Randomized Trial on Same-day SBRT and Surgical Stabilization for Symptomatic Spinal Metastases

Spinal Metastases Clinical Trial

— BLEND  

Official title:

Stereotactic Body Radiotherapy and pedicLE Screw fixatioN During One Hospital Visit for Patients With Painful Unstable Spinal Metastases: A Randomized Trial (BLEND)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05575323
• Other study ID #: NL80847.041.22
• Status: Recruiting
• Phase: N/A
• Start date: October 15, 2022
• Est. completion date: June 30, 2027

Study information

• Verified date: February 2024
• Source: UMC Utrecht
• Contact: Roxanne Gal, PhD
• Phone: +31 88 75 69624
• Email: R.Gal[@]umcutrecht.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The BLEND RCT aims to evaluate the (cost-)effectiveness of same-day SBRT and surgical stabilization with or without decompression for the treatment of symptomatic, unstable spinal metastases on physical functioning four weeks after the start of treatment, compared with the standard of care (surgery followed by radiotherapy as soon as the wound healed sufficiently).

Description:

Rationale: Currently, patients with unstable spinal metastases receive surgical stabilization with/without decompression followed by conventional radiotherapy (cRT) or stereotactic body radiotherapy (SBRT) as soon as wound healing allows (at least 1 week). Advancements in radiotherapy techniques makes preoperative radiotherapy possible with sparing of the soft tissues overlying the surgical field. This makes it possible to shorten or even eliminate the time interval between surgery and radiotherapy. This will result in shorter and less hospital visits, earlier pain relief from irradiation, and faster return to systemic therapy without an increase in wound complications due to the short interval between surgery and radiotherapy.

Objective: The BLEND RCT aims to evaluate the (cost-)effectiveness of same-day SBRT and surgery for the treatment of symptomatic, unstable spinal metastases on physical functioning four weeks after the start of the treatment, compared with the standard of care (surgery followed by radiotherapy, i.e., CRT or SBRT).

Study design: A phase II randomized controlled trial within the PRospective Evaluation of interventional StudiEs on boNe metastases (PRESENT) cohort including patients with bone metastases, according to the Trials within Cohorts (TwiCs) design.

Study population: Patients with symptomatic (cervical, thoracic and/or lumbar) spinal metastases and impending spinal instability requiring radiotherapy and surgical stabilization with or without decompression.

Intervention: SBRT (with active dose-sparing of the surgical site) and surgical stabilization with or without decompression within 24 hours. The control group will receive the standard of care, which is surgical stabilization with or without decompression followed by cRT or SBRT as soon as the wound is healed sufficiently.

Main study endpoints: The primary endpoint is physical functioning at four weeks after the start of the treatment. Secondary endpoints are pain response, duration of pain relief, length of hospital stay, time to return to systemic therapy, neurological deterioration, adverse events (e.g. wound complications), quality of life and survival. In addition, we will study the cost-effectiveness.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Symptomatic (cervical, thoracic and/or lumbar) spinal metastases from solid tumors and (impending) spinal instability requiring radiotherapy and surgical decompression and/or stabilization

• Histologic proof of malignancy or radiographic/clinical characteristics indicating malignancy beyond reasonable doubt

• Radiographic evidence of spinal metastases

• Participation in PRESENT cohort, including consent for randomization into future trials

• Fit for (radio)surgery

• Age >18 years

• Written informed consent

Exclusion Criteria:

• SBRT cannot be delivered, e.g. in patients who cannot lie on the treatment table because of pain

• Routine surgical decompression and/or stabilization and radiotherapy cannot be performed, e.g., multiple spinal metastases requiring surgical bridging of more than five vertebral levels and/or requiring radiotherapy on more than one location

• Prior surgery or radiotherapy to the index level(s)

• Multiple myeloma

• Neurological deficits (ASIA C, B or A), or partial neurological deficits (ASIA D) with rapid progression (hours to days)

• Treated with Bevacizumab and other medication with long half-life that interferes with radiotherapy

• Life expectancy of less than 3 months

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Spinal Metastases

Intervention

Other:
• Same-day SBRT and spinal surgery
SBRT and surgical stabilization with or without decompression within 24 hours
• Standard of care
Surgical stabilization with or without decompression followed by cRT or SBRT as soon as the wound is healed sufficiently

Locations

Country	Name	City	State
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cost-effectiveness	If same-day SBRT and surgery is more costly and more effective than the standard of care, an incremental cost-effectiveness ratio (ICER) will be calculated by dividing the extra QALYs by the extra effects. This will give an estimation of the extra costs that are needed to gain one QALY. If this is below the cost-effectiveness threshold, same-day SBRT and surgery is deemed cost-effective. If either same-day SBRT and surgery or the standard of care is less costly and more effective than its alternative, it dominates this alternative and no ICER is necessary to determine cost-effectiveness.	up to 12 months
Primary	Physical functioning	Physical functioning is a functional scale from the EORTC QLQ-C15-PAL questionnaire. Patients rate each item on a 4-point Likert scale ranging from 1 (not at all) to 4 (very much), and scale scores were linearly transformed to a 0-100 scale. A higher score on the functional scale indicates better functioning.	at 4 weeks after the start of treatment
Secondary	Pain response	Pain response is defined as 1) a decline in worst pain score of at least two points on an NRS of ten at the treated site without increase in analgesic use, or 2) an analgesic decrease of at least 25% without an increase in pain score. Worst pain score will be measured with the Brief Pain Inventory.	at 2, 4, 6 and 8 weeks, and 3 months after the start of treatment
Secondary	Duration of pain relief	Duration of pain relief as measured by the Brief Pain Inventory (BPI).	up to 3 months
Secondary	Duration of hospital stay	Duration of hospital stay in days	up to 3 months
Secondary	Days until return to systemic treatment	Days until return to systemic treatment	up to 12 months
Secondary	Neurological deterioration	Occurrence of neurological deterioration is defined as deterioration of more than one grade on the American Spinal Cord Injury Association (ASIA) scale as measured by physical examination by a neurologists or trained ASIA physician.	up to 12 months
Secondary	Change in health-related quality of life	Change in patient-reported health-related quality of life is measured by the EORTC QLQ-C15-PAL at predefined time intervals.	at 4 and 8 weeks, and 3 and 6 months after the start of treatment
Secondary	Change in health-related quality of life	Change in patient-reported health-related quality of life is measured by the EORTC QLQ-BM22 at predefined time intervals.	at 4 and 8 weeks, and 3 and 6 months after the start of treatment
Secondary	Local control	Local control according to routine imaging and electronic patient chart	up to 12 months
Secondary	Adverse events	Adverse events are defined as any undesirable experience occurring to a patient during the study, (likely) related to the experimental treatment procedure. All adverse events during hospital stay will be evaluated using the most recent version of the National Cancer Institute Common Toxicity Criteria of Adverse Events (CTCAE; version 5.0, version 6.0 when available at the start of the study) for acute and late toxicity. All adverse events after hospital discharge reported spontaneously by the patient or observed by the investigator or research team will be recorded up to three months after the treatments.	up to 3 months
Secondary	Progression free survival	Progression free survival is defined as time between treatment and first sign of progression of disease.	up to 12 months
Secondary	Overall survival	Overall survival is defined as time between treatment and death from any cause.	up to 12 months