Trial Outcomes & Findings for A Phase II Study of Tivozanib in Patients With Metastatic and Non-resectable Soft Tissue Sarcomas (NCT NCT01782313)
NCT ID: NCT01782313
Last Updated: 2019-09-09
Results Overview
Progression-free survival from study disease will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Committee, version 1.1 assessed using imaging scans (CT or MRI) and clinical assessment following 16 weeks of treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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", or similar definition as accurate and appropriate.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
58 participants
Primary outcome timeframe
At 16 weeks of treatment.
Results posted on
2019-09-09
Participant Flow
The study opened for accrual on February 25, 2013 with an accrual goal of up to 58 patients. The study was designed to enroll 19 patients initially and and continue to enroll up to 58 patients if 5 or more of the first 19 are progression free at 4 months. The study was closed permanently on February 4, 2015 with 58 patients enrolled.
Participant milestones
| Measure |
Treatment (Tivozanib)
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Reached First Response/Completed 2 Cycle
STARTED
|
58
|
|
Reached First Response/Completed 2 Cycle
COMPLETED
|
52
|
|
Reached First Response/Completed 2 Cycle
NOT COMPLETED
|
6
|
|
Treated Cycle 3
STARTED
|
52
|
|
Treated Cycle 3
COMPLETED
|
31
|
|
Treated Cycle 3
NOT COMPLETED
|
21
|
|
Treated Cycle 4/Reached 16 Week Response
STARTED
|
31
|
|
Treated Cycle 4/Reached 16 Week Response
COMPLETED
|
25
|
|
Treated Cycle 4/Reached 16 Week Response
NOT COMPLETED
|
6
|
|
Continued Treatment After 16 Weeks
STARTED
|
25
|
|
Continued Treatment After 16 Weeks
COMPLETED
|
18
|
|
Continued Treatment After 16 Weeks
NOT COMPLETED
|
7
|
|
Survival Follow up
STARTED
|
58
|
|
Survival Follow up
COMPLETED
|
57
|
|
Survival Follow up
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Treatment (Tivozanib)
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Reached First Response/Completed 2 Cycle
Adverse Event
|
3
|
|
Reached First Response/Completed 2 Cycle
Progressive Disease
|
3
|
|
Treated Cycle 3
Progressive Disease
|
21
|
|
Treated Cycle 4/Reached 16 Week Response
Progressive Disease
|
5
|
|
Treated Cycle 4/Reached 16 Week Response
Adverse Event
|
1
|
|
Continued Treatment After 16 Weeks
Progressive Disease
|
6
|
|
Continued Treatment After 16 Weeks
Withdrawal by Subject
|
1
|
|
Survival Follow up
Lost to Follow-up
|
1
|
Baseline Characteristics
A Phase II Study of Tivozanib in Patients With Metastatic and Non-resectable Soft Tissue Sarcomas
Baseline characteristics by cohort
| Measure |
Treatment (Tivozanib)
n=58 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
40 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
56 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
57 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
58 Participants
n=5 Participants
|
|
Prior anti-overexpress vascular endothelial growth factor (VEGF) therapy or anti-VEGF therapy naive
Prior anti-VEGF therapy
|
24 Participants
n=5 Participants
|
|
Prior anti-overexpress vascular endothelial growth factor (VEGF) therapy or anti-VEGF therapy naive
No prior anti-VEGF therapy
|
34 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At 16 weeks of treatment.Population: 3 patients were not evaluable due to withdrawal tivozanib within the first 14 days of treatment.
Progression-free survival from study disease will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Committee, version 1.1 assessed using imaging scans (CT or MRI) and clinical assessment following 16 weeks of treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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", or similar definition as accurate and appropriate.
Outcome measures
| Measure |
Treatment (Tivozanib)
n=55 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Percentage of Patients With Progression-free Survival at 16 Weeks.
|
36.4 Percentage of patients
Interval 23.7 to 49.1
|
SECONDARY outcome
Timeframe: Every 2 cycles (8 weeks) up to 2 yearsPopulation: 3 patients were not evaluable due to withdrawal tivozanib within the first 14 days of treatment.
