Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02314377
Recruitment Status : Recruiting
First Posted : December 11, 2014
Last Update Posted : October 31, 2018
Sponsor:
Information provided by (Responsible Party):
Daniel L. Cooke, University of California, San Francisco

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

Condition or disease Intervention/treatment Phase
Brain Arteriovenous Malformation Drug: Bevacizumab Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bevacizumab Therapy for Brain Arteriovenous Malformation
Study Start Date : June 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: AVM treatment with Bevacizumab
Bevacizumab infusion dose of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).
Drug: Bevacizumab
Bevacizumab dosing of 5mg/kg q 2 weeks for 12 weeks (2.5 mg/week).
Other Name: avastin




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Serum VEGF levels [ Time Frame: at baseline and at 12, 26 and 52 weeks ]
  2. Urine analysis [ Time Frame: at baseline and at 12, 26 and 52 weeks ]
  3. Physical exam [ Time Frame: at baseline and at 12, 26 and 52 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02314377


Contacts
Layout table for location contacts
Contact: Daniel Cooke, MD 415-353-1863

Locations
Layout table for location information
United States, California
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Daniel L Cooke, MD    415-353-1863    daniel.cooke@ucsf.edu   
Contact: Melissa Dickey, RN    415 353 1863    Melissa.Dickey@ucsf.edu   
Principal Investigator: Daniel L Cooke, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Layout table for investigator information
Principal Investigator: Daniel Cooke, MD UCSF Medical Center

Layout table for additonal information
Responsible Party: Daniel L. Cooke, Associate Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02314377     History of Changes
Other Study ID Numbers: DNA1052
First Posted: December 11, 2014    Key Record Dates
Last Update Posted: October 31, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
Layout table for MeSH terms
Congenital Abnormalities
Arteriovenous Malformations
Hemangioma
Vascular Malformations
Cardiovascular Abnormalities
Cardiovascular Diseases
Vascular Diseases
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors