Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02249572 |
| Other study ID # |
2014/314 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2014 |
| Est. completion date |
October 1, 2021 |
Study information
| Verified date |
October 2021 |
| Source |
Haukeland University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to compare the outcome of patients with vestibular schwannomas
in two groups of randomised to either radiosurgery or expectation.
The optimal treatment for a small vestibular schwannoma is a matter of controversy and there
are no class 1 studies investigating this. Even the natural tumor growth rate remains
controversial and is reported to be from near 100% of cases showing growth to 40-60% in
various reports. The clinical results of various treatment strategies are documented, but
comparative studies are very few. Immediate radiosurgery or wait-and scan with subsequent
treatment upon growth are two strategies that have both been used in many different centers.
There are only two studies comparing these treatment modalities .These studies indicate
significant effect of GKRS in reducing tumor growth, with less differences in hearing and
complaint outcomes. None of the studies are blinded or randomised, allowing for bias.
The present study aims at comparing the two modalities above. To achieve this, we intend to
randomise patients with newly diagnosed VS to either of Wait-and Scan or immediate
radiosurgery.
The primary study endpoint is the relative tumor size measured as the ratio between tumor
volume at four years compared with volume at inclusion. Secondary endpoints include symptom
and sign development measured by clinical examination and by patient's responses to
standardised validated questionnaires. In addition, the health economics involved with both
strategies will be evaluated and compared, as well as the patient's working status.
Patients will be asked to participate if their VS is diagnosed within the last six months,
their age is between 18 and 70, and pending there are no exclusion criteria (see below). A
power analysis indicates that about 50 patients per group is sufficient.
In case of failure to recruit patients, we will change the design to a study based on
patient's own choice of treatment.
The study will be announced according to international guidelines. A steering committee will
monitor the study and an intermediate analysis will be performed when the study group has
been followed for two years. If the effect aim is already observed, the study should
nonetheless continue, as it is too early to evaluate the results after such a short time
course.
It will also be discussed to do a follow-up of all patients ten years after inclusion.
Description:
Study design and purpose:
Design: Randomised study blinded to observer on primary endpoint (tumor volume).
Intention-to-treat, ie patients who cross over from conservative to GKRS group during the
study period are assigned to their original group. Patients who refrain from radiosurgery
despite randomisation are assigned to radiosurgery group.
Purpose: compare the treatment of small and medium-sized VS treated with a standardised dose
of 12 Gy to the tumor periphery with expectative treatment.
Primary endpoint:
Growth measured as volume ratio V4years/Vbaseline and 1/volume doubling time, evaluated by T1
contrast MRI volumetry at one, two, three and four years.
Secondary endpoints:
Hearing acuity according to Gardner Robertson scale at four years (safety endpoint).
Conversion to other treatment during study period Adverse effects
Subjective complaints assessed by questionnaires:
Penn Vestibular Schwannoma QOL Scale EQ-50 Scale
Investigations:
Prior to inclusion: MRI less than 6 months showing VS.
After inclusion and at 1,2 3,4 years, all at study site:
MRI of inner ear (acoustic neuroma protocol) Balance platform Nystagmometry Audiometry
Effect registration:
Main variable:
Tumor volume, measured on a T1 contrast MRI scan with 2mm slice interval/thickness. For
study, the measurement is to be done by a blinded observer.
Economy. Costs associated with study are financed by research donations from Helse-Vest and
The National Center for Vestibular Schwannomas.
Radiology: Image based tumor volumes As the primary endpoint is relative tumor size, an
accurate measure of tumor volume and changes thereof, is mandatory. This will be obtained
using a state-of-the-art magnetic resonance imaging (MRI) system suited for acquiring high
resolution (1mm3), three dimensional (3D) anatomical images. A 1.5T imaging system which
meets the required field homogeneity will be used for imaging. The image contrast will be T1
weighted with gadolinium based contrast agent, yet a T2 weighted image volume will also be
included (preferably also acquired in 3D). An identical imaging protocol will be acquired at
each time point (prior to randomization, on site follow up, 4-year annual follow up), and
image slices will be positioned according to anatomical landmarks in each patients to
minimize variability across time. All 3D acquisitions will be performed with sagittal slicing
to minimize artifacts, but will also be reformatted into coronal and axial views (1mm slice
thickness, no gap between slices) on the scanner system.
The subsequent imaging processing, i.e. the estimation of tumor volume and longitudinal
changes thereof, will be performed using available software at time of analysis.
Study schedule
Clinical examination, MRI, Questionnaires, Audiometry, Vestibular tests are done at baseline
and then annually for 4 years. Patients randomised for radiosurgery are treated within 3
months after baseline.
