89Zr-Bevacizumab PET/CT Imaging in NF2 Patients

Study Overview
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Brief Summary
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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.

Official Title
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89Zr-Bevacizumab PET/CT Imaging of Vestibular Schwannomas for the Prediction of Bevacizumab Treatment Effect in Patients With Symptomatic Neurofibromatosis Type 2

Conditions
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Neurofibromatosis 2

Intervention / Treatment
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* Drug: Bevacizumab Zirconium Zr-89


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bevacizumab<br>After determining eligibility, all patients will undergo standard-of-care treatment with the sole addition of a pre-treatment 89Zr-Bevacizumab PET/CT-scan. Patients will first receive 5 mg 89Zr-Bevacizumab 4 days before PET/CT scan. This is followed by standard-of-care intravenous 7.5mg/kg bevacizumab (Avastin) therapy, administered every three weeks for six months | Drug: Bevacizumab Zirconium Zr-89<br>* See Arm description.<br>* Other names: Bevacizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hearing response (HR) - WRS | Word Recognition Score (WRS), % at x dB | Baseline | 
| Hearing response (HR) - WRS | Word Recognition Score (WRS), % at x dB | 3 months | 
| Hearing response (HR) - WRS | Word Recognition Score (WRS), % at x dB | 6 months | 
| Hearing response (HR) - PTA | Pure Tone Average (PTA), in dB | Baseline | 
| Hearing response (HR) - PTA | Pure Tone Average (PTA), in dB | 3 months | 
| Hearing response (HR) - PTA | Pure Tone Average (PTA), in dB | 6 months | 
| Radiographic response (RR) - tumor volumetry on MRI | Size change in volumetric MRI (REiNS criteria); volumetry in mL or mm | Baseline | 
| Radiographic response (RR) - tumor volumetry on MRI | Size change in volumetric MRI (REiNS criteria); volumetry in mL or mm | 3 months | 
| Radiographic response (RR) - tumor volumetry on MRI | Size change in volumetric MRI (REiNS criteria); volumetry in mL or mm | 6 months | 
| Radiographic response (RR) - ADC | Apparent diffusion coefficient (ADC) of tumor of interest, in mm2/s, on greatest diameter | Baseline | 
| Radiographic response (RR) - ADC | Apparent diffusion coefficient (ADC) of tumor of interest, in mm2/s, on greatest diameter | 3 months | 
| Radiographic response (RR) - ADC | Apparent diffusion coefficient (ADC) of tumor of interest, in mm2/s, on greatest diameter | 6 months | 
| Radiographic response (RR) - Microbleeds | Location and number of microbleeds | Baseline | 
| Radiographic response (RR) - Microbleeds | Location and number of microbleeds | 3 months | 
| Radiographic response (RR) - Microbleeds | Location and number of microbleeds | 6 months | 
| Radiographic response (RR) - Diffusion restriction | Diffusion restriction, yes / no | Baseline | 
| Radiographic response (RR) - Diffusion restriction | Diffusion restriction, yes / no | 3 months | 
| Radiographic response (RR) - Diffusion restriction | Diffusion restriction, yes / no | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vestibular Function | Video-Head Impulse Test (vHIT) | Baseline | 
| Vestibular Function | Video-Head Impulse Test (vHIT) | 3 months | 
| Vestibular Function | Video-Head Impulse Test (vHIT) | 6 months | 
| Vestibular Function | cervical Vestibular Evoked Myogenic Potential (cVEMP) test | Baseline | 
| Vestibular Function | cervical Vestibular Evoked Myogenic Potential (cVEMP) test | 3 months | 
| Vestibular Function | cervical Vestibular Evoked Myogenic Potential (cVEMP) test | 6 months | 
| Vestibular Function | Caloric test | Baseline | 
| Vestibular Function | Caloric test | 3 months | 
| Vestibular Function | Caloric test | 6 months | 
| Patient reported outcome measures (PROM) | Questionnaire on Quality of Life, and presence of symptoms | Baseline | 
| Patient reported outcome measures (PROM) | Questionnaire on Quality of Life, and presence of symptoms | 3 months | 
| Patient reported outcome measures (PROM) | Questionnaire on Quality of Life, and presence of symptoms | 6 months | 
| Physical examination | 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. | Baseline | 
| Physical examination | 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. | 3 months | 
| Physical examination | 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. | 6 months | 
| Renal function | Creatinine clearance (CrCl), eGFR (mL/minute, ref. >90) | Baseline | 
| Renal function | Creatinine clearance (mmol/L), eGFR (mL/minute) | 3 months | 
| Renal function | Creatinine clearance (mmol/L), eGFR (mL/minute) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurofibromatosis 2, NF2-related schwannomatosis, vestibular schwannoma, bevacizumab, 89Zr-Bevacizumab, PET/CT imaging, hearing