Separation Surgery Followed by Stereotactic Ablative Body Radiotherapy (SABR) Versus SABR Alone for Spinal Metastases (SABR-MESCC)

Separation Surgery Followed by Stereotactic Ablative Body Radiotherapy Versus Stereotactic Ablative Body Radiotherapy Alone for Spinal Metastases Invading the Spinal Canal: a Randomised, Non-inferiority Trial

This is a non-inferiority, randomised controlled trial to investigate the effect of stereotactic ablative body radiotherapy (SABR) compared to separation surgery followed by SABR in ambulatory patients with malignant epidural spinal cord compression (MESCC).

The primary objective of the project is investigating the effect of SABR compared to separation surgery followed by SABR in ambulatory patients with MESCC on retaining ambulatory function. The primary endpoint of the study is ambulatory function 3 months post treatment defined as: being able to walk 10m without aid; being able to walk 10m with aid (cane, rollator, one persons help, …); not being able to walk. Secondary outcomes are local control, progression free survival, early and late adverse effects, quality of life, effect on pain and need for reintervention.

The aim is to randomise 128 patients 1:1 to either "separation surgery" followed by SABR (5x 8.0 Gy postoperative) (control arm) vs. SABR alone (5x 8.0 Gy) (study arm).

Patients will be evaluated at 3 and 6 months after treatment with MRI scan, quality of life questionnaires, anamnestic and clinical evaluation at clinical follow ups for assessment of ambulatory function, acute and late toxicity and need for reintervention. Moreover, at 6 weeks, 12 months and 24 months after treatment a teleconsult for assessment of ambulatory function, and need for reintervention will be performed.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Spinal Tumor; Spinal Neoplasms
• Intervention / Treatment: Radiation: SABR; Procedure: Separation surgery

Detailed Description

In this study, patients with malignant epidural spinal cord compression (MESCC), Bilsky grade 1c, 2 and 3 who are ambulatory with or without aid (rollator, cane, one persons help) will be treated by separation surgery followed by SABR (5x 8.0 Gy postoperative) (control arm) or SABR alone (5x 8.0 Gy) (study arm). The primary objective of the study is investigating the effect of SABR compared to separation surgery followed by SABR in ambulatory patients with MESCC on retaining ambulatory function. The primary endpoint of the study is ambulatory function 3 months post treatment defined as: being able to walk 10m without aid; being able to walk 10m with aid (cane, rollator, one persons help, …); not being able to walk. Secondary outcomes are local control, progression free survival, early and late adverse effects, quality of life, effect on pain and need for reintervention.

For each participant, the study starts once written informed consent is provided and is composed by 4 study phases: a screening phase, randomisation, a treatment phase and a follow-up phase.

The screening phase will allow for assessment of subject eligibility before randomisation and treatment. Demographic data, disease and spinal metastases characteristics and previous anticancer therapies will be recorded. Once all screening procedures are completed, eligibility will be determined according to the inclusion/exclusion criteria. Randomisation will be performed in a 1:1 ratio to the control arm (separation surgery followed by SABR) and the study arm (SABR) using an electronic randomisation tool in the eCRF.

Treatment will be aimed to start as soon as possible, but certainly within 21 days after randomisation (surgery or upfront SABR). Surgical planning is done by the treating neurosurgeon in the participating center where the patient was included. Image-guided fractionated SABR using a SIB technique to the high-dose PTV will be delivered in 5 fractions of 8 Gy to a total of 40 Gy and to the conventional-dose PTV delivered simultaneously in 5 fractions of 4 Gy to a total of 20 Gy.

At 6 weeks (+/-1 week) after the last RT session following information will be obtained (preferentially by digital consult):

1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, …), not being able to walk
2. WHO performance status
3. Acute and late toxicity assessment: as measured with CTCAE version 5.0
4. Need for re-intervention, date and type of reintervention (surgery or radiotherapy), reason (wound infection, neurologic decline, loss of ability to walk or other)
5. Pain response: VAS pain score
6. Survival data (survival status, date of death, primary cause of death)

At 3 and 6 months (+/-3 weeks) after the last RT session following information will be obtained by physical or digital consult:

1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, …), not being able to walk
2. WHO performance status
3. Concomitant medications and systemic anticancer therapies
4. QoL according to the EORTC QLQ-C15 & BM22 questionnaires
5. Acute and late toxicity assessment: as measured with CTCAE version 5.0

7. Need for re-intervention, date and type of reintervention (surgery or radiotherapy), reason (wound infection, neurologic decline, loss of ability to walk or other) 6. Pain response: VAS pain score 7. Physical examination: body weight 8. Local control 9. Survival data (survival status, date of death, primary cause of death)

At 12 and 24 months (+/-3 weeks) after the last RT session following information will be obtained (preferentially by digital consult):

1. Ambulatory status defined as: being able to walk 10m without aid, being able to walk 10m with aid (cane, rollator, one persons help, …), not being able to walk
2. Need for re-intervention, type of reintervention
3. Survival data (survival status, date of death, primary cause of death)
4. Local control (only if information is available in medical record as per standard of care)

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charlotte Billiet, MD, PhD; Phone Number: 03234433759; Email: gza.cancertrials@zas.be

