Brain Arteriovenous MalformationPhase 1NCT02314377
Bevacizumab Therapy for Brain Arteriovenous Malformation
A Phase 1 study testing Bevacizumab in people with Brain Arteriovenous Malformation, run by University of California, San Francisco at 1 site in United States.
Trial summary
Bevacizumab Therapy for brain arteriovenous malformation that is not amenable to surgical intervention. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Brain Arteriovenous Malformation
- What is being tested?
- Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to 1 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- bAVM deemed unsuitable for invasive treatment OR patient has elected to defer invasive treatment OR failed conventional therapy
- Age greater than 18 years at time of first study drug administration
- Spetzler-Martin grade III - V
- Progressive or disabling signs and symptoms as determined by the study investigators. In the case of sporadic bAVM, these would be referable to the lesion, e.g., progressive neurological deficits, refractory headaches and seizures; for HHT patients, bAVM may be asymptomatic, but patient must have one progressively symptomatic manifestation of HHT that is referable to a vascular lesion, e.g., epistaxis, GI bleeding; or another solid organ AVM
- Patients must have adequate bone marrow function (WBC > 3,000/μl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 mg/dl), adequate liver function (SGOT and bilirubin < 1.5 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) within 14 days before starting therapy
- Negative pregnancy test within 14 days of starting therapy
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- Patients must not have proteinuria at screening as demonstrated by either 1) urine protein: creatinine (UPC) ratio > 1.0 at screening, OR 2) urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible)
- Patients must not have inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg) on antihypertensive medications
- Patients must not have any prior history of hypertensive crisis or hypertensive encephalopathy
- Patients must not have New York Heart Association Grade II or greater congestive heart failure
- Patients must not have history of myocardial infarction or unstable angina within 12 months prior to study enrollment
- Patients must not have symptomatic peripheral vascular disease
- Patients must not have significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Patients must not have major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks of beginning Avastin or the anticipation of need for major surgical procedure during the course of the study
- Patients must not have core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to bevacizumab
- Patients must not have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- Patients must not have serious, non-healing wound, ulcer, or bone fracture
- Patients must not be pregnant or breast-feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of starting treatment. Effective contraception (men and women) must be used in subjects of child-bearing potential
- Patients must not be on any other experimental agents/clinical trials
- Signed informed consent
Who cannot join
- Diffuse lesion that cannot be assessed in terms of volume by cross-sectional imaging on MRI
- Inability to undergo MRI scans
- Coagulation disorders, e.g., thrombocytopenia, coagulopathy or anticoagulant therapy (Plavix and ASA is not excluded)
- Low probability to adhere to study protocol or functional impairment that could compromise safety monitoring
- Unstable medical or psychiatric illness
- Ovarian dysfunction (criteria waived if potential future to have children (e.g. post menopausal or s/p tubal ligation) limited biologically.
- Clinically significant thrombotic episode within the last 24 weeks
- Atrial fibrillation
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94143
About this study
Bevacizumab Therapy for brain arteriovenous malformation that is not amenable to surgical intervention.
Read the detailed description
Brain AVMs are relatively rare, though their potential for ICH along with the existence of effective treatments makes their diagnosis and management essential to the community. The 2-4% annual incidence of such secondary ICH creates controversy regarding treatment for asymptomatic patients. Brain AVMs thus require multidisciplinary evaluation for optimal management especially for surgical grades III - V lesions that often require some combination of embolization, microsurgery, and/or radiosurgical treatment. Currently there is no designated medical therapy for bAVM, though there is growing animal and human evidence supporting a role for bevacizumab to reduce the size of AVMs in the brain and liver, respectively. This proposal is a pilot study to assess the efficacy and safety of bevacizumab in humans with bAVMs.
- Conditions
- Brain Arteriovenous Malformation
- Being tested
- Bevacizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called avastin
Bevacizumab dosing of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).
| Study group | Role | What they receive |
|---|---|---|
| AVM treatment with Bevacizumab | Experimental | Bevacizumab infusion dose of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week). Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Our primary outcome will be change in AVM volume from pre-treatment MRI.
AVM volume will be assessed by review of standardized 1.5 mm slices in the axial plane. The contour of the vascular mass using time-of-flight MR angiography sequences will generate a cross-sectional area at each slice level. The volume will be estimated by summing the imputed volume of each slice. This is the standard method in radiation oncology used to assess bAVM volume for radiosurgery treatment planning using commercial software (Leksell GammaPlan). The source images and measurement images will be archived on a research workstation. After a baseline MR examination, follow-up MRs will be performed at 12, 26 and 52 weeks.