The response to study treatment will be assessed after every 8 weeks (2 cycles) of therapy using CT or MRI scan images.Overall response rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete response (CR) = disappearance of all target lesions. Partial Response (PR), = at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Outcome measures
| Measure |
Treatment (Tivozanib)
n=55 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Response Rate Defined as Complete Response and Partial Response.
|
2 Participants
|
SECONDARY outcome
Timeframe: Every 2 cycles (8 weeks) up to 2 yearsPopulation: 3 patients were not evaluable due to withdrawal tivozanib within the first 14 days of treatment.
The clinical benefit of study treatment will be assessed after 8 weeks (2 cycles) of therapy using scanning images (CT or MRI). Clinical benefit rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR) = disappearance of all target lesions. Partial Response (PR), = at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD) = At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Outcome measures
| Measure |
Treatment (Tivozanib)
n=55 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Clinical Benefit Rate as Defined by Complete Response, Partial Response and Stable Disease.
|
32 Participants
|
SECONDARY outcome
Timeframe: Time from the first dose of study treatment up to 2 years beyond disease progressionPopulation: 3 patients were not evaluable due to withdrawal tivozanib within the first 14 days of treatment.
Patients will be followed-up with from first dose of study drug up to 2 years following the date of disease progression.
Outcome measures
| Measure |
Treatment (Tivozanib)
n=55 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Overall Survival up to 2 Years Beyond Progression
|
12.2 Months
Interval 8.1 to 16.8
|
SECONDARY outcome
Timeframe: Tissue collected during screening process, prior to first treatment and response measured until 350 days.Population: 3 patients were not evaluable due to withdrawal tivozanib within the first 14 days of treatment. Not all patients treated on study provided tissue or had sufficient tissue to be analyzed for VEGFR expression.
Tissue from biopsy will be collected during screening and proteins (VEGFR1 and VEGFR2) will be evaluated to see if there is a correlation with patient response to treatment. VERGFR = vascular endothelial growth factor receptor To determine if there was a correlation between response to Tivozanib and VEGFR expression, immunohistochemical (IHC) analysis on archival tumor tissue was performed. We performed standard IHC and applied combined intensity score (from 0 to 3) for antigen expression and proportional score of 0-3 for the cells that were positive. For antigen expression, 0 was no staining, +1 being 1-25% staining, +2 being 26-50% staining and +3 being 50% or greater staining. Number of patients with VEGFR1 expression was correlated with time patients were on treatment in days.
Outcome measures
| Measure |
Treatment (Tivozanib)
n=40 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +3 : 100 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group 0 : 0 days
|
8 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group 0 : 50 days
|
6 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group 0 : 100 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group 0 : 150 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group 0 : 200 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group 0 : 250 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group 0 : 300 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group 0 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +1 : 0 days
|
3 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +1 : 50 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +1 : 100 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +1 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +1 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +1 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +1 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +1 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +2 : 0 days
|
8 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +2 : 50 days
|
4 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +2 : 100 days
|
4 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +2 : 150 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +2 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +2 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +2 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +2 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +3 : 0 days
|
21 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +3 : 50 days
|
11 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +3 : 100 days
|
4 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +3 : 150 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +3 : 200 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +3 : 250 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +3 : 300 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR1 Group +3 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group 0 : 0 days
|
19 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group 0 : 50 days
|
11 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group 0 : 100 days
|
6 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group 0 : 150 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group 0 : 200 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group 0 : 250 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group 0 : 300 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group 0 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +1 : 0 days
|
6 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +1 : 50 days
|
4 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +1 : 100 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +1 : 150 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +1 : 200 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +1 : 250 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +1 : 300 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +1 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +2 : 0 days
|
4 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +2 : 50 days
|
3 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +2 : 100 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +2 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +2 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +2 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +2 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +2 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +3 : 0 days
|
8 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +3 : 50 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +3 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +3 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +3 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +3 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR1 and VEGFR2 Protein Expression and Time in Days on Treatment
VEGFR2 Group +3 : 350 days
|
0 participants
|
SECONDARY outcome
Timeframe: After every 4 weeks (1 cycle) until treatment discontinuation and up to a maximum of 2 years and 10 months.Population: All patients were considered to be evaluable for adverse events. Frequency of treatment related adverse events equal to or more than 10% graded to be either 1 (mild), 2 (moderate),3 (severe), 4 (life-threatening).