Study Locations

• Belgium
  • Aalst, Belgium
    • Not yet recruiting
    • OLVZ Aalst
    • Contact: Samuel Bral, MD; Phone Number: 32 053728656; Email: samuel.bral@olvz-aalst.be
    • Contact: Samuel Bral
  • Brasschaat, Belgium
    • Not yet recruiting
    • AZ KLINA
    • Contact: Ruben Van Den Brande, MD; Phone Number: 32 036505092; Email: ruben.vandenbrande@azklina.be
    • Contact: Ruben Van Den Brande
  • Edegem, Belgium
    • Not yet recruiting
    • UZA
    • Contact: Marika Rasschaert, MD; Phone Number: 32 038212441; Email: marika.rasschaert@uza.be
    • Contact: Marika Rasschaert
  • Genk, Belgium
    • Recruiting
    • ZOL
    • Contact: Evelyn Van de Werf, MD; Phone Number: 32 011337918; Email: evelyn.vandewerf@zol.be
    • Contact: Evelyn Van de Werf
  • Hasselt, Belgium
    • Not yet recruiting
    • Jessa
    • Contact: Katleen Verboven, MD; Phone Number: 32 011337918; Email: katleen.verboven@jessazh.be
    • Contact: Katleen Verb
  • Kortrijk, Belgium
    • Not yet recruiting
    • AZ Groeninge
    • Contact: Isabelle Kindts, MD; Phone Number: 32 056633943; Email: isabelle.kindts@azgroeninge.be
    • Contact: Isabelle Kindts
  • Mechelen, Belgium
    • Not yet recruiting
    • Az Sint-Maarten
    • Contact: Julie van der Veen, MD; Phone Number: 32 015891664; Email: julie.van.der.veen@emmaus.be
    • Contact: Julie van der Veen
  • Sint-Niklaas, Belgium
    • Recruiting
    • VITAZ
    • Contact: Erik Van de Kelft, MD; Phone Number: 32 037607565; Email: erik.vandekelft@vitaz.be
    • Contact: Erik Van de Kelft
  • Wilrijk, Belgium
    • Recruiting
    • GZA
    • Contact: Charlotte Billiet, MD; Phone Number: 32 034433759; Email: charlotte.billiet@gza.be
    • Contact: Charlotte Billiet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of a solid malignant tumour (preferentially histologically proven;alternatively obtained by spinal surgical procedure)
• Age 18 years or older
• Histological, radiological or scintigraphical evidence of spinal metastasis (no limitation in the number of sites of metastases)
• Spinal instability neoplastic score (SINS) <13 (i.e. no need for stabilisation of the spine) (see Appendix 6)
• Spinal metastasis with MESCC: ESCC grade 1c, 2 and 3 (see Appendix 7)
• Ambulatory: being able to walk 10m without aid or with aid (cane, rollator, one persons help).
• Life expectancy estimated to be at least 3 months.
• World Health Organization (WHO) Performance Status of 0-2 (some help) (see Appendix 3)
• Patient has given written informed consent.

Exclusion Criteria:

• Contra indication for MRI scan (e.g. pacemaker)
• Previous RT or surgery at the level of the affected vertebrae
• Non-solid primary tumours (e.g. lymphoma, multiple myeloma, germ cell tumours)
• Non ambulatory at presentation
• More than 3 affected vertebrae in one target site
• More than 2 treatment sites
• SINS ≥ 13 (unstable spine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Separation surgery followed by stereotactic ablative body radiotherapy; Surgery will take place within 21 days after randomisation. Surgical planning is done by the treating neurosurgeon in the participating center where the patient was included. The goal of separation surgery for intraspinal MESCC is to remove intraspinal epidural disease to allow a margin between the spinal cord (or cauda equina) and the treated radiotherapy volume, and to provide histological diagnosis or confirmation of the metastasis. The decompression should be as minimal invasive as possible, i.e. only intraspinal tumour tissue should be removed, while preserving as much as possible all of surrounding spinal structures. Separation surgery must be followed by SABR after minimum 2 and maximum 4 weeks postoperatively. Image-guided fractionated SABR using a SIB technique to the high-dose PTV will be delivered in 5 fractions of 8 Gy to a total of 40 Gy and to the conventional-dose PTV delivered simultaneously in 5 fractions of 4 Gy to a total of 20 Gy.	Radiation: SABR; SABR; Procedure: Separation surgery; Separation surgery
Experimental: Stereotactic ablative body radiotherapy; SABR will start within 21 days of randomisation. Image-guided fractionated SABR using a SIB technique to the high-dose PTV will be delivered in 5 fractions of 8 Gy to a total of 40 Gy and to the conventional-dose PTV delivered simultaneously in 5 fractions of 4 Gy to a total of 20 Gy.	Radiation: SABR; SABR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of ambulant patients at 3 months	The ambulatory status is scored binary (without or with aid vs not being able to walk)	3 Months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence rate	Time between date of study registration and date of local recurrence	Up to 24 months post treatment
Time to loss of ambulation	Time between date of study registration and date of loss of ambulation (in days)	Up to 24 months post treatment
Progression free survival (PFS)	Time between date of study registration and date of local recurrence	Up to 24 months post treatment
Overall survival	Time between date of study registration and date of death of any cause or last follow-up	Up to 24 months post treatment
Number of patients with re-intervention and time to re-intervention (surgery, RT, …)	Time between date of treatment and date of re-intervention	Up to 24 months post treatment
Acute and late toxicity	Incidence of Adverse Events as assessed by the CTCAE version 5.0	Up to 6 months post treatment
Quality of life measurement by QLQ-BM22 and QLQ-C15-PAL questionnaires	Difference in QLQ-BM22 and QLQ-C15-PAL scale scores	Up to 6 months post treatment
Pain response (VAS score)	Improvement by ≥ 2 points on the pain (VAS score) at the treatment site	Up to 6 months post treatment

Collaborators and Investigators

• Sponsor: Cancer Research Antwerp
• Investigators: Principal Investigator: Charlotte Billiet, MD, PhD, ZAS Augustinus

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2022
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Musculoskeletal Diseases; Spinal Cord Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Spinal Diseases; Bone Diseases; Bone Neoplasms; Spinal Cord Neoplasms; Spinal Neoplasms
• Other Study ID Numbers: CTO21003GZA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No