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Trial record 4 of 5 for:    TIVOZANIB | Renal Cancer | Italy

A Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced 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 : Active, not recruiting
First Posted : December 11, 2015
Results First Posted : February 20, 2020
Last Update Posted : February 2, 2021
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
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Hide 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
Arm/Group Title Tivozanib Hydrochloride Sorafenib Total
Hide 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 Number of Baseline Participants 175 175 350
Hide 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%
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide 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.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Hide 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

Overall Number of Participants Analyzed 175 175
Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(5.29 to 7.33)
3.9
(3.71 to 5.55)
Hide 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 0.016
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 [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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Hide 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

Overall Number of Participants Analyzed 175 175
Median (95% Confidence Interval)
Unit of Measure: Months
16.4
(13.4 to 22.2)
19.2
(15.0 to 24.2)
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Hide 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

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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Tivozanib Hydrochloride Sorafenib
Hide 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

Overall Number of Participants Analyzed 175 175
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(12.9 to NA)
5.7 [2] 
(5.6 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.
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
Hide 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 (%) Affected / at Risk (%)
Total   114/175 (65.14%)   113/175 (64.57%) 
Hide Serious Adverse Events
Tivozanib Hydrochloride Sorafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   75/173 (43.35%)   67/170 (39.41%) 
Blood and lymphatic system disorders     
Anaemia   1/173 (0.58%)  1/170 (0.59%) 
Cardiac disorders     
Acute coronary syndrome   1/173 (0.58%)  1/170 (0.59%) 
Cardiac failure   1/173 (0.58%)  1/170 (0.59%) 
Atrial fibrillation   1/173 (0.58%)  0/170 (0.00%) 
Cardio-respiratory arrest   1/173 (0.58%)  0/170 (0.00%) 
Myocardial infarction   0/173 (0.00%)  5/170 (2.94%) 
Acute myocardial infarction   0/173 (0.00%)  2/170 (1.18%) 
Coronary artery disease   0/173 (0.00%)  2/170 (1.18%) 
Atrial flutter   0/173 (0.00%)  1/170 (0.59%) 
Left ventricular dysfunction   0/173 (0.00%)  1/170 (0.59%) 
Pericardial effusion   0/173 (0.00%)  1/170 (0.59%) 
