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Tivozanib for Recurrent Glioblastoma

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ClinicalTrials.gov Identifier: NCT01846871
Recruitment Status : Completed
First Posted : May 3, 2013
Results First Posted : January 8, 2019
Last Update Posted : January 8, 2019
Sponsor:
Collaborator:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Elizabeth R. Gerstner, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma
Intervention Drug: Tivozanib
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tivozanib
Hide Arm/Group Description

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

Period Title: Overall Study
Started 10
Completed 10
Not Completed 0
Arm/Group Title Tivozanib
Hide Arm/Group Description

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants
62
(51 to 74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
6
  60.0%
Male
4
  40.0%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 10 participants
10
 100.0%
1.Primary Outcome
Title Number of Patients Alive and Progression Free After 6 Months
Hide Description To determine the number of patients with recurrent glioblastoma (GBM) alive and progression free 6 months (PFR6) after start of tivozanib therapy
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
1
  10.0%
2.Secondary Outcome
Title Number of Participants With Treatment Related Serious Adverse Events
Hide Description The number of participants with serious adverse events deemed possibly, probably, or definitely related to treatment. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4).
Time Frame From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Secondary Outcome
Title Median Overall Survival
Hide Description Overall survival is measured from the start of treatment until the time of death.
Time Frame From the start of treatment until the time of death, median duration of approximately 8 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: Months
8.1
(5.2 to 12.5)
4.Secondary Outcome
Title Median Progression-Free Survival
Hide Description

Progression free survival is measured as the amount of time from the start of treatment until the time of death or disease progression. Progressive disease was assessed using MacDonald Criteria

Progressive disease: Progressive neurologic abnormalities not explained by causes unrelated to tumor 40 progression (example: anti-epileptic drug or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the volume of the tumor by MRI scan. If neurologic status deteriorates on a stable or increasing dose of corticosteroids, or if new lesions appear on serial MRI scans, this will also be considered PD.

Time Frame From the start of treatment until death or progression, median duration of approximately 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: Months
2.3
(1.5 to 4)
5.Secondary Outcome
Title Best RANO Criteria Response
Hide Description

Best response as assessed by Response Assessment in Neuro-Oncology (RANO) criteria.

Complete response

  • disappearance of all enhancing disease
  • sustained for at least 4 weeks
  • stable/improved non-enhancing FLAIR/T2W lesions
  • no new lesions
  • no corticosteroids
  • clinically stable/improved

Partial response >50% or more decrease of all measurable enhancing lesions

  • sustained for at least 4 weeks
  • no progression of non-measurable disease
  • stable/improved non-enhancing FLAIR/T2W lesions
  • no new lesions
  • stable/reduced corticosteroids
  • clinically stable/improved

Stable disease

  • does not qualify for complete response, partial response or progression
  • stable non-enhancing FLAIR/T2W lesions
  • stable or reduced corticosteroids
  • clinically stable

Progression >25% or more increase in enhancing lesions despite stable/increasing steroid dose

  • increase in non-enhancing FLAIR/T2W lesions, not attributable to other non-tumor causes
  • any new lesion
  • Clinical deterioration
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
Complete response
1
  10.0%
Partial response
1
  10.0%
Stable disease
4
  40.0%
Progressive disease
4
  40.0%
6.Secondary Outcome
Title Steroid Dosage
Hide Description The number of participants on steroids at baseline and the number of participants that increased or decreased their use of steroids during the course of treatment. Participants that required an increase and decrease in steroid use over the course of treatment were counted in both categories.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: participants
On steroids at baseline 4
Decreased dosage 3
Increased dosage 4
No change 4
7.Secondary Outcome
Title Change in Tumor Volume
Hide Description Change in volume of the tumor in cubic centimeters at the given time points as compared to baseline
Time Frame Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Measurements were not available for all participants at pre-cycle 2 and pre-cycle 3
Arm/Group Title Tivozanib (Baseline) Tivozanib (Cycle 1 Day 2) Tivozanib (Pre-cycle 2) Tivozanib (Pre-cycle 3)
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

