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Bevacizumab Therapy for Brain Arteriovenous Malformation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02314377
Recruitment Status : Completed
First Posted : December 11, 2014
Last Update Posted : March 3, 2020
Information provided by (Responsible Party):
Daniel L. Cooke, University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE November 25, 2014
First Posted Date  ICMJE December 11, 2014
Last Update Posted Date March 3, 2020
Study Start Date  ICMJE June 2016
Actual Primary Completion Date December 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2014)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2014)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Bevacizumab Therapy for Brain Arteriovenous Malformation
Official Title  ICMJE Bevacizumab Therapy for Brain Arteriovenous Malformation
Brief Summary 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Arteriovenous Malformation
Intervention  ICMJE Drug: Bevacizumab
Bevacizumab dosing of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).
Other Name: avastin
Study Arms  ICMJE Experimental: AVM treatment with Bevacizumab
Bevacizumab infusion dose of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).
Intervention: Drug: Bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 28, 2020)
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2014)
Actual Study Completion Date  ICMJE December 1, 2019
Actual Primary Completion Date December 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02314377
Other Study ID Numbers  ICMJE DNA1052
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daniel L. Cooke, University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniel Cooke, MD UCSF Medical Center
PRS Account University of California, San Francisco
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP