Bevacizumab Therapy for Brain Arteriovenous Malformation

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02314377
• Date of registration: 25/11/2014
• Prospective Registration: Yes
• Primary sponsor: University of California, San Francisco
• Public title: Bevacizumab Therapy for Brain Arteriovenous Malformation
• Scientific title: Bevacizumab Therapy for Brain Arteriovenous Malformation
• Date of first enrolment: June 2016
• Target sample size: 2
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02314377
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Daniel Cooke, MD
• Affiliation: UCSF Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- 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

Exclusion Criteria:

- 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



Age minimum: 18 Years
Age maximum: 64 Years
Gender: All

Health Condition(s) or Problem(s) studied

Brain Arteriovenous Malformation

Intervention(s)

Drug: Bevacizumab

Primary Outcome(s)

Our primary outcome will be change in AVM volume from pre-treatment MRI. [Time Frame: 12, 26 and 52 weeks]

Secondary Outcome(s)

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]

Serum VEGF levels [Time Frame: at baseline and at 12, 26 and 52 weeks]

Secondary ID(s)

DNA1052

Source(s) of Monetary Support

Please refer to primary and secondary sponsors