Spinal MetastasesVERTICALNCT02364115
Randomized Trial Comparing Conventional Radiotherapy With Stereotactic Radiotherapy in Patients With Bone Metastases - VERTICAL Study
A study testing Stereotactic Body Radiotherapy in people with Spinal Metastases and Bone Metastases, run by UMC Utrecht at 1 site in Netherlands.
Trial summary
The purpose of the study is to investigate effectiveness of stereotactic body radiotherapy in patients with bone metastatic disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Spinal Metastases, Bone Metastases
- What is being tested?
- Stereotactic Body Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2015to Aug 2019
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Radiographic evidence of bone metastases
- For spinal lesions; per lesion no more than 3 consecutive spine segments involved with one unaffected vertebral body above and below
- No more than 2 painful lesions needing treatment
- Histologic proof of malignancy
- No compression of spinal cord
- No or mild neurological signs (i.e. radiculopathy, dermatomal sensory change, and muscle strength of involved extremity is Medical Research Council (MRC) 4/5
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- Medically inoperable or patient refused surgery
- Karnofsky performance score (KPS) > 50
- Numeric rating scale (NRS) > 3
- Age > 18 years
- Written informed consent
- Filling out PRESENT-questionnaires
Who cannot join
- Lesion in C1 or C2
- Radio-sensitive histology such as multiple myeloma, lymphoma, small cell, germ cell
- Spinal MRI cannot be completed for any reason (in according with the MRI protocol of the Department of Radiology)
- Impossible to delineate metastasis and organs at risk (OAR) due to artifacts on CT or MRI from previous surgical stabilization
- Unable to undergo SBRT treatment, according to treating doctor's opinion
- Epidural disease
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- Severe, worsening or progressive neurological deficit
- Unstable lesion requiring surgical stabilization
- Patient with < 3 months life expectancy
- Previous EBRT or SBRT to same level
- Chemotherapy or systemic radionuclide delivery within 24 hours before and after SBRT
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Controlled Trial Comparing Conventional Radiotherapy With Stereotactic Body Radiotherapy in Patients With Bone Metastases - VERTICAL Study
The purpose of the study is to investigate effectiveness of stereotactic body radiotherapy in patients with bone metastatic disease.
Read the detailed description
Rationale: Bone metastases are a frequent distant manifestation of solid tumours, and many bone metastases are located in the spine. These patients mostly present with severe (back) pain which reduces quality of life. The primary treatment for pain management is a single-fraction low dose external beam radiation therapy (EBRT), effective in achieving pain reduction in around 60% of patients, of whom 0-23% experience complete pain response. Recently, there is growing evidence that Stereotactic Body Radiotherapy (SBRT) achieves a much higher pain response due to the higher dose administered. In retrospective and a few prospective case series, SBRT for spinal, and also non-spinal metastases has been demonstrated to be safe, and efficacious. However, no randomized controlled trials have been performed.
Objective: To study whether the pain response after three months in patients with osseous metastatic disease increases after SBRT in comparison to low dose EBRT.
Study design: Randomized controlled trial, the VERTICAL study, nested within the PRESENT cohort.
Study population: Eligible patients are MRI-compatible patients with radiographic evidence of bone metastases at the radiotherapy department. Fifty-five patients are recruited in both control and intervention arm.
Intervention: Patients will undergo MRI-based, cone beam CT-guided SBRT and will receive a single dose of 18 Gray (Gy) on the visible metastasis, and 8 Gy on the bony compartment containing the metastasis (e.g. the affected vertebra or pedicle).
Main study parameters/endpoints: The primary endpoint is pain control at three months after radiotherapy. Secondary outcomes are, among others, the occurrence of vertebral compression fracture (VCF) and radiation-induced myelopathy, local tumour control and evaluation of quality of life.
- Conditions
- Spinal Metastases, Bone Metastases
- Being tested
- Stereotactic Body Radiotherapy
- Keywords
- Spinal metastases, Spinal metastatic disease, Stereotactic Body Radiotherapy, Response, Bone metastases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Body RadiotherapyRadiation
Also called Stereotactic Radiosurgery
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic Body Radiotherapy | Experimental | MRI-based, cone beam CT-guided SBRT delivery of a single dose of 18 Gray (Gy) on the visible metastasis, and 8 Gy on the bony compartment containing the metastasis (e.g. the affected vertebra or pedicle). Receives: Radiation: Stereotactic Body Radiotherapy |
| Conventional Radiotherapy | No intervention | Delivery of a single fraction of 8 Gy using virtual simulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete or partial pain response after radiation, defined according to the International Bone Metastases Consensus Endpoints for Clinical Trials.
