- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02314377
Bevacizumab Therapy for Brain Arteriovenous Malformation
February 28, 2020 updated by: Daniel L. Cooke, University of California, San Francisco
Bevacizumab Therapy for brain arteriovenous malformation that is not amenable to surgical intervention.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
2
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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San Francisco, California, United States, 94143
- University of California San Francisco
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 62 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: AVM treatment with Bevacizumab
Bevacizumab infusion dose of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).
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Bevacizumab dosing of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Our primary outcome will be change in AVM volume from pre-treatment MRI.
Time Frame: 12, 26 and 52 weeks
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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.
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12, 26 and 52 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Serum VEGF levels
Time Frame: at baseline and at 12, 26 and 52 weeks
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at baseline and at 12, 26 and 52 weeks
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Urine analysis
Time Frame: at baseline and at 12, 26 and 52 weeks
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at baseline and at 12, 26 and 52 weeks
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Physical exam
Time Frame: at baseline and at 12, 26 and 52 weeks
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at baseline and at 12, 26 and 52 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Daniel Cooke, MD, UCSF Medical Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2016
Primary Completion (Actual)
December 1, 2018
Study Completion (Actual)
December 1, 2019
Study Registration Dates
First Submitted
November 25, 2014
First Submitted That Met QC Criteria
December 10, 2014
First Posted (Estimate)
December 11, 2014
Study Record Updates
Last Update Posted (Actual)
March 3, 2020
Last Update Submitted That Met QC Criteria
February 28, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Cardiovascular Abnormalities
- Neoplasms, Vascular Tissue
- Vascular Malformations
- Congenital Abnormalities
- Hemangioma
- Arteriovenous Malformations
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- DNA1052
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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