Vestibular schwannoma Cancer
Conditions
Interventions
The focus of this study is to validate a panel of biomarkers of response to IL-1 antagonism in patients with VS. Ten patients who are listed for surgical resection of a growing sporadic or NF2-related
Dotarem, Guerbet S.A.) up to a maximum dose of 0.2 mmol/kg. From this baseline imaging, imaging parameters relevant to VS growth, such as tumoural diffusion metrics and dynamic contrast enhanced (DCE)
Sponsors
University of Manchester
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Adult patient (>=18 years old) diagnosed with a growing VS, for whom surgical resection is planned
Exclusion criteria
Exclusion criteria: 1. Uncertain diagnosis of VS 2. Known active tuberculosis or active hepatitis. 3. Known active malignancy. 4. Known Still’s Disease 5. Neutropenia (ANC <1.5 x 109 /L ) 6. Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) <30 ml/minute) documented in the last 3 months 7. Live vaccinations within the last 10 days (please see Appendix 1) 8. Previous or concurrent treatment with IL-1Ra known at the time of study entry or previous participation in this study 9. Current treatment with TNF antagonists (please see below for the prohibited medication) 10. Known to have participated in a clinical trial of an investigational agent or device in the 30 days prior to study enrolment 11. Known to have participated in a clinical trial of an investigational agent or device within five half-lives (of the previous agent or device) 12. Known to be pregnant or breastfeeding or inability to reliably confirm that the patient is not pregnant (please see further guidance on pregnancy prevention below) 13. Clinically significant serious concurrent medical condition, pre-morbid illnesses, or concurrent serious infection (including confirmed or suspected COVID-19 infection), at the PI’s (or designee’s) discretion, which could affect the safety or tolerability of the intervention. Please see the precaution of use section for further guidance. 14. Known allergy to IL-1Ra or any of the excipients listed in the drug SmPC (please see section below) 15. Known allergy to other products that are produced by DNA technology using the microorganism E. coli (i.e., E. coli-derived protein) 16. Current treatment with IL-6 or IL-1 inhibitors or drugs affecting the IL-1 axis. Please see below for the prohibited medication 17. Current treatment with CYP450 substrates with a narrow therapeutic index (e.g., warfarin and phenytoin) 18. Previous active treatment for VS, including previous surgical resection; previous stereotactic radiosurgery or fractionated radiotherapy; or the administration of bevacizumab within 3 months of study enrolment. 19. Inability to provide informed consent to participate in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative abundance of key inflammatory genes in anakinra-dosed VS (TNF-a, IL-1ß, IL-6, IL-18, NLRP3) compared to a control cohort of size and growth-matched VS, measured using quantitative PCR analyses on tumour tissue specimens obtained at time of surgical resection and after 14 days of anakinra dosing. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Delivery of anakinra across the blood-nerve barrier to VS measured using MALDI-TOF mass spectrometry on tumour tissue specimens obtained at time of surgical resection and after 14 days of anakinra dosing 2. Circulating biomarkers of inflammation (IL1-a, IL1-ß, IL-6, IL-18, IL-33) measured using multiplex cytokine assays from baseline (day 0) to day 12-14 3. VS tumour microenvironment measured using tumour DCE-MRI-derived microvascular parameters (Ktrans, ve, vp, absolute tumour blood flow) from baseline (day 0) to days 12-14 4. VS tumour microenvironment cellular composition measured using absolute and relative inflammatory cell (macrophage, T cell) abundance, measured on tumour tissue specimens obtained at time of surgical resection and after 14 days of anakinra dosing | — |
Countries
England, United Kingdom
Contacts
Public ContactDaniel Lewis
Outcome results
None listed