ^† 1	1/173 (0.58%)	1/170 (0.59%)
Stomatitis ^† 1	1/173 (0.58%)	1/170 (0.59%)
Intestinal obstruction ^† 1	1/173 (0.58%)	0/170 (0.00%)
Melaena ^† 1	1/173 (0.58%)	0/170 (0.00%)
Pancreatitis acute ^† 1	2/173 (1.16%)	0/170 (0.00%)
Rectal haemorrhage ^† 1	1/173 (0.58%)	0/170 (0.00%)
Anal ulcer ^† 1	0/173 (0.00%)	1/170 (0.59%)
Constipation ^† 1	0/173 (0.00%)	1/170 (0.59%)
Diarrhoea ^† 1	0/173 (0.00%)	1/170 (0.59%)
Gastric haemorrhage ^† 1	0/173 (0.00%)	1/170 (0.59%)
General disorders
Asthenia ^† 1	3/173 (1.73%)	2/170 (1.18%)
Pyrexia ^† 1	2/173 (1.16%)	1/170 (0.59%)
Death ^† 1	1/173 (0.58%)	3/170 (1.76%)
Multiple organ dysfunction syndrome ^† 1	1/173 (0.58%)	0/170 (0.00%)
Pain ^† 1	1/173 (0.58%)	0/170 (0.00%)
Fatigue ^† 1	0/173 (0.00%)	1/170 (0.59%)
General physical health deterioration ^† 1	0/173 (0.00%)	1/170 (0.59%)
Performance status decreased ^† 1	0/173 (0.00%)	1/170 (0.59%)
Hepatobiliary disorders
Cholangitis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Cholecystitis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Hepatic failure ^† 1	1/173 (0.58%)	0/170 (0.00%)
Hepatobiliary disease ^† 1	1/173 (0.58%)	0/170 (0.00%)
Hyperbilirubinaemia ^† 1	1/173 (0.58%)	0/170 (0.00%)
Jaundice ^† 1	1/173 (0.58%)	0/170 (0.00%)
Infections and infestations
Pneumonia ^† 1	6/173 (3.47%)	6/170 (3.53%)
Urinary tract infection ^† 1	3/173 (1.73%)	1/170 (0.59%)
Influenza ^† 1	2/173 (1.16%)	0/170 (0.00%)
Appendicitis ^† 1	1/173 (0.58%)	1/170 (0.59%)
Lower respiratory tract infection ^† 1	1/173 (0.58%)	0/170 (0.00%)
Meningitis aseptic ^† 1	1/173 (0.58%)	0/170 (0.00%)
Post procedural infection ^† 1	1/173 (0.58%)	0/170 (0.00%)
Clostridium difficile colitis ^† 1	0/173 (0.00%)	1/170 (0.59%)
Gastroenteritis ^† 1	0/173 (0.00%)	1/170 (0.59%)
Lung abscess ^† 1	0/173 (0.00%)	1/170 (0.59%)
Upper respiratory tract infection ^† 1	0/173 (0.00%)	1/170 (0.59%)
Injury, poisoning and procedural complications
Humerus fracture ^† 1	1/173 (0.58%)	0/170 (0.00%)
Multiple fractures ^† 1	1/173 (0.58%)	0/170 (0.00%)
Radiation oesophagitis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Subdural haematoma ^† 1	1/173 (0.58%)	0/170 (0.00%)
Rib fracture ^† 1	0/173 (0.00%)	1/170 (0.59%)
Head injury ^† 1	1/173 (0.58%)	0/170 (0.00%)
Investigations
Blood creatinine increased ^† 1	0/173 (0.00%)	1/170 (0.59%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	3/173 (1.73%)	1/170 (0.59%)
Hypercalcaemia ^† 1	2/173 (1.16%)	0/170 (0.00%)
Hyponatraemia ^† 1	2/173 (1.16%)	0/170 (0.00%)
Cachexia ^† 1	1/173 (0.58%)	1/170 (0.59%)
Dehydration ^† 1	1/173 (0.58%)	1/170 (0.59%)
Musculoskeletal and connective tissue disorders
Osteoarthritis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Pain in extremity ^† 1	1/173 (0.58%)	0/170 (0.00%)
Soft tissue necrosis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Bone pain ^† 1	0/173 (0.00%)	2/170 (1.18%)
Arthralgia ^† 1	0/173 (0.00%)	1/170 (0.59%)
Back pain ^† 1	0/173 (0.00%)	1/170 (0.59%)
Spinal pain ^† 1	0/173 (0.00%)	1/170 (0.59%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression ^† 1	4/173 (2.31%)	4/170 (2.35%)
Prostate cancer ^† 1	2/173 (1.16%)	0/170 (0.00%)
Tumour pain ^† 1	1/173 (0.58%)	0/170 (0.00%)
Abdominal neoplasm ^† 1	0/173 (0.00%)	1/170 (0.59%)
