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

Study Purpose

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.#46; 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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)

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06613295
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Cancer Research Antwerp
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Charlotte Billiet, MD, PhD
Principal Investigator Affiliation	ZAS Augustinus
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Belgium
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Solid Tumor, Spinal Neoplasms, Spinal Tumor

Additional Details

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)

Arms & Interventions

Arms

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.

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.

Interventions

Radiation: - SABR

SABR

Procedure: - Separation surgery

Separation surgery

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