1.5 mg daily for 3 weeks, with 1 week off.
1.5 mg daily for 3 weeks, with 1 week off.
1.5 mg daily for 3 weeks, with 1 week off.
Overall Number of Participants Analyzed 10 10 9 8
Median (Inter-Quartile Range)
Unit of Measure: Cubic Centimeters
17.37
(5.18 to 31.11)
-2.012
(-6.08 to -0.79)
-2.75
(-5.68 to 3.19)
-3.53
(-18.28 to 1.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tivozanib (Pre-cycle 3)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Median Apparent Diffusion Coefficient (ADC)
Hide Description Change in the the median ADC value from baseline at the given timepoints. Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue.
Time Frame Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib (Baseline) Tivozanib (Cycle 1 Day 2) Tivozanib (Pre-cycle 2) Tivozanib (Pre-cycle 3)
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

1.5 mg daily for 3 weeks, with 1 week off.
1.5 mg daily for 3 weeks, with 1 week off.
1.5 mg daily for 3 weeks, with 1 week off.
Overall Number of Participants Analyzed 10 10 10 10
Median (Inter-Quartile Range)
Unit of Measure: mm2/s
0.0013
(0.0011 to 0.0015)
-0.00009
(-0.00014 to -0.00005)
-0.00024
(-0.00032 to -0.00011)
-0.00023
(-0.0003 to -0.00004)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tivozanib (Baseline), Tivozanib (Pre-cycle 3)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
9.Secondary Outcome
Title Median Ktrans
Hide Description Change in the the median Ktrans value from baseline at the given time points. The volume transfer constant (Ktrans) reflects the efflux rate of gadolinium contrast from blood plasma into the tissue extravascular extracellular space (EES)
Time Frame Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tivozanib (Baseline) Tivozanib (Cycle 1 Day 2) Tivozanib (Pre-cycle 2) Tivozanib (Pre-cycle 3)
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

1.5 mg daily for 3 weeks, with 1 week off.
1.5 mg daily for 3 weeks, with 1 week off.
1.5 mg daily for 3 weeks, with 1 week off.
Overall Number of Participants Analyzed 10 10 10 10
Median (Inter-Quartile Range)
Unit of Measure: mL/min/100 mL
0.032
(0.026 to 0.054)
-0.01468
(-0.025 to -0.010)
-0.024
(-0.032 to -0.022)
-0.030
(-0.045 to -0.022)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tivozanib (Baseline), Tivozanib (Pre-cycle 3)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
10.Secondary Outcome
Title Relative Oxygen Saturation
Hide Description The change in relative O2 saturation from baseline to the given time points. Oxygen saturation is a relative measure of the concentration of oxygen that is dissolved or carried in a given medium as a proportion of the maximal concentration that can be dissolved in that medium.
Time Frame Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
One participants was not available for assessment for the cycle 1 day 2 measurement
Arm/Group Title Tivozanib (Baseline) Tivozanib (Cycle 1 Day 2) Tivozanib (Pre-cycle 2) Tivozanib (Pre-cycle 3)
Hide Arm/Group Description:

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

1.5 mg daily for 3 weeks, with 1 week off.
1.5 mg daily for 3 weeks, with 1 week off.
1.5 mg daily for 3 weeks, with 1 week off.
Overall Number of Participants Analyzed 10 9 10 10
Median (Inter-Quartile Range)
Unit of Measure: proportion of possible O2 concentration
0.64
(0.55 to 0.68)
-0.057
(-0.11 to -0.00003)
-0.0041
(-0.060 to 0.063)
-0.097
(-0.12 to -0.017)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tivozanib (Baseline), Tivozanib (Pre-cycle 3)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tivozanib
Hide Arm/Group Description

1.5 mg daily for 3 weeks, with 1 week off.

Tivozanib

All-Cause Mortality
Tivozanib
Affected / at Risk (%)
Total   0/10 (0.00%)    
Hide Serious Adverse Events
Tivozanib
Affected / at Risk (%) # Events
Total   2/10 (20.00%)    
Gastrointestinal disorders   
Colonic perforation  1  1/10 (10.00%)  1
Nervous system disorders   
Seizure  1  2/10 (20.00%)  2
Edema cerebral  1  1/10 (10.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tivozanib
Affected / at Risk (%) # Events
Total   9/10 (90.00%)    
Blood and lymphatic system disorders   
Anemia  1  2/10 (20.00%)  3
Ear and labyrinth disorders   
Ear and labyrinth disorders - Other, cerumen in right ear  1  1/10 (10.00%)  1
Ear and labyrinth disorders - Other, hearing loss in right ear  1  1/10 (10.00%)  1
Ear and labyrinth disorders - Other, Intermittent hearing loss  1  1/10 (10.00%)  1
Vertigo  1  1/10 (10.00%)  1
Eye disorders   
Eye disorders - Other, Hemanopsia  1  1/10 (10.00%)  1
Eye disorders - Other, Retro Orbital pressure  1  1/10 (10.00%)  1
Gastrointestinal disorders   
Diarrhea  1  1/10 (10.00%)  2
Mucositis oral  1  2/10 (20.00%)  3
Nausea  1  2/10 (20.00%)  2
General disorders   
Fatigue  1  7/10 (70.00%)  7
Gait disturbance  1  1/10 (10.00%)  1
Non-cardiac chest pain  1  1/10 (10.00%)  1
Infections and infestations   
Paronychia  1  1/10 (10.00%)  1
Skin infection  1  1/10 (10.00%)  1
Investigations   
Alanine aminotransferase increased  1  1/10 (10.00%)  1
Alkaline phosphatase increased  1  2/10 (20.00%)  3
Aspartate aminotransferase increased  1  1/10 (10.00%)  1
Investigations - Other, SGOT elevated  1  1/10 (10.00%)  1
Investigations - Other, SGPT elevated  1  1/10 (10.00%)  1
Lymphocyte count decreased  1  3/10 (30.00%)  4
Platelet count decreased  1  2/10 (20.00%)  2
White blood cell decreased  1  4/10 (40.00%)  5
Metabolism and nutrition disorders   
Anorexia  1  1/10 (10.00%)  1
Hyperglycemia  1  1/10 (10.00%)  1
Hypokalemia  1  2/10 (20.00%)  4
Hypophosphatemia  1  2/10 (20.00%)  2
Musculoskeletal and connective tissue disorders   
Muscle weakness left-sided  1  1/10 (10.00%)  1
Muscle weakness lower limb  1  1/10 (10.00%)  1
Muscle weakness right-sided  1  1/10 (10.00%)  1
Nervous system disorders   
Abducens nerve disorder  1  1/10 (10.00%)  1
Ataxia  1  1/10 (10.00%)  1
Cognitive disturbance  1  2/10 (20.00%)  2
Dizziness  1  1/10 (10.00%)  1
Headache  1  4/10 (40.00%)  4
Nervous system disorders - Other, Altered Coordination (right)  1  1/10 (10.00%)  1
Nervous system disorders - Other, Cognitive Dysfunction  1  1/10 (10.00%)  1
Nervous system disorders - Other, numbness right limbs  1  1/10 (10.00%)  1
Nervous system disorders - Other, Speech impairment  1  1/10 (10.00%)  1
Nystagmus  1  1/10 (10.00%)  1
Pyramidal tract syndrome  1  1/10 (10.00%)  1
Seizure  1  4/10 (40.00%)  4
Psychiatric disorders   
Anxiety  1  2/10 (20.00%)  2
Confusion  1  3/10 (30.00%)  3
Depression  1  2/10 (20.00%)  2
Renal and urinary disorders   
Proteinuria  1  1/10 (10.00%)  1
Urinary urgency  1  1/10 (10.00%)  1
Respiratory, thoracic and mediastinal disorders   
Hiccups  1  1/10 (10.00%)  1
Hoarseness  1  1/10 (10.00%)  1
Voice alteration  1  1/10 (10.00%)  1
Skin and subcutaneous tissue disorders   
Hyperhidrosis  1  1/10 (10.00%)  1
Palmar-plantar erythrodysesthesia syndrome  1  1/10 (10.00%)  1
Skin ulceration  1  1/10 (10.00%)  1
Vascular disorders   
Hypertension  1  4/10 (40.00%)  8
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Elizabeth Gerstner
Organization: Massachusetts General Hospital
Phone: 617-724-8770
EMail: EGERSTNER@mgh.harvard.edu
Layout table for additonal information
Responsible Party: Elizabeth R. Gerstner, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01846871    
Other Study ID Numbers: 13-069
First Submitted: May 1, 2013
First Posted: May 3, 2013
Results First Submitted: December 17, 2018
Results First Posted: January 8, 2019
Last Update Posted: January 8, 2019