Bevacizumab Therapy for Brain Arteriovenous Malformation

NCT02314377 | Completed Phase 1 DMC

• 1 other identifier: DNA1052
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Brain Arteriovenous Malformation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Serum VEGF levels

  at baseline and at 12, 26 and 52 weeks

• Urine analysis

  at baseline and at 12, 26 and 52 weeks

• Physical exam

  at baseline and at 12, 26 and 52 weeks

Study Arms (1)

AVM treatment with Bevacizumab

EXPERIMENTAL

Bevacizumab infusion dose of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

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

Also known as: avastin

AVM treatment with Bevacizumab

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• 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.

  PMID: 34189463 DERIVED

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Daniel Cooke, MD

  UCSF Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 25, 2014
• First Posted: December 11, 2014
• Study Start: June 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: March 3, 2020

Record last verified: 2020-02

Locations

US (1)