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Trial registered on ANZCTR


Registration number
ACTRN12622000218796p
Ethics application status
Not yet submitted
Date submitted
10/01/2022
Date registered
7/02/2022
Date last updated
7/02/2022
Date data sharing statement initially provided
7/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
An interventional trial comparing ferumoxytol and gadolinium for estimating the immune cell content in brain tumours.
Scientific title
A Main Study to Determine the Diagnostic Utility of the ultrasmall superparamagnetic iron oxide (USPIO) MRI Scan in Tracking Macrophages in Patients with Glioblastoma and brain tumour metastases
Secondary ID [1] 306152 0
Nil Known
Universal Trial Number (UTN)
U1111-1273-1300
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stage 3 and 4 astrocytoma 324855 0
brain tumour metastasis 324856 0
Condition category
Condition code
Cancer 322290 322290 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a main, prospective, interventional study performing specific MRI brain sequence pre and post intravenous administration of an iron oxide compound (ferumoxytol) used here off label as an MRI contrast agent in 40 patients with a preliminary radiological diagnosis of primary stage 3 or 4 astrocytoma, and 40 patients with a preliminary radiological diagnosis of a secondary tumour (brain metastasis from the colon, breast, lung and melanoma). Following preliminary diagnosis of primary stage 3 or 4 astrocytoma, or a secondary tumour using gadolinium contrast MRI, an intravenous infusion of ferumoxytol (2.6 mg/kg diluted in 100 ml of normal saline and infused over a 30 minutes period) will be administered by a radiologist, radiology registrar, or surgical registrar, followed by MRI scanning 24 hours later. The MRI scan will take approximately 40 minutes to complete. Ferumoxytol MRI will occur between 12 hours and 5 days following the gadolinium MRI. The fermumoxytol infusion will be supervised, and the MRI sequences checked for the superparamagnetic properties of iron. As part of the participants standard of care the tumour will be removed and the tumour tissue excised will be measured for iron using special staining to monitor adherence to the intervention.
Intervention code [1] 322560 0
Diagnosis / Prognosis
Comparator / control treatment
Participants will act as their own control, and will receive both the intervention (ferumoxytol) and the control (gadolinium) MR imaging sequences. Each patient acts as their own control standard: brain tumour images following gadolinium MRI are compared to those following ferumoxytol infusion and MRI. The gadolinium contrast MRI will occur 1-5 days prior to the ferumoxytol-MRI. Gadolinium will be administered by a radiologist or radiology registrar. The gadolinium MRI is approximately 40 minutes. Gadolinium (0.1mmol/kg (standard)-0.2 mmol/kg (maximum)) will be administered by intravenous infusion and the MRI started within 10 minutes after gadolinium administration. The MRI image is examined within 24 hours (T1 weighted) to check that the gadolinium was administered.
Control group
Active

Outcomes
Primary outcome [1] 330052 0
Diagnostic accuracy of ferumoxtyol contrast MRI will be assessed, using gadolinium contrast MRI as the gold standard. MRI brain tumour imaging comparison between gadolinium and ferumoxytol contrast agents. MRI sequences T1, T2, Flair, susceptibility weighted sequence (SWI) and post contrast T1 will be assessed for each participant. Each case was read in the Public Hospital Patient Archive Communication System (PACS). All scans were reviewed by at least two radiologists.
All images will be compared as a composite primary outcome.
Timepoint [1] 330052 0
Within 12 months of the ferumoxytol contrast MRI
Primary outcome [2] 330053 0
Correlation of MRI brain tumour imaging features using ferumoxytol contrast and tumour macrophage content determined using histology. Ferumoxtyol MRI sequences T1, T2, Flair, susceptibility weighted sequence (SWI) and post contrast T1 will be assessed for each participant to find cases with additional regions of enhancement compared to the gadolinium MRI sequences. Tumour associated macrophage content will be measured using Cd163 immunohistochemistry staining on excised tumour tissue and the percentage of Cd163 cells counted. Tumours will be excised as part of standard of care to remove the tumour. All MR mages will be compared as a composite primary outcome.
Timepoint [2] 330053 0
Within 12 months following MRI
Secondary outcome [1] 404739 0
Patient survival will be assessed by accessing the patient electronic medical records. This will be done by the neurosurgeron or the radiologists involved in the study .
Timepoint [1] 404739 0
Participant survival at 6 months, 12 months, and 24 months post enrolment will be obtained.

