GlioblastomaPhase 2NCT01846871
Tivozanib for Recurrent Glioblastoma
A Phase 2 study testing Tivozanib in people with Glioblastoma, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Tivozanib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to May 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Phase II Study of Tivozanib in Recurrent Glioblastoma
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.
Read the 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.
- Conditions
- Glioblastoma
- Being tested
- Tivozanib
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TivozanibDrug
Also called AV-951
| Study group | Role | What they receive |
|---|---|---|
| Tivozanib | Experimental | 1.5 mg daily for 3 weeks, with 1 week off. Receives: Drug: Tivozanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Secondary outcomes (9)
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).
Measured: From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months
Median Overall Survival
Overall survival is measured from the start of treatment until the time of death.
Measured: From the start of treatment until the time of death, median duration of approximately 8 months
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.
Measured: From the start of treatment until death or progression, median duration of approximately 2 months
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
Measured: 2 years
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.
Measured: 2 years
Change in Tumor Volume
Change in volume of the tumor in cubic centimeters at the given time points as compared to baseline
Measured: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
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.
Measured: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
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)
Measured: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
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.
Measured: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startJun 2013
- Primary completionSep 2014
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Responsible party
- Principal investigator, Elizabeth R. Gerstner, MD, Massachusetts General Hospital
- Investigators
- Elizabeth Gerstner, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01846871
- Sponsor's protocol ID
- 13-069
- Status last verified
- Dec 2018
- First submitted
- 1 May 2013
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Tivozanib in Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT01846871
- Acronym / sponsor ID
- 13-069
- Conditions
- Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Study start
- Jun 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 3 May 2013 (estimated)
- Results
- Posted 8 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tivozanib | Experimental | Drug: Tivozanib1.5 mg daily for 3 weeks, with 1 week off. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TivozanibAlso: AV-951 | Drug | Tivozanib |
Primary outcome
Number of Patients Alive and Progression Free After 6 Months
Time frame: 6 months
To determine the number of patients with recurrent glioblastoma (GBM) alive and progression free 6 months (PFR6) after start of tivozanib therapy
9 secondary outcomes
Number of Participants With Treatment Related Serious Adverse Events
Time frame: From the start of treatment until disease progression, unacceptable toxicity, or death; median duration of approximately 2 months
Median Overall Survival
Time frame: From the start of treatment until the time of death, median duration of approximately 8 months
Median Progression-Free Survival
Time frame: From the start of treatment until death or progression, median duration of approximately 2 months
Best RANO Criteria Response
Time frame: 2 years
Steroid Dosage
Time frame: 2 years
Change in Tumor Volume
Time frame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Median Apparent Diffusion Coefficient (ADC)
Time frame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Median Ktrans
Time frame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Relative Oxygen Saturation
Time frame: Baseline, Cycle 1 day 2, pre-cycle 2, pre-cycle 3 (1 cycle= 4 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth Gerstner, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tivozanib in people with Glioblastoma, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Alive and Progression Free After 6 Months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019; AzTrials last refreshed its copy on 6 Nov 2026.