The primary endpoint of this study is complete or partial pain response after SBRT or EBRT after three months. Complete and partial response, but also possible pain progression or indeterminate response, will be defined according to the International Bone Metastases Consensus Endpoints for Clinical Trials.
Measured: 3 months
Secondary outcomes (7)
Health-Related Quality of Life
Self reported quality of life as measured by the Brief Pain Inventory, European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C15-PAL, and EORTC QLQ BM22
Measured: at 2, 4, 6, 8 weeks, 3 and 6 months, then every 6 months
Progression free survival
Progression free survival is defined as time between treatment and first sign of progression of disease
Measured: up to 3 years
Overall survival
Overall survival is defined as time between treatment and death from any cause
Measured: up to 3 years
Occurrence or progression of vertebral compression fracture (VCF)
VCF is defined as new endplate fracture or collapse deformity as compared with before SBRT or EBRT
Measured: up to 12 months
Occurrence of radiation-induced myelopathy
Radiation-induced myelopathy is defined as a diagnosis of exclusion and defined as neurological signs and symptoms consistent with radiation damage in the form of necrosis to the segment of the spinal cord irradiated, without MRI evidence of recurrent or progressive tumour affecting the spinal cord.
Measured: up to 12 months
Duration of pain relief
Duration of pain relief as measured by the Brief Pain Inventory
Measured: at 2, 4, 6, 8 weeks, 3 and 6 months
Determination of rapidity of pain relief
Rapidity of pain relief as measured by the Brief Pain Inventory
Measured: at 2, 4, 6, 8 weeks, 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionMay 2019
- Study completionAug 2019
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 Spinal MetastasesStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe 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
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Helena M Verkooijen, UMC Utrecht
- Investigators
- Helena M. Verkooijen, MD, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02364115
- Sponsor's protocol ID
- NL49316.041.14
- Acronym
- VERTICAL
- Status last verified
- Feb 2024
- First submitted
- 1 Feb 2015
- Last updated
- 6 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pielkenrood BJ, van der Velden JM, van der Linden YM, Bartels MMT, Kasperts N, Verhoeff JJC, Eppinga WSC, Gal R, Verlaan JJ, Verkooijen HML. Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases-A Phase 2 Randomized Controlled Trial Within a Prospective Cohort. Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):358-367. doi: 10.1016/j.ijrobp.2020.11.060. Epub 2020 Dec 14.
PubMed 33333200van der Velden JM, Verkooijen HM, Seravalli E, Hes J, Gerlich AS, Kasperts N, Eppinga WS, Verlaan JJ, van Vulpen M. Comparing conVEntional RadioTherapy with stereotactIC body radiotherapy in patients with spinAL metastases: study protocol for an randomized controlled trial following the cohort multiple randomized controlled trial design. BMC Cancer. 2016 Nov 21;16(1):909. doi: 10.1186/s12885-016-2947-0.
PubMed 27871280
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial Comparing Conventional Radiotherapy With Stereotactic Body Radiotherapy in Patients With Bone Metastases - VERTICAL Study
- ClinicalTrials.gov ID
- NCT02364115
- Acronym / sponsor ID
- VERTICAL / NL49316.041.14
- Conditions
- Spinal Metastases, Bone Metastases
- Keywords
- Spinal metastases, Spinal metastatic disease, Stereotactic Body Radiotherapy, Response, Bone metastases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- Jan 2015 (actual)
- Primary completion
- May 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 16 Feb 2015 (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 the study is to investigate effectiveness of stereotactic body radiotherapy in patients with bone metastatic disease.
Detailed description
Rationale: Bone metastases are a frequent distant manifestation of solid tumours, and many bone metastases are located in the spine. These patients mostly present with severe (back) pain which reduces quality of life. The primary treatment for pain management is a single-fraction low dose external beam radiation therapy (EBRT), effective in achieving pain reduction in around 60% of patients, of whom 0-23% experience complete pain response. Recently, there is growing evidence that Stereotactic Body Radiotherapy (SBRT) achieves a much higher pain response due to the higher dose administered. In retrospective and a few prospective case series, SBRT for spinal, and also non-spinal metastases has been demonstrated to be safe, and efficacious. However, no randomized controlled trials have been performed.
Objective: To study whether the pain response after three months in patients with osseous metastatic disease increases after SBRT in comparison to low dose EBRT.
Study design: Randomized controlled trial, the VERTICAL study, nested within the PRESENT cohort.
