Bevacizumab Therapy for Brain Arteriovenous Malformation

Brain Arteriovenous Malformation Clinical Trial

Official title:

Bevacizumab Therapy for Brain Arteriovenous Malformation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02314377
• Other study ID #: DNA1052
• Status: Completed
• Phase: Phase 1
• Start date: June 2016
• Est. completion date: December 1, 2019

Study information

• Verified date: February 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Bevacizumab Therapy for brain arteriovenous malformation that is not amenable to surgical intervention.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: December 1, 2019
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Arteriovenous Malformations
• Brain Arteriovenous Malformation
• Congenital Abnormalities
• Hemangioma

Intervention

Drug:
• Bevacizumab
Bevacizumab dosing of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).

Locations

Country	Name	City	State
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12, 26 and 52 weeks
Secondary	Serum VEGF levels		at baseline and at 12, 26 and 52 weeks
Secondary	Urine analysis		at baseline and at 12, 26 and 52 weeks
Secondary	Physical exam		at baseline and at 12, 26 and 52 weeks