Supraventricular tachycardia   0/173 (0.00%)  1/170 (0.59%) 
Ventricular tachycardia   0/173 (0.00%)  1/170 (0.59%) 
Ear and labyrinth disorders     
Vertigo   2/173 (1.16%)  0/170 (0.00%) 
Endocrine disorders     
Hypercalcaemia of malignancy   1/173 (0.58%)  0/170 (0.00%) 
Gastrointestinal disorders     
Vomiting   1/173 (0.58%)  3/170 (1.76%) 
Abdominal pain   1/173 (0.58%)  2/170 (1.18%) 
Gastrointestinal haemorrhage   1/173 (0.58%)  1/170 (0.59%) 
Stomatitis   1/173 (0.58%)  1/170 (0.59%) 
Intestinal obstruction   1/173 (0.58%)  0/170 (0.00%) 
Melaena   1/173 (0.58%)  0/170 (0.00%) 
Pancreatitis acute   1/173 (0.58%)  0/170 (0.00%) 
Rectal haemorrhage   1/173 (0.58%)  0/170 (0.00%) 
Anal ulcer   0/173 (0.00%)  1/170 (0.59%) 
Constipation   0/173 (0.00%)  1/170 (0.59%) 
Diarrhoea   0/173 (0.00%)  1/170 (0.59%) 
Gastric haemorrhage   0/173 (0.00%)  1/170 (0.59%) 
General disorders     
Asthenia   3/173 (1.73%)  2/170 (1.18%) 
Pyrexia   2/173 (1.16%)  1/170 (0.59%) 
Death   1/173 (0.58%)  3/170 (1.76%) 
Multiple organ dysfunction syndrome   1/173 (0.58%)  0/170 (0.00%) 
Pain   1/173 (0.58%)  0/170 (0.00%) 
Fatigue   0/173 (0.00%)  1/170 (0.59%) 
General physical health deterioration   0/173 (0.00%)  1/170 (0.59%) 
Performance status decreased   0/173 (0.00%)  1/170 (0.59%) 
Hepatobiliary disorders     
Cholangitis   1/173 (0.58%)  0/170 (0.00%) 
Cholecystitis   1/173 (0.58%)  0/170 (0.00%) 
Hepatic failure   1/173 (0.58%)  0/170 (0.00%) 
Hepatobiliary disease   1/173 (0.58%)  0/170 (0.00%) 
Hyperbilirubinaemia   1/173 (0.58%)  0/170 (0.00%) 
Jaundice   1/173 (0.58%)  0/170 (0.00%) 
Infections and infestations     
Pneumonia   5/173 (2.89%)  5/170 (2.94%) 
Urinary tract infection   3/173 (1.73%)  1/170 (0.59%) 
Influenza   2/173 (1.16%)  0/170 (0.00%) 
Appendicitis   1/173 (0.58%)  1/170 (0.59%) 
Lung infection   1/173 (0.58%)  1/170 (0.59%) 
Lower respiratory tract infection   1/173 (0.58%)  0/170 (0.00%) 
Meningitis aseptic   1/173 (0.58%)  0/170 (0.00%) 
Post procedural infection   1/173 (0.58%)  0/170 (0.00%) 
Clostridium difficile colitis   0/173 (0.00%)  1/170 (0.59%) 
Gastroenteritis   0/173 (0.00%)  1/170 (0.59%) 
Lung abscess   0/173 (0.00%)  1/170 (0.59%) 
Upper respiratory tract infection   0/173 (0.00%)  1/170 (0.59%) 
Injury, poisoning and procedural complications     
Humerus fracture   1/173 (0.58%)  0/170 (0.00%) 
Multiple fractures   1/173 (0.58%)  0/170 (0.00%) 
Radiation oesophagitis   1/173 (0.58%)  0/170 (0.00%) 
Subdural haematoma   1/173 (0.58%)  0/170 (0.00%) 
Rib fracture   0/173 (0.00%)  1/170 (0.59%) 
Investigations     
Blood creatinine increased   0/173 (0.00%)  1/170 (0.59%) 
Metabolism and nutrition disorders     
Decreased appetite   3/173 (1.73%)  1/170 (0.59%) 
Hypercalcaemia   2/173 (1.16%)  0/170 (0.00%) 
Hyponatraemia   2/173 (1.16%)  0/170 (0.00%) 
Cachexia   1/173 (0.58%)  1/170 (0.59%) 
Dehydration   1/173 (0.58%)  1/170 (0.59%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis   1/173 (0.58%)  0/170 (0.00%) 
Pain in extremity   1/173 (0.58%)  0/170 (0.00%) 
