Clinical trial NCT02364115: Randomized Trial Comparing Conventional Radiotherapy With Stereotactic Radiotherapy in Patients With Bone Metastases - VERTICAL Study
Official title: Randomized Controlled Trial Comparing Conventional Radiotherapy With Stereotactic Body Radiotherapy in Patients With Bone Metastases - VERTICAL Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Metastases
Bone Metastases
Keywords: Spinal metastases
Spinal metastatic disease
Stereotactic Body Radiotherapy
Response
Bone metastases
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2015-02-16
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Complete or partial pain response after radiation, defined according to the International Bone Metastases Consensus Endpoints for Clinical Trials.
timeFrame: 3 months
Secondary outcomes:
measure: Health-Related Quality of Life
timeFrame: at 2, 4, 6, 8 weeks, 3 and 6 months, then every 6 months
measure: Progression free survival
timeFrame: up to 3 years
measure: Overall survival
timeFrame: up to 3 years
measure: Occurrence or progression of vertebral compression fracture (VCF)
timeFrame: up to 12 months
measure: Occurrence of radiation-induced myelopathy
timeFrame: up to 12 months
measure: Duration of pain relief
timeFrame: at 2, 4, 6, 8 weeks, 3 and 6 months
measure: Determination of rapidity of pain relief
timeFrame: at 2, 4, 6, 8 weeks, 3 and 6 months
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: UMC Utrecht
name: Helena M. Verkooijen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: van 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.