Metastases to spinal cord ^† 1	0/173 (0.00%)	1/170 (0.59%)
Nervous system disorders
Cerebrovascular accident ^† 1	4/173 (2.31%)	1/170 (0.59%)
Ischaemic stroke ^† 1	2/173 (1.16%)	0/170 (0.00%)
Peripheral motor neuropathy ^† 1	2/173 (1.16%)	0/170 (0.00%)
Spinal cord compression ^† 1	1/173 (0.58%)	1/170 (0.59%)
Transient ischaemic attack ^† 1	1/173 (0.58%)	1/170 (0.59%)
Altered state of consciousness ^† 1	1/173 (0.58%)	0/170 (0.00%)
Brain compression ^† 1	1/173 (0.58%)	0/170 (0.00%)
Dizziness ^† 1	1/173 (0.58%)	0/170 (0.00%)
Paralysis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Cerebral haemorrhage ^† 1	0/173 (0.00%)	1/170 (0.59%)
Coma ^† 1	0/173 (0.00%)	1/170 (0.59%)
Frontal lobe epilepsy ^† 1	0/173 (0.00%)	1/170 (0.59%)
Haemorrhage intracranial ^† 1	0/173 (0.00%)	1/170 (0.59%)
Optic neuritis ^† 1	0/173 (0.00%)	1/170 (0.59%)
Headache ^† 1	1/173 (0.58%)	0/170 (0.00%)
Seizure ^† 1	1/173 (0.58%)	0/170 (0.00%)
Psychiatric disorders
Confusional state ^† 1	3/173 (1.73%)	0/170 (0.00%)
Depression ^† 1	1/173 (0.58%)	0/170 (0.00%)
Disorientation ^† 1	1/173 (0.58%)	0/170 (0.00%)
Mental disorder ^† 1	1/173 (0.58%)	0/170 (0.00%)
Renal and urinary disorders
Acute kidney injury ^† 1	3/173 (1.73%)	0/170 (0.00%)
Renal failure ^† 1	1/173 (0.58%)	2/170 (1.18%)
Haematuria ^† 1	1/173 (0.58%)	0/170 (0.00%)
Proteinuria ^† 1	0/173 (0.00%)	1/170 (0.59%)
Renal impairment ^† 1	1/173 (0.58%)	0/170 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism ^† 1	6/173 (3.47%)	0/170 (0.00%)
Pleural effusion ^† 1	3/173 (1.73%)	1/170 (0.59%)
Dyspnoea ^† 1	3/173 (1.73%)	1/170 (0.59%)
Respiratory failure ^† 1	2/173 (1.16%)	1/170 (0.59%)
Acute respiratory failure ^† 1	1/173 (0.58%)	0/170 (0.00%)
Bronchial ulceration ^† 1	1/173 (0.58%)	0/170 (0.00%)
Chronic obstructive pulmonary disease ^† 1	1/173 (0.58%)	0/170 (0.00%)
Haemoptysis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Laryngeal stenosis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Epistaxis ^† 1	0/173 (0.00%)	1/170 (0.59%)
Hydrothorax ^† 1	0/173 (0.00%)	1/170 (0.59%)
Pulmonary oedema ^† 1	0/173 (0.00%)	1/170 (0.59%)
Respiratory arrest ^† 1	0/173 (0.00%)	1/170 (0.59%)
Skin and subcutaneous tissue disorders
Diabetic foot ^† 1	1/173 (0.58%)	0/170 (0.00%)
Rash ^† 1	0/173 (0.00%)	3/170 (1.76%)
Rash maculo-papular ^† 1	0/173 (0.00%)	2/170 (1.18%)
Palmar-plantar erythrodysaesthesia syndrome ^† 1	0/173 (0.00%)	1/170 (0.59%)
Rash morbilliform ^† 1	0/173 (0.00%)	1/170 (0.59%)
Toxic skin eruption ^† 1	0/173 (0.00%)	1/170 (0.59%)
Surgical and medical procedures
Rehabilitation therapy ^† 1	0/173 (0.00%)	1/170 (0.59%)
Vascular disorders
Hypertension ^† 1	2/173 (1.16%)	0/170 (0.00%)
Arteriosclerosis ^† 1	1/173 (0.58%)	0/170 (0.00%)
Deep vein thrombosis ^† 1	1/173 (0.58%)	0/170 (0.00%)
1 Term from vocabulary, MedDRA 19.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Tivozanib Hydrochloride	Sorafenib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	171/173 (98.84%)	170/170 (100.00%)
Blood and lymphatic system disorders
Anaemia ^† 1	17/173 (9.83%)	23/170 (13.53%)
Endocrine disorders
Hypothyroidism ^† 1	31/173 (17.92%)	13/170 (7.65%)
Gastrointestinal disorders
Diarrhoea ^† 1	74/173 (42.77%)	91/170 (53.53%)