Eligibility
Key inclusion criteria
1. Patients with an imaging diagnosis based on the baseline diagnostic MRI scan (gadolinium contrast) of primary stage 3 or 4 astrocytoma, or brain tumour metastasis.
2. No steroid treatment that has been administered to the patients between the time of the baseline diagnostic scan and the ferumoxytol infusion.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who are younger than 18 years old.
2. Patients who are pregnant or breast feeding.
3. Patients who have known allergy to iron preparations or other medication allergies.
4. Patients who have haemochromatosis or known clinically significant liver function abnormalities.
5. The initial diagnostic MRI demonstrates intracranial haemorrhage, calcification or other susceptibility blooming artifacts.

Study design
Purpose of the study
Diagnosis
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
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on a power calculation (alpha 0.05, Beta 0.2 to give Power at 0.8) assuming ferumoxytol MRI will predict a high macrophage content in 80% of cases we require at least ten patients with a high macrophage content in their tumours to show that the macrophage content can be determined using ferumoxytol. In previous work by the group one third of patients had tumours with a high content of macrophages so at least 30 individuals with a grade 3 and 4 astrocytoma and 30 individuals with a brain tumour metastasis would be required. This study aims to recruit 80 individuals.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2022
Actual
Date of last participant enrolment
Anticipated
1/04/2025
Actual
Date of last data collection
Anticipated
1/04/2027
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment outside Australia
Country [1] 24482 0
New Zealand
State/province [1] 24482 0

Funding & Sponsors
Funding source category [1] 310493 0
University
Name [1] 310493 0
University of Otago
Country [1] 310493 0
New Zealand
Primary sponsor type
Individual
Name
Tania Slatter
Address
Department of Pathology
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
New Zealand
Country
New Zealand
Secondary sponsor category [1] 311659 0
Individual
Name [1] 311659 0
Ahmad Taha
Address [1] 311659 0
Department of Neurosurgery
Southern District Health Board
201 Great King Street, Dunedin Central, Dunedin 9016
New Zealand
Country [1] 311659 0
New Zealand
Secondary sponsor category [2] 311664 0
Individual
Name [2] 311664 0
Noelyn Hung
Address [2] 311664 0
Department of Pathology, Dunedin School of Medicine, University of Otago, PO Box 56 Dunedin 9054, New Zealand
Country [2] 311664 0
New Zealand
Other collaborator category [1] 282119 0
Individual
Name [1] 282119 0
Jean Zhou
Address [1] 282119 0
Department of Radiology
Dunedin Hospital Southern District Health Board
201 Great King St
Dunedin 9016
New Zealand
Country [1] 282119 0
New Zealand

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 310123 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 310123 0
Ethics committee country [1] 310123 0
New Zealand
Date submitted for ethics approval [1] 310123 0
28/02/2022
Approval date [1] 310123 0
Ethics approval number [1] 310123 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116554 0
Dr Ahmad Taha
Address 116554 0
Department of Neurosurgery
Dunedin Hospital Southern District Health Board
201 Great King Street, Dunedin Central, Dunedin 9016
Country 116554 0
New Zealand
Phone 116554 0
+64 27 254 1243
Fax 116554 0
Email 116554 0
ahmad.taha@southerndhb.govt.nz
Contact person for public queries
Name 116555 0
Tania Slatter
Address 116555 0
Department of Pathology
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9016
Country 116555 0
New Zealand
Phone 116555 0
+64 211104733
Fax 116555 0
Email 116555 0
tania.slatter@otago.ac.nz
Contact person for scientific queries
Name 116556 0
Tania Slatter
Address 116556 0
Department of Pathology
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9016
Country 116556 0
New Zealand
Phone 116556 0
+64 211104733
Fax 116556 0
Email 116556 0
tania.slatter@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified individual data collected as part of the trial will be available once the study findings are published online.
When will data be available (start and end dates)?
The case will be immediately available once it is published online with no end date determined.
Available to whom?
Anyone who wishes to access this.
Available for what types of analyses?
Any purpose for published data.
How or where can data be obtained?
Unrestricted access via the publications website or pubmed (the publication will be open access)


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14624Ethical approval  tania.slatter@otago.ac.nz
14625Study protocol  tania.slatter@otago.ac.nz



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.