Soft tissue necrosis   1/173 (0.58%)  0/170 (0.00%) 
Bone pain   0/173 (0.00%)  2/170 (1.18%) 
Arthralgia   0/173 (0.00%)  1/170 (0.59%) 
Back pain   0/173 (0.00%)  1/170 (0.59%) 
Spinal pain   0/173 (0.00%)  1/170 (0.59%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm progression   4/173 (2.31%)  4/170 (2.35%) 
Prostate cancer   1/173 (0.58%)  0/170 (0.00%) 
Tumour pain   1/173 (0.58%)  0/170 (0.00%) 
Abdominal neoplasm   0/173 (0.00%)  1/170 (0.59%) 
Metastases to spinal cord   0/173 (0.00%)  1/170 (0.59%) 
Nervous system disorders     
Cerebrovascular accident   4/173 (2.31%)  1/170 (0.59%) 
Ischaemic stroke   2/173 (1.16%)  0/170 (0.00%) 
Peripheral motor neuropathy   2/173 (1.16%)  0/170 (0.00%) 
Spinal cord compression   1/173 (0.58%)  1/170 (0.59%) 
Transient ischaemic attack   1/173 (0.58%)  1/170 (0.59%) 
Altered state of consciousness   1/173 (0.58%)  0/170 (0.00%) 
Brain compression   1/173 (0.58%)  0/170 (0.00%) 
Dizziness   1/173 (0.58%)  0/170 (0.00%) 
Paralysis   1/173 (0.58%)  0/170 (0.00%) 
Cerebral haemorrhage   0/173 (0.00%)  1/170 (0.59%) 
Coma   0/173 (0.00%)  1/170 (0.59%) 
Frontal lobe epilepsy   0/173 (0.00%)  1/170 (0.59%) 
Haemorrhage intracranial   0/173 (0.00%)  1/170 (0.59%) 
Optic neuritis   0/173 (0.00%)  1/170 (0.59%) 
Psychiatric disorders     
Confusional state   3/173 (1.73%)  0/170 (0.00%) 
Depression   1/173 (0.58%)  0/170 (0.00%) 
Disorientation   1/173 (0.58%)  0/170 (0.00%) 
Mental disorder   1/173 (0.58%)  0/170 (0.00%) 
Renal and urinary disorders     
Acute kidney injury   3/173 (1.73%)  0/170 (0.00%) 
Renal failure   1/173 (0.58%)  2/170 (1.18%) 
Haematuria   1/173 (0.58%)  0/170 (0.00%) 
Proteinuria   0/173 (0.00%)  1/170 (0.59%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism   5/173 (2.89%)  0/170 (0.00%) 
Pleural effusion   3/173 (1.73%)  1/170 (0.59%) 
Dyspnoea   2/173 (1.16%)  1/170 (0.59%) 
Respiratory failure   2/173 (1.16%)  1/170 (0.59%) 
Acute respiratory failure   1/173 (0.58%)  0/170 (0.00%) 
Bronchial ulceration   1/173 (0.58%)  0/170 (0.00%) 
Chronic obstructive pulmonary disease   1/173 (0.58%)  0/170 (0.00%) 
Haemoptysis   1/173 (0.58%)  0/170 (0.00%) 
Laryngeal stenosis   1/173 (0.58%)  0/170 (0.00%) 
Epistaxis   0/173 (0.00%)  1/170 (0.59%) 
Hydrothorax   0/173 (0.00%)  1/170 (0.59%) 
Pulmonary oedema   0/173 (0.00%)  1/170 (0.59%) 
Respiratory arrest   0/173 (0.00%)  1/170 (0.59%) 
Skin and subcutaneous tissue disorders     
Diabetic foot   1/173 (0.58%)  0/170 (0.00%) 
Rash   0/173 (0.00%)  3/170 (1.76%) 
Rash maculo-papular   0/173 (0.00%)  2/170 (1.18%) 
Palmar-plantar erythrodysaesthesia syndrome   0/173 (0.00%)  1/170 (0.59%) 
Rash morbilliform   0/173 (0.00%)  1/170 (0.59%) 
Toxic skin eruption   0/173 (0.00%)  1/170 (0.59%) 
Surgical and medical procedures     
Rehabilitation therapy   0/173 (0.00%)  1/170 (0.59%) 
Vascular disorders     
Hypertension   2/173 (1.16%)  0/170 (0.00%) 
Arteriosclerosis   1/173 (0.58%)  0/170 (0.00%) 
Deep vein thrombosis   1/173 (0.58%)  0/170 (0.00%) 
Indicates events were collected by systematic assessment
Hide 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   16/173 (9.25%)  23/170 (13.53%) 
Endocrine disorders     
Hypothyroidism   32/173 (18.50%)  13/170 (7.65%) 
Gastrointestinal disorders     
Diarrhoea   74/173 (42.77%)  91/170 (53.53%) 
Stomatitis   36/173 (20.81%)  39/170 (22.94%) 
Nausea   50/173 (28.90%)  31/170 (18.24%) 
Vomiting   31/173 (17.92%)  28/170 (16.47%) 
Abdominal pain   20/173 (11.56%)  18/170 (10.59%) 
Abdominal pain upper   18/173 (10.40%)  12/170 (7.06%) 
Constipation   19/173 (10.98%)  31/170 (18.24%) 
Dyspepsia   15/173 (8.67%)  3/170 (1.76%) 
General disorders     
Fatigue   63/173 (36.42%)  42/170 (24.71%) 
Asthenia   57/173 (32.95%)  40/170 (23.53%) 
Oedema peripheral   16/173 (9.25%)  12/170 (7.06%) 
Pyrexia   15/173 (8.67%)  19/170 (11.18%) 
Infections and infestations     
Nasopharyngitis   11/173 (6.36%)  1/170 (0.59%) 
Urinary tract infection   9/173 (5.20%)  12/170 (7.06%) 
Pneumonia   6/173 (3.47%)  10/170 (5.88%) 
Investigations     
Weight decreased   29/173 (16.76%)  37/170 (21.76%) 
Blood thyroid stimulating hormone increased   12/173 (6.94%)  2/170 (1.18%) 
Blood creatinine increased   13/173 (7.51%)  3/170 (1.76%) 
Lipase increased   9/173 (5.20%)  3/170 (1.76%) 
Metabolism and nutrition disorders     
Decreased appetite   65/173 (37.57%)  51/170 (30.00%) 
Hyperkalaemia   11/173 (6.36%)  5/170 (2.94%) 
Hypocalcaemia   4/173 (2.31%)  10/170 (5.88%) 
Musculoskeletal and connective tissue disorders     
Back pain   31/173 (17.92%)  27/170 (15.88%) 
Arthralgia   17/173 (9.83%)  16/170 (9.41%) 
Pain in extremity   17/173 (9.83%)  11/170 (6.47%) 
Muscle spasms   12/173 (6.94%)  7/170 (4.12%) 
Musculoskeletal pain   9/173 (5.20%)  4/170 (2.35%) 
Nervous system disorders     
Dizziness   18/173 (10.40%)  8/170 (4.71%) 
Headache   20/173 (11.56%)  16/170 (9.41%) 
Dysgeusia   10/173 (5.78%)  8/170 (4.71%) 
Renal and urinary disorders     
Proteinuria   16/173 (9.25%)  7/170 (4.12%) 
Respiratory, thoracic and mediastinal disorders     
Dysphonia   47/173 (27.17%)  16/170 (9.41%) 
Dyspnoea   26/173 (15.03%)  18/170 (10.59%) 
Cough   37/173 (21.39%)  26/170 (15.29%) 
Skin and subcutaneous tissue disorders     
Palmar-plantar erythrodysaesthesia syndrome   28/173 (16.18%)  69/170 (40.59%) 
Rash   17/173 (9.83%)  44/170 (25.88%) 
Dry skin   11/173 (6.36%)  9/170 (5.29%) 
Alopecia   6/173 (3.47%)  37/170 (21.76%) 
Erythema   3/173 (1.73%)  12/170 (7.06%) 
Pruritus   4/173 (2.31%)  20/170 (11.76%) 
Rash maculo-papular   1/173 (0.58%)  13/170 (7.65%) 
Hyperkeratosis   1/173 (0.58%)  9/170 (5.29%) 
Vascular disorders     
Hypertension   73/173 (42.20%)  50/170 (29.41%) 
Hypotension   9/173 (5.20%)  2/170 (1.18%) 
Indicates events were collected by systematic assessment
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: Chief Medical Officer
Organization: AVEO Pharmaceuticals, Inc.
Phone: 617-588-1960
EMail: Clinical@aveooncology.com
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: February 2, 2021