Toxicity will be assessed after 4 weeks (1 cycle) and every 4 weeks during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (CTCAE v4.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Outcome measures
| Measure |
Treatment (Tivozanib)
n=58 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Alkaline phosphatase increase
|
9 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Fatigue
|
28 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Hypertension
|
25 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Nausea
|
18 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Diarrhea
|
16 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Vomiting
|
9 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Hyperglycemia
|
12 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Headache
|
13 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Lymphopenia
|
11 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Anorexia
|
12 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Hoarseness
|
11 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Aspartate aminotransferase increased
|
10 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
GGT increased
|
10 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Dyspnea
|
9 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Cough
|
9 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Constipation
|
8 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Thrombocytopenia
|
8 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Myalgia
|
9 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Oral Mucositis
|
6 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Weight loss
|
7 participants
|
|
Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment During Systematic Assessment.
Hyponatremia
|
6 participants
|
POST_HOC outcome
Timeframe: Tissue collected during screening process, prior to first treatment and response measured until 350 days.Population: 3 patients were not evaluable due to withdrawal tivozanib within the first 14 days of treatment. Not all patients treated on study provided tissue or had sufficient tissue to be analyzed for VEGFR expression.
Tissue from biopsy will be collected during screening and proteins (VEGFR3) will be evaluated to see if there is a correlation with patient response to treatment. VERGFR = vascular endothelial growth factor receptor To determine if there was a correlation between response to Tivozanib and VEGFR expression, immunohistochemical (IHC) analysis on archival tumor tissue was performed. We performed standard IHC and applied combined intensity score (from 0 to 3) for antigen expression and proportional score of 0-3 for the cells that were positive. For antigen expression, 0 was no staining, +1 being 1-25% staining, +2 being 26-50% staining and +3 being 50% or greater staining. Number of patients with VEGFR1 expression was correlated with time patients were on treatment in days.
Outcome measures
| Measure |
Treatment (Tivozanib)
n=40 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group 0 : 0 days
|
26 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group 0 : 50 days
|
14 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group 0 : 100 days
|
7 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group 0 : 150 days
|
4 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group 0 : 200 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group 0 : 250 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group 0 : 300 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group 0 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +1 : 0 days
|
7 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +1 : 50 days
|
6 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +1 : 100 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +1 : 150 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +1 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +1 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +1 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +1 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +2 : 0 days
|
2 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +2 : 50 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +2 : 100 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +2 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +2 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +2 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +2 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +2 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +3 : 0 days
|
5 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +3 : 50 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +3 : 100 days
|
1 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +3 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +3 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +3 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +3 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 VEGFR3 Protein Expression and Time in Days on Treatment
VEGFR3 Group +3 : 350 days
|
0 participants
|
POST_HOC outcome
Timeframe: Tissue collected during screening process, prior to first treatment and response measured until 350 days.Population: 3 patients were not evaluable due to withdrawal tivozanib within the first 14 days of treatment. Not all patients treated on study provided tissue or had sufficient tissue to be analyzed for PDGFR expression. No patients showed PDGFR alpha +1 or +3 expression.
Tissue from biopsy will be collected during screening and proteins (PDGFR alpha and PDGFR beta) will be evaluated to see if there is a correlation with patient response to treatment. PDGFR= Platelet derived growth factor receptor To determine if there was a correlation between response to Tivozanib and PDGFR expression, immunohistochemical (IHC) analysis on archival tumor tissue was performed. We performed standard IHC and applied combined intensity score (from 0 to 3) for antigen expression and proportional score of 0-3 for the cells that were positive. For antigen expression, 0 was no staining, +1 being 1-25% staining, +2 being 26-50% staining and +3 being 50% or greater staining. Number of patients with PDGFR alpha and PDGFR beta expression was correlated with time patients were on treatment in days.
