Vestibular Schwannoma - Radiosurgery or Expectation: V-REX. (V-REX)

• ClinicalTrials.gov Identifier: NCT02249572
• Recruitment Status: Completed
• First Posted: September 25, 2014
• Last Update Posted: October 20, 2022
• Sponsor: Haukeland University Hospital
• Information provided by (Responsible Party): Haukeland University Hospital

Tracking Information

• First Submitted Date: September 23, 2014
• First Posted Date: September 25, 2014
• Last Update Posted Date: October 20, 2022
• Actual Study Start Date: October 1, 2014
• Actual Primary Completion Date: October 1, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 23, 2014)

Relative Tumor volume [ Time Frame: 4 years ]

Growth measured as volume ratio V4years/Vbaseline and 1/volume doubling time

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 23, 2014)

• Hearing acuity [ Time Frame: 4 years ]
  Hearing acuity according to Gardner Robertson scale at four years
• Conversion to other treatment during study period [ Time Frame: 4 years ]
  If patient is in need of other treatment for tumor (radiosurgery, microsurgery, other) within the time frame of the study
• Subjective complaints [ Time Frame: 4 years ]
  Penn Vestibular Schwannoma QOL Scale (PANQOL) EQ-50 Scale

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 23, 2014)

Neurovestibular testing [ Time Frame: 4 years ]

Outcomes of caloric test and Balance Platform test (Equitest, SOT)

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Vestibular Schwannoma - Radiosurgery or Expectation: V-REX.
• Official Title: Vestibular Schwannoma - Radiosurgery or Expectation

Brief 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.

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 Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Block randomization of 100 individuals to radiosurgery or expectative treatment of vestibular schwannoma.

Masking: Double (Investigator, Outcomes Assessor)
Masking Description:

Study investigator masked to whether patient has had radiosurgery og no active treatment. Scars due to radiosurgery frame hidden With surgical cap at all study consultations in all pts. Radiologist measuring tumor size masked as to treatment

Primary Purpose: Treatment

• Condition: Vestibular Schwannoma

Intervention

Radiation: gamma knife radiosurgery

Leksell Perfection model gamma knife.

Study Arms

• Experimental: gamma knife radiosurgery
  Single fraction gamma knife radiosurgery given at 12 Gy to tumor periphery for vestibular schwannoma
  Intervention: Radiation: gamma knife radiosurgery
• No Intervention: Expectation
  No active treatment given for vestibular schwannoma

• Publications *: Dhayalan 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 23, 2014): 100
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 1, 2021
• Actual Primary Completion Date: October 1, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Vestibular schwannoma diagnosed by MRI of less than 6 months.
• Diameter 4-20mm. Willing to participate. Age 18 -70 years.

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT02249572
• Other Study ID Numbers: 2014/314
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Haukeland University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Haukeland University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Morten Lund-Johansen, MD PhD; Haukeland University Hospital

• PRS Account: Haukeland University Hospital
• Verification Date: October 2021