Study population: Eligible patients are MRI-compatible patients with radiographic evidence of bone metastases at the radiotherapy department. Fifty-five patients are recruited in both control and intervention arm.
Intervention: Patients will undergo MRI-based, cone beam CT-guided SBRT and will receive a single dose of 18 Gray (Gy) on the visible metastasis, and 8 Gy on the bony compartment containing the metastasis (e.g. the affected vertebra or pedicle).
Main study parameters/endpoints: The primary endpoint is pain control at three months after radiotherapy. Secondary outcomes are, among others, the occurrence of vertebral compression fracture (VCF) and radiation-induced myelopathy, local tumour control and evaluation of quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stereotactic Body Radiotherapy | Experimental | Radiation: Stereotactic Body RadiotherapyMRI-based, cone beam CT-guided SBRT delivery of a single dose of 18 Gray (Gy) on the visible metastasis, and 8 Gy on the bony compartment containing the metastasis (e.g. the affected vertebra or pedicle). |
| Conventional Radiotherapy | No intervention | –Delivery of a single fraction of 8 Gy using virtual simulation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Radiographic evidence of bone metastases
- For spinal lesions; per lesion no more than 3 consecutive spine segments involved with one unaffected vertebral body above and below
- No more than 2 painful lesions needing treatment
- Histologic proof of malignancy
- No compression of spinal cord
Key exclusion criteria (11 listed)
- Lesion in C1 or C2
- Radio-sensitive histology such as multiple myeloma, lymphoma, small cell, germ cell
- Spinal MRI cannot be completed for any reason (in according with the MRI protocol of the Department of Radiology)
- Impossible to delineate metastasis and organs at risk (OAR) due to artifacts on CT or MRI from previous surgical stabilization
- Unable to undergo SBRT treatment, according to treating doctor's opinion
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 |
|---|---|---|
| Stereotactic Body RadiotherapyAlso: Stereotactic Radiosurgery | Radiation | Stereotactic Body Radiotherapy |
Primary outcome
Complete or partial pain response after radiation, defined according to the International Bone Metastases Consensus Endpoints for Clinical Trials.
Time frame: 3 months
The primary endpoint of this study is complete or partial pain response after SBRT or EBRT after three months. Complete and partial response, but also possible pain progression or indeterminate response, will be defined according to the International Bone Metastases Consensus Endpoints for Clinical Trials.
7 secondary outcomes
Health-Related Quality of Life
Time frame: at 2, 4, 6, 8 weeks, 3 and 6 months, then every 6 months
Progression free survival
Time frame: up to 3 years
Overall survival
Time frame: up to 3 years
Occurrence or progression of vertebral compression fracture (VCF)
Time frame: up to 12 months
Occurrence of radiation-induced myelopathy
Time frame: up to 12 months
Duration of pain relief
Time frame: at 2, 4, 6, 8 weeks, 3 and 6 months
Determination of rapidity of pain relief
Time frame: at 2, 4, 6, 8 weeks, 3 and 6 months
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 6 Feb 2024.
- Derived from this study: PubMed 33333200Pielkenrood BJ, van der Velden JM, van der Linden YM, Bartels MMT, Kasperts N, Verhoeff JJC, Eppinga WSC, Gal R, Verlaan JJ, Verkooijen HML. Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases-A Phase 2 Randomized Controlled Trial Within a Prospective Cohort. Int J Radiat Oncol Biol Phys. 2021 Jun 1;110(2):358-367. doi: 10.1016/j.ijrobp.2020.11.060. Epub 2020 Dec 14.
- Derived from this study: PubMed 27871280van der Velden JM, Verkooijen HM, Seravalli E, Hes J, Gerlich AS, Kasperts N, Eppinga WS, Verlaan JJ, van Vulpen M. Comparing conVEntional RadioTherapy with stereotactIC body radiotherapy in patients with spinAL metastases: study protocol for an randomized controlled trial following the cohort multiple randomized controlled trial design. BMC Cancer. 2016 Nov 21;16(1):909. doi: 10.1186/s12885-016-2947-0.
- Related InfoLink provided by the sponsor.
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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.
Helena M. Verkooijen, MD, PhD principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Body Radiotherapy in people with Spinal Metastases and Bone Metastases, run by UMC Utrecht at 1 site in Netherlands.
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 12 inclusion and 11 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 6 Feb 2024. 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 Netherlands. 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?
Complete or partial pain response after radiation, defined according to the International Bone Metastases Consensus Endpoints for Clinical Trials. (time frame: 3 months). 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 NCT02364115, 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 6 Feb 2024.