Neurofibromatosis 2
Conditions
Keywords
neurofibromatosis 2, NF2-related schwannomatosis, vestibular schwannoma, bevacizumab, 89Zr-Bevacizumab, PET/CT imaging, hearing
Brief summary
Bevacizumab can be an effective treatment for individuals with NF2 and improve different nerve functions (like hearing, tinnitus or balance problems) and the quality of life of NF2 patients. However, bevacizumab is not effective in all patients or all tumors, at the cost of moderate toxicity and considerable financial burden. Therefore, this observational study will validate an imaging biomarker method to predict bevacizumab efficacy in order to avoid adverse effects and high costs in non-responders to bevacizumab treatment. Patients will undergo standard-of-care treatment with the sole addition of a pre-treatment 89Zr-Bevacizumab PET/CT-scan. Per standard-of-care bevacizumab therapy is administered every three weeks for six months. To monitor treatment effect, follow-up is performed at 3-month intervals.
Interventions
DRUGBevacizumab Zirconium Zr-89
See Arm description.
Sponsors
Leiden University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged 18 years or older * Confirmed diagnosis of NF2 by revised Manchester criteria * Provided written informed consent * Patients must have measurable disease, defined as at least one VS \> 0.4 ml (on volumetric analysis) that can be accurately measured by contrast-enhanced T1-weighted cranial MRI scan. * Eligible and planned for bevacizumab treatment
Exclusion criteria
* Patients with a contra-indication for PET and MRI, such as pregnancy and metal elements. * Patients with a known allergy to substances used in this study * Concurrent treatment with Everolimus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic response (RR) - Diffusion restriction | Baseline | Diffusion restriction, yes / no |
| Hearing response (HR) - PTA | Baseline | Pure Tone Average (PTA), in dB |
| Radiographic response (RR) - tumor volumetry on MRI | Baseline | Size change in volumetric MRI (REiNS criteria); volumetry in mL or mm |
| Radiographic response (RR) - ADC | Baseline | Apparent diffusion coefficient (ADC) of tumor of interest, in mm2/s, on greatest diameter |
| Radiographic response (RR) - Microbleeds | Baseline | Location and number of microbleeds |
| Hearing response (HR) - WRS | Baseline | Word Recognition Score (WRS), % at x dB |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient reported outcome measures (PROM) | Baseline | Questionnaire on Quality of Life, and presence of symptoms |
| Physical examination | Baseline | General neurological examination is performed to assess if the patient has neurological symptoms, if any. The examination is done according to standard clinical care and has a descriptive nature. Cranial nerve (dys)function, including House Brackmann scale for the facial nerve (n. VII) and trigeminal nerve function (n. V), including presence of neuralgia and hypoesthesia, are described in more detail. |
| Renal function | Baseline | Creatinine clearance (CrCl), eGFR (mL/minute, ref. \>90) |
| Vestibular Function | Baseline | Video-Head Impulse Test (vHIT) |
Countries
Netherlands
Contacts
Primary ContactJules PJ Douwes, MD
Backup ContactErik F Hensen, MD, PhD
Outcome results
None listed