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Trial registered on ANZCTR


Registration number
ACTRN12622000812796
Ethics application status
Approved
Date submitted
27/05/2022
Date registered
9/06/2022
Date last updated
23/02/2024
Date data sharing statement initially provided
9/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Pre-surgical embolisation with a novel embolic agent, the Distal Penetrating Embolic System (DPE), for participants with hypervascular extra-axial brain tumours
Scientific title
First in Human Feasibility Study of Pre-Surgical Embolisation of Hypervascular Extra-axial Brain Tumours with the Arsenal Medical Distal Penetrating Embolic System (DPE) to evaluate initial Safety and Performance.
Secondary ID [1] 307232 0
Sponsor Trial Number: EMBO-01
Universal Trial Number (UTN)
U1111-1278-2466
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypervascular extra-axial brain tumour 326481 0
Brain Cancer 326482 0
Condition category
Condition code
Cancer 323751 323751 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will have their hypervascular, extra-axial brain tumour embolised with a novel embolic agent, the DPE, in a single procedure performed by a board-certified neurointerventional radiologist prior to having the tumour surgically removed. The embolisation procedure will be done in an operating room and is expected to take about 2 hours. Before the procedure starts, baseline computed tomography (CT) imaging is done to take pictures of the blood vessels in the brain that supply the brain tumour. The participant is anesthetised for the embolisation procedure. A catheter (a thin, flexible tube) is inserted into a small incision in the inner thigh or wrist and advanced through the blood vessels into the brain. During this time contrast dye will be injected into the catheter and x-ray images (digital subtractive angiography) are taken. Once the catheter is placed at the vessel which needs to be embolised, the DPE is injected until the material fills the blood vessel and stops the blood flow. The study doctor may treat more than one target vessel in order to stop or reduce blood flow to the tumour. X-ray images (digital subtractive angiography) will be taken of the embolised blood vessels. At the end of the procedure CT imaging is repeated to record the placement of the embolic material.
A clinical specialist from the Sponsor who is a technical expert on the DPE will attend the embolisation procedure and make sure the protocol is being followed and all the information about the procedure is recorded according to the protocol. The CT and X-ray images from the procedure will be reviewed by an Imaging Core Lab to make sure the embolisation procedure was successful in placing the DPE where it was needed to stop the blood flow, and that no DPE was placed where it was not needed.
The tumour will then be removed in a surgical procedure no sooner than 12 hours after the end of the embolisation procedure and no later than 7 days after the end of the embolisation procedure. The investigational procedure is the pre-operative embolisation; surgical removal of the tumor is done by a neurosurgeon according to hospital standard of care.
Intervention code [1] 323674 0
Treatment: Devices
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331508 0
The primary safety endpoint is freedom from device related disabling stroke or neurological death within 30 days of the embolisation procedure as adjudicated by an independent physician adjudicator (IPA).
The study doctor will record any adverse events that occur during the study. The IPA will review the adverse events and the medical records to determine if a device-related stroke or neurological death occurred.
Timepoint [1] 331508 0
30 days post-embolisation
Primary outcome [2] 331509 0
The primary feasibility endpoint is defined as the successful injection of DPE into the targeted vessel(s) supplying the tumour, resulting in complete occlusion of the targeted vessel(s) at or distal to the point of embolysate injection.
The primary feasibility endpoint will be assessed by the Imaging Core Lab based on the digital subtractive angiography.
Timepoint [2] 331509 0
Immediately post-embolisation.
Secondary outcome [1] 410112 0
Percent tumour devascularisation as determined by the Imaging Core Lab from the digital subtractive angiography.
Timepoint [1] 410112 0
Pre-embolisation and immediately post-embolisation.
Secondary outcome [2] 410113 0
Anatomical description (location) of each target artery catheterised and embolised, as assessed by review of procedural notes and verified by the digital subtractive angiograms.
Timepoint [2] 410113 0
Within 24 hours post-embolisation.
Secondary outcome [3] 410114 0
Degree of occlusion of each embolised target vessel, as assessed by the Imaging Core Lab based on the digital subtractive angiography.
