Tivozanib for Recurrent Glioblastoma
Primary Purpose
Glioblastoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tivozanib
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed glioblastoma that has progressed based on imaging or surgery
- Measurable disease
- No more than 3 prior chemotherapy regimens
- Must have recovered from toxicity of prior therapy. An interval of at least 3 months must have elapsed since the completion of the most recent course of radiotherapy; at least 3 weeks since last non-nitrosourea containing chemotherapy regimen or molecularly targeted agent; at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen
- Life expectancy of at least 12 weeks
- Able to tolerate MRIs
- Willing to use adequate, highly effective contraception measures while on study and for at least 45 days after the last dose of study drug
Exclusion Criteria:
- Pregnant or breastfeeding
- Major surgical procedure or significant traumatic injury within 28 days of starting therapy; or minor surgical procedure within 7 days
- Receiving other study agents
- Prior therapy with an anti-VEGF agent
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib
- Receiving any medications or substances that are inhibitors or inducers of CYP450 enzymes
- Significant cardiovascular disease
- Non-healing wound, bone fracture or skin ulcer
- Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other gastrointestinal condition with increased risk of perforation; abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
- Uncontrolled intercurrent illness
- Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
- Significant bleeding disorders within 6 months prior to administration of first dose of study drug
- Currently active second primary malignancy
- HIV positive and on combination antiretroviral therapy
- Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tivozanib
Arm Description
1.5 mg daily for 3 weeks, with 1 week off.
Outcomes
Primary Outcome Measures
Number of Patients Alive and Progression Free After 6 Months
To determine the number of patients with recurrent glioblastoma (GBM) alive and progression free 6 months (PFR6) after start of tivozanib therapy
Secondary Outcome Measures
Number of Participants With Treatment Related Serious Adverse Events
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).
Median Overall Survival
Overall survival is measured from the start of treatment until the time of death.
Median Progression-Free Survival
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.
Best RANO Criteria Response
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
Steroid Dosage
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.
Change in Tumor Volume
Change in volume of the tumor in cubic centimeters at the given time points as compared to baseline
Median Apparent Diffusion Coefficient (ADC)
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.
Median Ktrans
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)
Relative Oxygen Saturation
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.
Full Information
NCT ID
NCT01846871
First Posted
May 1, 2013
Last Updated
December 17, 2018
Sponsor
Massachusetts General Hospital
Collaborators
National Comprehensive Cancer Network
1. Study Identification
Unique Protocol Identification Number
NCT01846871
Brief Title
Tivozanib for Recurrent Glioblastoma
Official Title
A Phase II Study of Tivozanib in Recurrent Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
May 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Comprehensive Cancer Network
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the study drug tivozanib is still being studied. It also means that the FDA has not yet approved tivozanib for your type of cancer.
Tivozanib is an anti-angiogenesis medicine that fights different types of cancer by blocking the blood supply to the tumor, so that the tumor does not receive the nutrients it requires to grow.
In this research study, we are looking to see what effects, good and bad, tivozanib will have on you and your disease.
Detailed Description
If you are willing to participate in this study, you will be asked to undergo some screening tests and procedures that confirm you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out taht you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. The screening process may include the following: a medical history, mini-mental status exam, physical exam, performance status, electrocardiogram, blood tests, urine test. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.
If you take part in this research study, you will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks) during which time you will be taking the study drug once daily for 3 weeks and then no study drug for the last week of each cycle. The diary will also include special instructions for taking the study drug.
During all cycles you will have a physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking.
Standard contrast-enhanced (CE) MRI scans will be done prior to all odd-numbered study cycles. Vascular MRI scans will be done prior to start of treatment, Day 1 of treatment and prior to all even-numbered cycles. These studies will be done in the Charlestown Navy Yard.
We would like to keep track of your medical condition for up to 24 months after your last dose of study treatment. We would like to do this by calling you on the telephone once a year to see how you are doing. Keeping in touch with you and checking your condition every year helps us look at the long-term effects of the research study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tivozanib
Arm Type
Experimental
Arm Description
1.5 mg daily for 3 weeks, with 1 week off.
Intervention Type
Drug
Intervention Name(s)
Tivozanib
Other Intervention Name(s)
AV-951
Primary Outcome Measure Information:
Title
Number of Patients Alive and Progression Free After 6 Months
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
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment Related Serious Adverse Events
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
Title
Median Overall Survival
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
Title
Median Progression-Free Survival
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
Title
Best RANO Criteria Response
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
Title
Steroid Dosage
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
Title
Change in Tumor Volume
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)
Title
Median Apparent Diffusion Coefficient (ADC)
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)
Title
Median Ktrans
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)
Title
Relative Oxygen Saturation
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed glioblastoma that has progressed based on imaging or surgery
Measurable disease
No more than 3 prior chemotherapy regimens
Must have recovered from toxicity of prior therapy. An interval of at least 3 months must have elapsed since the completion of the most recent course of radiotherapy; at least 3 weeks since last non-nitrosourea containing chemotherapy regimen or molecularly targeted agent; at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen
Life expectancy of at least 12 weeks
Able to tolerate MRIs
Willing to use adequate, highly effective contraception measures while on study and for at least 45 days after the last dose of study drug
Exclusion Criteria:
Pregnant or breastfeeding
Major surgical procedure or significant traumatic injury within 28 days of starting therapy; or minor surgical procedure within 7 days
Receiving other study agents
Prior therapy with an anti-VEGF agent
History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib
Receiving any medications or substances that are inhibitors or inducers of CYP450 enzymes
Significant cardiovascular disease
Non-healing wound, bone fracture or skin ulcer
Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other gastrointestinal condition with increased risk of perforation; abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
Uncontrolled intercurrent illness
Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
Significant bleeding disorders within 6 months prior to administration of first dose of study drug
Currently active second primary malignancy
HIV positive and on combination antiretroviral therapy
Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeth Gerstner, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Tivozanib for Recurrent Glioblastoma
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