Stomatitis ^† 1	36/173 (20.81%)	38/170 (22.35%)
Nausea ^† 1	51/173 (29.48%)	31/170 (18.24%)
Vomiting ^† 1	31/173 (17.92%)	25/170 (14.71%)
Abdominal pain ^† 1	21/173 (12.14%)	16/170 (9.41%)
Abdominal pain upper ^† 1	18/173 (10.40%)	12/170 (7.06%)
Constipation ^† 1	19/173 (10.98%)	31/170 (18.24%)
Dyspepsia ^† 1	16/173 (9.25%)	3/170 (1.76%)
Gastrooesophageal reflux disease ^† 1	9/173 (5.20%)	1/170 (0.59%)
General disorders
Fatigue ^† 1	64/173 (36.99%)	41/170 (24.12%)
Asthenia ^† 1	56/173 (32.37%)	40/170 (23.53%)
Oedema peripheral ^† 1	16/173 (9.25%)	12/170 (7.06%)
Pyrexia ^† 1	13/173 (7.51%)	18/170 (10.59%)
Infections and infestations
Nasopharyngitis ^† 1	12/173 (6.94%)	1/170 (0.59%)
Urinary tract infection ^† 1	7/173 (4.05%)	11/170 (6.47%)
Investigations
Weight decreased ^† 1	30/173 (17.34%)	37/170 (21.76%)
Blood thyroid stimulating hormone increased ^† 1	12/173 (6.94%)	2/170 (1.18%)
Blood creatinine increased ^† 1	13/173 (7.51%)	2/170 (1.18%)
Lipase increased ^† 1	9/173 (5.20%)	4/170 (2.35%)
Aspartate aminotransferase increased ^† 1	9/173 (5.20%)	3/170 (1.76%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	68/173 (39.31%)	51/170 (30.00%)
Hyperkalaemia ^† 1	12/173 (6.94%)	6/170 (3.53%)
Hypocalcaemia ^† 1	4/173 (2.31%)	10/170 (5.88%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	32/173 (18.50%)	26/170 (15.29%)
Arthralgia ^† 1	18/173 (10.40%)	15/170 (8.82%)
Pain in extremity ^† 1	18/173 (10.40%)	11/170 (6.47%)
Muscle spasms ^† 1	12/173 (6.94%)	7/170 (4.12%)
Musculoskeletal pain ^† 1	9/173 (5.20%)	4/170 (2.35%)
Nervous system disorders
Dizziness ^† 1	17/173 (9.83%)	8/170 (4.71%)
Headache ^† 1	20/173 (11.56%)	16/170 (9.41%)
Dysgeusia ^† 1	10/173 (5.78%)	8/170 (4.71%)
Renal and urinary disorders
Proteinuria ^† 1	17/173 (9.83%)	6/170 (3.53%)
Respiratory, thoracic and mediastinal disorders
Dysphonia ^† 1	47/173 (27.17%)	16/170 (9.41%)
Dyspnoea ^† 1	25/173 (14.45%)	17/170 (10.00%)
Cough ^† 1	38/173 (21.97%)	26/170 (15.29%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome ^† 1	28/173 (16.18%)	69/170 (40.59%)
Rash ^† 1	17/173 (9.83%)	42/170 (24.71%)
Dry skin ^† 1	11/173 (6.36%)	9/170 (5.29%)
Alopecia ^† 1	6/173 (3.47%)	37/170 (21.76%)
Erythema ^† 1	3/173 (1.73%)	12/170 (7.06%)
Pruritus ^† 1	4/173 (2.31%)	20/170 (11.76%)
Rash maculo-papular ^† 1	1/173 (0.58%)	11/170 (6.47%)
Hyperkeratosis ^† 1	1/173 (0.58%)	9/170 (5.29%)
Vascular disorders
Hypertension ^† 1	73/173 (42.20%)	51/170 (30.00%)
Hypotension ^† 1	9/173 (5.20%)	2/170 (1.18%)
1 Term from vocabulary, MedDRA 19.1 † Indicates events were collected by systematic assessment

Limitations and 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

Layout table for Results Point of Contact information

Name/Title:	AVEO Clinical Trial Office
Organization:	AVEO Pharmaceuticals, Inc.
Phone:	857-400-0101
EMail:	Clinical@aveooncology.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

Layout table for additonal information

Responsible Party:	AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT02627963
Other Study ID Numbers:	AV-951-15-303
First Submitted:	December 9, 2015
First Posted:	December 11, 2015
Results First Submitted:	January 16, 2020
Results First Posted:	February 20, 2020
Last Update Posted:	July 18, 2023

To Top