E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this feasibility study is to validate pre-treatment 89Zr-Bevacizumab PET/CT as an imaging biomarker for prediction of a hearing response to bevacizumab treatment in patients with NF2 related (vestibular) schwannomas. All patients will undergo standard-of-care treatment with an additional baseline 89Zr-Bevacizumab PET/CT. PET/CT imaging will be performed 4 days after intravenous infusion of 89Zr-Bevacizumab.
The primary endpoint will be the correlation of the results of the pre-treatment 89Zr-Bevacizumab with the proportion of patients with confirmed hearing response (HR) and radiographic response (RR) to bevacizumab therapy. |
|
E.2.2 | Secondary objectives of the trial |
Secondary end points are correlations of pre-treatment 89Zr-Bevacizumab PET/CT imaging with patient-reported outcome measures (PROM), cranial nerve (dys)function, kidney function and nontarget schwannoma response after bevacizumab treatment in NF2-patients. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Patients aged 18 years or older
- Confirmed diagnosis of NF2 by revised Manchester criteria (appendix C)
- 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 |
|
E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- 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
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
All stated study parameters will be assessed for a correlation to the pre-treatment 89Zr-bevacizumab PET/CT, in order to determine its predictive ability for bevacizumab treatment effect.
- Hearing Response (HR)
- Word Recognition Score (WRS)
- Pure Tone Average (PTA) / High Fletcher Index (HFI)
- Radiographic Response (RR)
- Size change in volumetric MRI (REiNS criteria [24])
- Changes in ADC values, microbleeds and perfusion |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 89Zr-bevacizumab PET/CT imaging en concomitant 6 month standard-of-care bevacizumab treatment |
|
E.5.2 | Secondary end point(s) |
- Durability of HR
- Patient reported outcome measures (PROM)
- Dizziness
- Tinnitus
- Quality of Life (QoL)
- Facial nerve function: House Brackman scale (HB)
- Facial spasms: yes / no, and need for Botox
- Trigeminal nerve function
- General neurological function
- Peripheral schwannomas: size measurement and - when applicable - impairment level
- Renal function |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 89Zr-bevacizumab PET/CT imaging en concomitant 6 month standard-of-care bevacizumab treatment |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |