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NCT Number: NCT06572475

USPIO Enhanced MR Imaging in CNS Tumours (UMIC)

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.

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Key information

Conditions

Vestibular Schwannoma Astrocytoma Cranial Nerve Diseases Cranial Nerve Neoplasms Ear Diseases Glioma Glioma, Astrocytic Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Nerve Sheath Neoplasms Nervous System Diseases Nervous System Neoplasms Neurilemmoma Neuroectodermal Tumors Neuroendocrine Tumors Neuroma Neuroma, Acoustic Otorhinolaryngologic Diseases Otorhinolaryngologic Neoplasms Peripheral Nervous System Neoplasms Retrocochlear Diseases Vestibulocochlear Nerve Diseases

Age range

16 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Salford Royal Hospital Northern Care Alliance NHS Foundation Trust

Salford, Greater Manchester, M6 6HD, United Kingdom

Location status: Recruiting

Location contact

Hannah Howlett

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

USPIO enhanced MRI

Diagnostic Test

Ferumoxytol (Feraheme©, AMAG pharmaceuticals, US) enhanced MRI

Primary outcomes

  1. 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.

    Time frame: Three years

    Use correlation tests to establish the relationship between delayed (24-48 hr) USPIO related MRI signal intensity changes and tissue markers of TAM density and microvascular markers.

  2. 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.

    Time frame: Three years

    Differences in the enhancement pattern between post GBCA T1W images and the delayed (24-48hr) ferumoxytol enhanced T1W images will be compared through visual inspection and use of the structural similarity index

  3. 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.

    Time frame: Three years

    Use voxelwise correlation tests and ROI analysis to establish the relationship between microvascular parameters derived from dynamic contrast enhanced (DCE) MRI) and USPIO related signal intensity changes at early (<2hr) and delayed (24-48 hr) imaging timepoints in these tumours.

  4. 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).

    Time frame: Three years

    Evaluate using appropriate parametric and non-parametric statistical tests if there are differences between non-growing and growing VS in USPIO related signal intensity changes on acquired T1, T2 and T2* weighted imaging at early (<2hr) and delayed (24-48 hr) imaging timepoints. Evaluate using correlation and regression analyses if there is a relationship between tumour size and USPIO related signal intensity changes on acquired T1, T2 and T2* weighted imaging at early (<2hr) and delayed (24-48 hr) imaging timepoints.

  5. 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.

    Time frame: Three years

    Immunohistochemistry (IHC)/ immunofluorescence will be used on both formalin fixed paraffin embedded (FFPE) and frozen tissue samples to map the uptake of USPIO within immune and non-immune cell populations.

  6. 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.

    Time frame: Three years

    Evaluate using appropriate parametric and non-parametric statistical tests if there are differences in USPIO related signal intensity changes and immune cell infiltration within regions of histologically proven transformation when compared to non-transformed areas.

Study contacts

Contact information is provided by the study sponsor or research team.

Daniel Lewis, PhD MBBS

CONTACT

[email protected]

+441612067050

Sponsors and collaborators

Lead sponsor

Northern Care Alliance NHS Foundation Trust

Other

Registry information

Official study 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)

Acronym: UMIC

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Aug 27, 2024
Registry last updated
Aug 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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