Measured: 12, 26 and 52 weeks
Secondary outcomes (3)
Serum VEGF levels
Measured: at baseline and at 12, 26 and 52 weeks
Urine analysis
Measured: at baseline and at 12, 26 and 52 weeks
Physical exam
Measured: at baseline and at 12, 26 and 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2014 (estimated)
- Study startJun 2016
- Primary completion1 Dec 2018
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain Arteriovenous MalformationStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel L. Cooke, University of California, San Francisco
- Investigators
- Daniel Cooke, MD, Principal investigator, UCSF Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02314377
- Sponsor's protocol ID
- DNA1052
- Status last verified
- Feb 2020
- First submitted
- 25 Nov 2014
- Last updated
- 3 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Muster R, Ko N, Smith W, Su H, Dickey MA, Nelson J, McCulloch CE, Sneed PK, Clarke JL, Saloner DA, Eisenmenger L, Kim H, Cooke DL. Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation. BMJ Neurol Open. 2021 Mar 17;3(1):e000114. doi: 10.1136/bmjno-2020-000114. eCollection 2021.
PubMed 34189463
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bevacizumab Therapy for Brain Arteriovenous Malformation
- ClinicalTrials.gov ID
- NCT02314377
- Acronym / sponsor ID
- DNA1052
- Conditions
- Brain Arteriovenous Malformation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- 1 Dec 2018 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 11 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Bevacizumab Therapy for brain arteriovenous malformation that is not amenable to surgical intervention.
Detailed description
Brain AVMs are relatively rare, though their potential for ICH along with the existence of effective treatments makes their diagnosis and management essential to the community. The 2-4% annual incidence of such secondary ICH creates controversy regarding treatment for asymptomatic patients. Brain AVMs thus require multidisciplinary evaluation for optimal management especially for surgical grades III - V lesions that often require some combination of embolization, microsurgery, and/or radiosurgical treatment. Currently there is no designated medical therapy for bAVM, though there is growing animal and human evidence supporting a role for bevacizumab to reduce the size of AVMs in the brain and liver, respectively. This proposal is a pilot study to assess the efficacy and safety of bevacizumab in humans with bAVMs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AVM treatment with Bevacizumab | Experimental | Drug: BevacizumabBevacizumab infusion dose of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week). |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- bAVM deemed unsuitable for invasive treatment OR patient has elected to defer invasive treatment OR failed conventional therapy
- Age greater than 18 years at time of first study drug administration
- Spetzler-Martin grade III - V
- Progressive or disabling signs and symptoms as determined by the study investigators. In the case of sporadic bAVM, these would be referable to the lesion, e.g., progressive neurological deficits, refractory headaches and seizures; for HHT patients, bAVM may be asymptomatic, but patient must have one progressively symptomatic manifestation of HHT that is referable to a vascular lesion, e.g., epistaxis, GI bleeding; or another solid organ AVM
- Patients must have adequate bone marrow function (WBC > 3,000/μl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 mg/dl), adequate liver function (SGOT and bilirubin < 1.5 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) within 14 days before starting therapy
Key exclusion criteria (8 listed)
- Diffuse lesion that cannot be assessed in terms of volume by cross-sectional imaging on MRI
- Inability to undergo MRI scans
- Coagulation disorders, e.g., thrombocytopenia, coagulopathy or anticoagulant therapy (Plavix and ASA is not excluded)
- Low probability to adhere to study protocol or functional impairment that could compromise safety monitoring
- Unstable medical or psychiatric illness
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 |
|---|---|---|
| BevacizumabAlso: avastinBevacizumab dosing of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week). | Drug | AVM treatment with Bevacizumab |
Primary outcome
Our primary outcome will be change in AVM volume from pre-treatment MRI.
Time frame: 12, 26 and 52 weeks
AVM volume will be assessed by review of standardized 1.5 mm slices in the axial plane. The contour of the vascular mass using time-of-flight MR angiography sequences will generate a cross-sectional area at each slice level. The volume will be estimated by summing the imputed volume of each slice. This is the standard method in radiation oncology used to assess bAVM volume for radiosurgery treatment planning using commercial software (Leksell GammaPlan). The source images and measurement images will be archived on a research workstation. After a baseline MR examination, follow-up MRs will be performed at 12, 26 and 52 weeks.
3 secondary outcomes
Serum VEGF levels
Time frame: at baseline and at 12, 26 and 52 weeks
Urine analysis
Time frame: at baseline and at 12, 26 and 52 weeks
Physical exam
Time frame: at baseline and at 12, 26 and 52 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2020.
- Derived from this study: PubMed 34189463Muster R, Ko N, Smith W, Su H, Dickey MA, Nelson J, McCulloch CE, Sneed PK, Clarke JL, Saloner DA, Eisenmenger L, Kim H, Cooke DL. Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation. BMJ Neurol Open. 2021 Mar 17;3(1):e000114. doi: 10.1136/bmjno-2020-000114. eCollection 2021.
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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.
Daniel Cooke, MD principal investigator
UCSF Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bevacizumab in people with Brain Arteriovenous Malformation, run by University of California, San Francisco 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 20 inclusion and 8 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 3 Mar 2020. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Our primary outcome will be change in AVM volume from pre-treatment MRI. (time frame: 12, 26 and 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02314377, which also lists 1 linked publication.
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 3 Mar 2020; AzTrials last refreshed its copy on 6 Nov 2026.