Vestibular SchwannomaV-REXNCT02249572
Vestibular Schwannoma - Radiosurgery or Expectation: V-REX.
A study testing gamma knife radiosurgery in people with Vestibular Schwannoma, run by Haukeland University Hospital at 1 site in Norway.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Vestibular Schwannoma
- What is being tested?
- gamma knife radiosurgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteNorway
- Study dates
- 1 Oct 2014to 1 Oct 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Vestibular schwannoma diagnosed by MRI of less than 6 months.
- Diameter 4-20mm. Willing to participate. Age 18 -70 years.
Who cannot join
- Dementia
- Active malignant disease
- Type II neurofibromatosis in patient or first grade relative.
- Other severe co-morbidity
- Type 2 neurofibromatosis in patient or first-grade relative
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Vestibular Schwannoma - Radiosurgery or Expectation
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.
Read more
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.
Read the detailed 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.
- Conditions
- Vestibular Schwannoma
- Being tested
- gamma knife radiosurgery
- Keywords
- Vestibular schwannoma, Radiosurgery, Neurosurgery, Randomized
- Medical subject headings
- Neuroma, Acoustic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gamma knife radiosurgeryRadiation
Leksell Perfection model gamma knife.
| Study group | Role | What they receive |
|---|---|---|
| gamma knife radiosurgery | Experimental | Single fraction gamma knife radiosurgery given at 12 Gy to tumor periphery for vestibular schwannoma Receives: Radiation: gamma knife radiosurgery |
| Expectation | No intervention | No active treatment given for vestibular schwannoma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative Tumor volume
Growth measured as volume ratio V4years/Vbaseline and 1/volume doubling time
Measured: 4 years
Secondary outcomes (3)
Hearing acuity
Hearing acuity according to Gardner Robertson scale at four years
Measured: 4 years
Conversion to other treatment during study period
If patient is in need of other treatment for tumor (radiosurgery, microsurgery, other) within the time frame of the study
Measured: 4 years
Subjective complaints
Penn Vestibular Schwannoma QOL Scale (PANQOL) EQ-50 Scale
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2014 (estimated)
- Study start1 Oct 2014
- Primary completion1 Oct 2017
- Study completion1 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Vestibular SchwannomaStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Block randomization of 100 individuals to radiosurgery or expectative treatment of vestibular schwannoma.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Morten Lund-Johansen, MD PhD, Principal investigator, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02249572
- Sponsor's protocol ID
- 2014/314
- Acronym
- V-REX
- Status last verified
- Mar 2025
- First submitted
- 23 Sep 2014
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dhayalan D, Tveiten OV, Finnkirk M, Storstein A, Hufthammer KO, Goplen FK, Lund-Johansen M; V-REX Trial investigators. Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial. JAMA. 2023 Aug 1;330(5):421-431. doi: 10.1001/jama.2023.12222.
PubMed 37526718Dhayalan D, Tveiten OV, Goplen FK, Finnkirk MK, Storstein AM, Gruner ER, Lund-Johansen M. Comparing the impact of upfront radiosurgery versus expectation in vestibular schwannoma (the V-REX study): protocol for a randomised, observer-blinded, 4-year, parallel-group, single-centre, superiority study. BMJ Open. 2021 Mar 17;11(3):e039396. doi: 10.1136/bmjopen-2020-039396.
PubMed 33737417
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vestibular Schwannoma - Radiosurgery or Expectation
- ClinicalTrials.gov ID
- NCT02249572
- Acronym / sponsor ID
- V-REX / 2014/314
- Conditions
- Vestibular Schwannoma
- Keywords
- Vestibular schwannoma, Radiosurgery, Neurosurgery, Randomized
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- 1 Oct 2014 (actual)
- Primary completion
- 1 Oct 2017 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 25 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Block randomization of 100 individuals to radiosurgery or expectative treatment of vestibular schwannoma.
| Arm | Type | Receives |
|---|---|---|
| gamma knife radiosurgery | Experimental | Radiation: gamma knife radiosurgerySingle fraction gamma knife radiosurgery given at 12 Gy to tumor periphery for vestibular schwannoma |
| Expectation | No intervention | –No active treatment given for vestibular schwannoma |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Vestibular schwannoma diagnosed by MRI of less than 6 months.
- Diameter 4-20mm. Willing to participate. Age 18 -70 years.
Key exclusion criteria (5 listed)
- Dementia
- Active malignant disease
- Type II neurofibromatosis in patient or first grade relative.
- Other severe co-morbidity
- Type 2 neurofibromatosis in patient or first-grade relative
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gamma knife radiosurgeryLeksell Perfection model gamma knife. | Radiation | gamma knife radiosurgery |
Primary outcome
Relative Tumor volume
Time frame: 4 years
Growth measured as volume ratio V4years/Vbaseline and 1/volume doubling time
3 secondary outcomes
Hearing acuity
Time frame: 4 years
Conversion to other treatment during study period
Time frame: 4 years
Subjective complaints
Time frame: 4 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Results publication: PubMed 37526718Dhayalan D, Tveiten OV, Finnkirk M, Storstein A, Hufthammer KO, Goplen FK, Lund-Johansen M; V-REX Trial investigators. Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial. JAMA. 2023 Aug 1;330(5):421-431. doi: 10.1001/jama.2023.12222.
- Derived from this study: PubMed 33737417Dhayalan D, Tveiten OV, Goplen FK, Finnkirk MK, Storstein AM, Gruner ER, Lund-Johansen M. Comparing the impact of upfront radiosurgery versus expectation in vestibular schwannoma (the V-REX study): protocol for a randomised, observer-blinded, 4-year, parallel-group, single-centre, superiority study. BMJ Open. 2021 Mar 17;11(3):e039396. doi: 10.1136/bmjopen-2020-039396.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morten Lund-Johansen, MD PhD principal investigator
Haukeland University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing gamma knife radiosurgery in people with Vestibular Schwannoma, run by Haukeland University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative Tumor volume (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02249572, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2025.