Timepoint [3] 410114 0
Pre-embolisation and immediately post-embolisation.
Secondary outcome [4] 410115 0
Intraoperative blood loss (estimated volume) during surgical procedure to remove the tumour. This information is being captured because pre-operative embolisation may reduce blood loss during the tumour removal surgery. The surgeon estimates blood loss visually based on the amount of blood on the surgical sponges.
Timepoint [4] 410115 0
During the surgical removal of the tumour
Secondary outcome [5] 410116 0
Transfused blood volume (units of blood) as assessed by medical record review. This information is being recorded since pre-operative embolisation of the tumour may reduce blood loss and the need for blood transfusions during and after the surgery to remove the tumour.
Timepoint [5] 410116 0
Any blood transfusions given during the surgery to remove the tumour through hospital discharge will be recorded.
Secondary outcome [6] 410117 0
Total surgical time for the operation to remove the brain tumour, It is defined as the time elapsed from the initial incision to the final closure of the incision and is assessed by audit of the operation reports. This information is being recorded because pre-operative embolisation may reduce the surgical time needed to remove the tumour.
Timepoint [6] 410117 0
During the surgical procedure to remove the tumour.
Secondary outcome [7] 410118 0
Tumour Resection Time. This is defined as the time the surgeon begins the tumour removal to the time the tumour is removed or surgeon determines the resection procedure is complete (if unable to remove/resect tumour completely). Tumour resection time will be assessed by an audit of the operation reports.
Timepoint [7] 410118 0
During the surgical procedure to remove the tumour.
Secondary outcome [8] 410119 0
Modified Rankin score (mRS) is a validated questionnaire designed to assess degree of neurological disability.
Timepoint [8] 410119 0
Screening Visit, Baseline Visit (pre embolisation and within 24 hours post embolisation), Surgery (pre-surgery and within 24 hours post surgery), the 30 day follow-up visit post embolisation and the 90 day follow up visit post embolisation.
Secondary outcome [9] 410120 0
NIH Stroke Scale. This is a validated questionnaire to quantify the presence of neurological deficits before the embolisation procedure and prior to the surgical procedure
Timepoint [9] 410120 0
Within 24 hours before the embolisation procedure and within 24 hours before the surgical procedure to remove the tumor
Secondary outcome [10] 410121 0
Presence of non-target embolisation. This assessment will be done by an Imaging Core Lab based on CT imaging done prior to the embolisation procedure as compared to post embolisation procedure. Either cone beam CT or Multidetector CT is acceptable.
Timepoint [10] 410121 0
Pre-embolisation and post-embolisation (within 24 hours of the embolisation procedure).
Secondary outcome [11] 410122 0
Extent of surgical resection as determined by the surgeon on the 5-point Simpson scale. This assessment is being done as pre-operative embolisation may make it easier for the surgeon to do a more complete resection.
Timepoint [11] 410122 0
During surgery for removal of the tumour.
Secondary outcome [12] 410123 0
Histopathology of resected tumour to identify the presence of inflammation. This is an optional assessment that will be done by hospital pathologists, if done, Histopathology will be done in accordance with site standard histopathology protocols and reports.
Timepoint [12] 410123 0
Post surgical removal of the tumour
Secondary outcome [13] 410307 0
Time of embolysate injection for each target artery catheterised and embolised, as assessed by review of procedural notes and verified by the digital subtractive angiograms, which are time stamped.
Timepoint [13] 410307 0
Within 24 hours post-embolisation.
Secondary outcome [14] 410308 0
Volume of embolysate injection for each artery catheterised and embolised, as assessed by review of procedural notes.
Timepoint [14] 410308 0
Within 24 hours post-embolisation
Secondary outcome [15] 410309 0
Histopathology of resected tumour to identify the presence of necrosis. This is an optional assessment that will be done by hospital pathologists, if done, Histopathology will be done in accordance with site standard histopathology protocols and reports.
Timepoint [15] 410309 0
Post surgical removal of the tumour
Secondary outcome [16] 410310 0
Histopathology of resected tumour to identify the distribution of the DPE embolic material. This is an optional assessment that will be done by hospital pathologists, if done, Histopathology will be done in accordance with site standard histopathology protocols and reports.
Timepoint [16] 410310 0
Post surgical removal of the tumour

Eligibility
Key inclusion criteria
Screening Inclusion Criteria:
• Participant whose age is between 18 and 80 years;
• Participant whose baseline mRS score is less than or equal to 2;
• Contrast enhancing extra-axial supratentorial brain tumour measuring between 2.5 cm and 6 cm in the greatest diameter;
• Participant planned for pre-operative embolisation followed by neurological assessment, and subsequent surgical resection under a separate general anesthesia protocol within the next 7 days;
• Participant understands the nature of the procedure, consents to participation in the study and provides a signed informed consent form;
• Participant (woman of child-bearing potential) with a current negative pregnancy test who has agreed to an effective method of contraception throughout the study;
• Participant is willing to return to or call the investigational site for 30-day and 90-day follow-ups.
Baseline Inclusion Criteria:
• Digital subtractive angiography (DSA) demonstrates a hypervascular tumour blush supplied by branches of the middle meningeal artery which both originates from the external carotid artery and is amenable to catheterisation with a standard microcatheter
• A negative pregnancy test is required at baseline for a woman of child-bearing potential
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Screening Exclusion Criteria:
• Tumours originating from the skull base except lateral sphenoid wing
• Participant who is breastfeeding
• Participant with life expectancy of less than 1 year
• Prior embolisation, radiation therapy, or surgical treatment of the tumour
• Participants with renal impairment that the investigator assesses could be at risk for contrast induced nephropathy
• Participant with a life-threatening allergy to radiographic contrast (unless treatment for allergy is tolerated or can be managed medically)
• Participant is allergic to any of the materials used in the DPE device
Participant who is currently participating or planning to participate within 3 months in another non-observational clinical research study
Baseline Exclusion Criteria:
• Digital subtractive angiography (DSA) demonstrates vasculature not amenable to catheterisation or embolisation including high-risk anastomoses with eloquent arteries

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The EMBO-01 study is a prospective, multi-center, first in human clinical study. This single-arm, open-label evaluation will enroll up to 10 participants at up to 6 sites in Australia and New Zealand to evaluate the early safety and feasibility of the Arsenal Medical Distal Penetrating Embolic (DPE) for the pre-operative embolisation of hypervascular extra-axial brain tumours.

The study is considered an early feasibility study, and as such no control arm is included and no hypothesis is utilised for statistical testing. The sample size of ten participants will be used to evaluate early safety and feasibility only.

The primary safety endpoint of this study is freedom from device related disabling stroke or neurological death within 30 days of the embolisation procedure as adjudicated by an independent physician adjudicator (IPA). Since this is an early feasibility study, safety assessments are important and appropriate measurements. A DMC is being utilised to ensure review of safety data at periodic points during study enrollment and to recommend if the study should be continued, revised or closed.

The primary feasibility endpoint is defined as the successful injection of DPE into the targeted vessel(s) supplying the tumour, resulting in complete occlusion of the targeted vessel(s) at or distal to the point of embolysate injection. Vessel occlusion will be determined on the immediate post-embolisation angiogram. This endpoint is appropriate given that the study is an early feasibility study. Additional endpoints are more quantitative and include the percent devascularisation achieved with the DPE embolic and assessments associated with the surgical removal of the tumour, including blood loss and time for surgical tumour removal.

As a first in human study, the choice of the number of participants is not statistically based. The enrollment of 10 participants is supported by evidence of the safety of DPE for use in the embolisation of hypervascular axial brain tumours based on preclinical testing and animal studies performed by Arsenal Medical.

The data analysis will consist of descriptive statistics. Participant data listings and tabular and graphical presentations of results will be provided.

Participant demographics, clinical information, and procedural characteristics will be summarised. Continuous variables will be presented as mean, standard deviation, and 95% confidence intervals for the mean. Discrete variables will be presented as frequencies, percentages and exact 95% confidence intervals for discrete variables.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
15/04/2023
Actual
12/04/2023
Date of last participant enrolment
Anticipated
31/10/2023
Actual
13/11/2023
Date of last data collection
Anticipated
1/04/2024
Actual
Sample size
Target
5
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
QLD,WA,VIC
Recruitment hospital [1] 24443 0
Gold Coast University Hospital - Southport
Recruitment hospital [2] 25455 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 40024 0
4215 - Southport
Recruitment postcode(s) [2] 41244 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 311533 0
Commercial sector/Industry
Name [1] 311533 0
Arsenal Medical, Inc.
Country [1] 311533 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Arsenal Medical Australia Pty Ltd,
Address
4 Forest Street, Collingwood, VIC 3066, Australia.
Country
Australia
Secondary sponsor category [1] 312944 0
None
Name [1] 312944 0
Address [1] 312944 0
Country [1] 312944 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310989 0
Monash Health HREC
Ethics committee address [1] 310989 0
246 Clayton Road, Clayton, Victoria, 3168.
Ethics committee country [1] 310989 0
Australia
Date submitted for ethics approval [1] 310989 0
08/06/2022
Approval date [1] 310989 0
19/08/2022
Ethics approval number [1] 310989 0
HREC/86085/MonH-2022-329869(v3)

Summary
Brief summary
The EMBO-01 study is a first-in-human study of a new investigational device, the Distal Penetrating Embolic System (DPE), for pre-operative embolisation of a type of brain tumour that is hypervascular (has a lot of blood vessels) and extra-axial (not part of normal brain tissue). The purpose of this study is to assess the safety and feasibility of using DPE in patients with these types of brain tumours, and to assess whether embolisation can reduce blood loss during surgery and make the tumour easier to remove.

Who is it for?
You may be eligible for this study if you are aged between 18 and 80 years (inclusive), have been diagnosed with a hypervascular extra-axial brain tumour, and are planned for pre-operative embolisation and subsequent surgical removal of the tumour within the next 7 days.

Study details
All participants will undergo the embolisation procedure within 7 days of their surgery. Embolisation is a separate procedure in which a material known as an “embolic agent” is injected into the blood vessel(s) to form a plug within the vessels to stop blood flow to the tumour. The procedure will be done by a specialised doctor called a neurointerventional radiologist, and will take approximately 2 hours to complete. An x-ray will be performed before and after the embolisation process to document successful injection of the DPE into the target vessels supplying the tumour and the effects of this on blood supply to the tumour. During the surgical procedure to remove the tumour, data will also be collected such as blood loss, surgical time, and time taken to remove the tumour. The removed tumour may then be analysed by a pathologist. Additionally, participants will be asked to complete a number questionnaires for up to 90 days post-embolisation to assess for any complications of the procedure.

It is hoped that this study may show that pre-operative embolisation using the DPE is safe and feasible in patients with hypervascular extra-axial brain tumours. It is also hoped that the procedure is able to reduce blood loss during surgery and reduce the time taken to remove the tumour, which may lead the way for a larger trial.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119606 0
Dr Lee-Anne Slater
Address 119606 0
Monash Medical Centre
Monash Imaging
246 Clayton Road
Clayton, VIC, 3168
Country 119606 0
Australia
Phone 119606 0
+61 3 9594 7649
Fax 119606 0
Email 119606 0
[email protected]
Contact person for public queries
Name 119607 0
Lee-Anne Slater
Address 119607 0
Monash Medical Centre
Monash Imaging
246 Clayton Road
Clayton, VIC, 3168
Country 119607 0
Australia
Phone 119607 0
+61 3 9594 7649
Fax 119607 0
Email 119607 0
[email protected]
Contact person for scientific queries
Name 119608 0
Lee-Anne Slater
Address 119608 0
Monash Medical Centre
Monash Imaging
246 Clayton Road
Clayton, VIC, 3168
Country 119608 0
Australia
Phone 119608 0
+61 3 9594 7649
Fax 119608 0
Email 119608 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
10-patient first in human feasibility trial


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.