Outcome measures
| Measure |
Treatment (Tivozanib)
n=40 Participants
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group 0 : 150 days
|
5 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group 0 : 0 days
|
38 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group 0 : 50 days
|
21 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group 0 : 100 days
|
10 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group 0 : 200 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group 0 : 250 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group 0 : 300 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group 0 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group+2 : 0 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group+2 : 50 days
|
1 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group+2 : 100 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group+2 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group+2 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group+2 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group+2 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR alpha Group+2 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group 0 : 0 days
|
26 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group 0 : 50 days
|
14 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group 0 : 100 days
|
7 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group 0 : 150 days
|
4 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group 0 : 200 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group 0 : 250 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group 0 : 300 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group 0 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +1 : 0 days
|
7 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +1 : 50 days
|
6 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +1 : 100 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +1 : 200 days
|
1 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +1 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +1 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +1 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +1 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +2 : 0 days
|
2 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +2 : 50 days
|
1 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +2 : 100 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +2 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +2 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +2 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +2 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +2 : 350 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +3 : 0 days
|
5 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +3 : 50 days
|
1 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +3 : 100 days
|
1 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +3 : 150 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +3 : 200 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +3 : 250 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +3 : 300 days
|
0 participants
|
|
Number of Patients With 0-3 PDGFR Alpha and PDGFR Beta Protein Expression and Time in Days on Treatment
PDGFR beta Group +3 : 350 days
|
0 participants
|
Adverse Events
Treatment (Tivozanib)
Serious events: 26 serious events
Other events: 58 other events
Deaths: 49 deaths
Serious adverse events
| Measure |
Treatment (Tivozanib)
n=58 participants at risk
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
5.2%
3/58 • Number of events 3 • Adverse events were collected over 2 years and 10 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Cardiac disorders
Atrial Fibrillation
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Abdominal pain
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Anal hemorrhage
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Diarrhea
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Mucositis oral
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Nausea
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Blood and lymphatic system disorders
Pancytopenia
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Clinical deterioration
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Fatigue
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Death NOS
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Localized edema
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Edema limbs
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Fever
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Pain
|
6.9%
4/58 • Number of events 4 • Adverse events were collected over 2 years and 10 months
|
|
Infections and infestations
Lung infection
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Infections and infestations
Abdominal infection
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Infections and infestations
Urinary tract infection
|
5.2%
3/58 • Number of events 3 • Adverse events were collected over 2 years and 10 months
|
|
Infections and infestations
Sepsis
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Ejection fraction decreased
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Blood bilirubin increased
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Dehydration
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Musculoskeletal and connective tissue disorders
Muscle cramps
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Nervous system disorders
Stroke
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Nervous system disorders
Cognitive disturbance
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Nervous system disorders
Myelitis
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Nervous system disorders
Headache
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Nervous system disorders
Reversible posterior leukoencephalopathy syndrome
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Psychiatric disorders
Confusion
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Renal and urinary disorders
Urinary retention
|
5.2%
3/58 • Number of events 3 • Adverse events were collected over 2 years and 10 months
|
|
Renal and urinary disorders
Hydronephrosis
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Renal and urinary disorders
Urinary tract obstuction
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumorthorax
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
|
Vascular disorders
Hypertension
|
1.7%
1/58 • Number of events 1 • Adverse events were collected over 2 years and 10 months
|
Other adverse events
| Measure |
Treatment (Tivozanib)
n=58 participants at risk
Patients receive tivozanib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
tivozanib: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
15.5%
9/58 • Number of events 10 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Constipation
|
17.2%
10/58 • Number of events 10 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Diarrhea
|
32.8%
19/58 • Number of events 24 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Dyspepsia
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Mucositis oral
|
12.1%
7/58 • Number of events 9 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Nausea
|
36.2%
21/58 • Number of events 25 • Adverse events were collected over 2 years and 10 months
|
|
Blood and lymphatic system disorders
Anemia
|
32.8%
19/58 • Number of events 26 • Adverse events were collected over 2 years and 10 months
|
|
Blood and lymphatic system disorders
Leukocytosis
|
8.6%
5/58 • Number of events 5 • Adverse events were collected over 2 years and 10 months
|
|
Endocrine disorders
Hypothyroidism
|
10.3%
6/58 • Number of events 6 • Adverse events were collected over 2 years and 10 months
|
|
Endocrine disorders
Hyperthyroidism
|
10.3%
6/58 • Number of events 7 • Adverse events were collected over 2 years and 10 months
|
|
Eye disorders
Blurred vision
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Oral pain
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Stomach pain
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Gastrointestinal disorders
Vomiting
|
22.4%
13/58 • Number of events 17 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Edema - limbs
|
5.2%
3/58 • Number of events 3 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Fatigue
|
50.0%
29/58 • Number of events 38 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Fever
|
8.6%
5/58 • Number of events 9 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Gait disturbance
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Non-cardiac chest pain
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
General disorders
Pain
|
27.6%
16/58 • Number of events 20 • Adverse events were collected over 2 years and 10 months
|
|
Infections and infestations
Urinary tract infection
|
8.6%
5/58 • Number of events 5 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Activated partial thromboplastin time prolonged
|
34.5%
20/58 • Number of events 24 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Alanine aminotransferase increased
|
17.2%
10/58 • Number of events 10 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Alkaline phosphatase increased
|
27.6%
16/58 • Number of events 23 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Aspartate aminotransferase increased
|
31.0%
18/58 • Number of events 19 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Blood bilirubin increased
|
8.6%
5/58 • Number of events 9 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Creatinine increased
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Ejection fraction decreased
|
8.6%
5/58 • Number of events 5 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
GGT increased
|
27.6%
16/58 • Number of events 19 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
INR increased
|
17.2%
10/58 • Number of events 11 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Lymphocyte count decreased
|
48.3%
28/58 • Number of events 34 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Platelet count decreased
|
20.7%
12/58 • Number of events 14 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
Weight loss
|
13.8%
8/58 • Number of events 8 • Adverse events were collected over 2 years and 10 months
|
|
Investigations
White blood cell decreased
|
6.9%
4/58 • Number of events 4 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Anorexia
|
22.4%
13/58 • Number of events 16 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Dehydration
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
46.6%
27/58 • Number of events 49 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
53.4%
31/58 • Number of events 46 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
8.6%
5/58 • Number of events 6 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
6.9%
4/58 • Number of events 4 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
22.4%
13/58 • Number of events 20 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
31.0%
18/58 • Number of events 23 • Adverse events were collected over 2 years and 10 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
17.2%
10/58 • Number of events 18 • Adverse events were collected over 2 years and 10 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.2%
3/58 • Number of events 3 • Adverse events were collected over 2 years and 10 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.8%
8/58 • Number of events 8 • Adverse events were collected over 2 years and 10 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
15.5%
9/58 • Number of events 12 • Adverse events were collected over 2 years and 10 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.1%
7/58 • Number of events 13 • Adverse events were collected over 2 years and 10 months
|
|
Nervous system disorders
Dizziness
|
5.2%
3/58 • Number of events 3 • Adverse events were collected over 2 years and 10 months
|
|
Nervous system disorders
Headaches
|
25.9%
15/58 • Number of events 15 • Adverse events were collected over 2 years and 10 months
|
|
Nervous system disorders
Memory impairment
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Renal and urinary disorders
Urinary Frequency
|
6.9%
4/58 • Number of events 4 • Adverse events were collected over 2 years and 10 months
|
|
Renal and urinary disorders
Proteinuria
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.0%
11/58 • Number of events 14 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
24.1%
14/58 • Number of events 16 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
19.0%
11/58 • Number of events 12 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
5.2%
3/58 • Number of events 3 • Adverse events were collected over 2 years and 10 months
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
5.2%
3/58 • Number of events 4 • Adverse events were collected over 2 years and 10 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.4%
2/58 • Number of events 4 • Adverse events were collected over 2 years and 10 months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
|
Vascular disorders
Hypertension
|
50.0%
29/58 • Number of events 42 • Adverse events were collected over 2 years and 10 months
|
|
Vascular disorders
Hypotension
|
3.4%
2/58 • Number of events 2 • Adverse events were collected over 2 years and 10 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place