Clinical trial NCT06572475: USPIO Enhanced MR Imaging in CNS Tumours (UMIC)
Official title: USPIO Enhanced MR Imaging in CNS Tumours (UMIC) : A Pilot Study of Ferumoxytol (Feraheme ©) as an Imaging Biomarker of Tumour Associated Macrophage (TAM) Infiltration in Vestibular Schwannoma (VS) and Transforming Low Grade Glioma (LGG)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Vestibular Schwannoma
Glioma, Astrocytic
Lead sponsor: Northern Care Alliance NHS Foundation Trust
Sponsor class: OTHER
First posted: 2024-08-27
Enrollment: 17
Sex: ALL
Minimum age (years): 16
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The immune response or inflammation is known to be a key driver of progression and growth in many solid tumours. Inflammatory cells called macrophages are present in high numbers in many brain tumours and these tumour associated macrophages or TAM are thought to have prognosis and treatment implications in these tumours. A key question, however, is how this inflammation or TAM abundance can be detected, measured and monitored in the clinic. A clinically applicable imaging test that can directly and accurately measure tumour macrophage content would be of considerable value and one technique that may provide this is USPIO enhanced magnetic resonance imaging (MRI). Following intravenous injection, USPIO or ultrasmall superparamagnetic iron oxide nanoparticles, circulate in the bloodstream before being taken up by inflammatory cells/macrophages in tumour tissue, wherein they can be detected by MRI. This pilot study is to evaluate if a commercially available USPIO preparation called ferumoxytol (Feraheme ©) can accurately quantify macrophage abundance in brain tumours, with an exploratory focus on vestibular schwannoma (VS) and suspected transforming low-grade glioma (LGG). Patients with both non-growing (static) and growing VS, and patients with suspected transforming LGG will undergo dedicated MRI sequences before, immediately after (\< 2 hours) and at both 24 and 48hrs after ferumoxytol administration. In patients undergoing surgery, acquired imaging will be compared with resected tumour tissue so that markers of inflammation can be compared with USPIO uptake. Through advanced laboratory methods this study will seek to establish within resected VS and LGG specimens: the cellular destination/s of USPIO uptake; the nature of the inflammatory and/or tumour cells containing the USPIO; and the relationship between USPIO uptake and tumour blood vessel permeability or leakiness.


Eligibility criteria: Inclusion Criteria:

* Be at least 16 years old
* Have a CNS tumour suspected to be one of the defined histological types (vestibular scwhannoma or low grade glioma)
* Be able to lie still for up to 1 hour comfortably
* Opinion of the treating clinician is that the patient will be able to successfully complete the research imaging protocol.

Exclusion Criteria:

* Life expectancy less than 1 year
* Previous CNS radiotherapy/ stereotactic radiosurgery (SRS)
* Females who are pregnant/ breastfeeding
* Patients with an eGFR \< 30ml/min
* Patients with known and documented history of iron overload/haemosiderosis/ haemochromatosis
* Patients with immune or inflammatory conditions e.g. systemic lupus erythematous, rheumatoid arthritis
* Patients with absolute (e.g. pacemaker) and relative (anxiety or claustrophobia) contraindications to MR scanning
* Patients with a history of allergic reaction to iron or dextran
* Patients with a history of allergic reaction to gadolinium contrast agents, asthma or renal problems
* Patients who are unable to adequately understand verbal explanations or written information given in English.

Primary outcomes:
measure: Establish in a cohort of surgically resected sporadic VS if the enhancement pattern of delayed (24-48 hr) USPIO uptake correlates with tissue markers of TAM density and tissue microvascular markers.
timeFrame: Three years
measure: Establish the relationship between enhancement patterns following GBCA administration and the volume, pattern and intensity of early (<2hr) and delayed (24-48 hr) USPIO imaging in these tumours.
timeFrame: Three years
measure: Evaluate the association between microvascular parameters derived from dynamic contrast enhanced (DCE) MRI) and the volume, pattern and intensity of early (<2hr) and delayed (24-48 hr) USPIO imaging in these tumours.
timeFrame: Three years
measure: Establish in VS the relationship between the volume, pattern and intensity of early (<2hr) and delayed (24-48 hr) USPIO imaging in these tumours with tumour size and tumour growth status (non-growing or static vs growing).
timeFrame: Three years
measure: Establish within resected VS and transforming low-grade glioma specimens the cellular destination/s of USPIO internalisation and the in vivo relationship between BBB disruption and USPIO extravasation.
timeFrame: Three years
measure: Establish if the enhancement pattern of delayed (24-48 hr) USPIO uptake correlates with loco-regional tissue markers of immune cell infiltration and malignant transformation within imaged transforming low grade glioma.
timeFrame: Three years
Secondary outcomes:
Other outcomes:
Locations:
city: Salford
country: United Kingdom
facility: Salford Royal Hospital Northern Care Alliance NHS Foundation Trust
state: Greater Manchester
Study officials:
affiliation: Northern Care Alliance NHS Foundation Trust
name: David Coope, PhD FRCS(SN)
role: PRINCIPAL_INVESTIGATOR
References: