Stereotactic Body Radiotherapy Followed by Surgical Stabilization for Patients With Unstable Spinal Metastases (BLEND)

Stereotactic Body Radiotherapy Followed by Surgical Stabilization for Patients With Unstable Spinal Metastases: First-in-Man Study According to the IDEAL Recommendations

The aim of this study is to assess the feasibility and safety of combining stereotactic body radiotherapy (SBRT) and pedicle screw fixation in a 48-hour window for the treatment of painful unstable metastases of the thoracic and/or lumbar spine.

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis
• Intervention / Treatment: Procedure: BLEND

Detailed Description

Rationale: Sixty-five percent of cancer patients with terminal illness have bone metastases, with debilitating pain as devastating consequence. The spine is the most common location for bone metastases. Spinal cord compression is present in 10% of patients with vertebral metastases and aggravates pain and performance status even further. Standard treatment of unstable vertebral metastases consists of stabilizing surgery, followed by external beam radiotherapy (8 Gy) after two weeks. Although this approach is effective in 60-70% of patients, it is has several downsides. Firstly, because of the two weeks interval between surgery and external beam radiotherapy, necessary for sufficient wound healing, it takes a long time before radiotherapy induced pain relief is achieved. Scatter artifacts on planning computed tomography images caused by surgical implants prohibit high-resolution imaging and accurate targeting of the lesion. Multiple hospital visits (+/- 10) are needed for administration of external beam irradiation, and in about 30-40% of patients no adequate pain response is achieved. An alternative treatment strategy, which would lead to faster pain relief in a higher proportion of patients with less hospital visits, would be highly desirable from the patient's perspective.

Objective: To assess the feasibility and safety of combining stereotactic body radiotherapy (SBRT) and pedicle screw fixation in a 48-hour window for the treatment of painful unstable metastases of the thoracic and/or lumbar spine.

Study design: Prospective case series (13), first in man study, Phase I and II a study according to the IDEAL recommendations

Study population: All patients, male and female, with impending spinal stability requiring radiation therapy and surgical intervention at the University Medical Center Utrecht

Main study parameters/endpoints: The main outcome of this study is safety of the combined procedure, defined as grade 3 or higher treatment-induced toxicity according to common terminology criteria for adverse events (CTC-AE) 4.0 as a result of the procedure within 60 days after the surgery.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Painful metastases from solid tumors in the thoracic or lumbar spine needing surgical stabilization
• Histologic proof of malignancy
• Radiographic evidence of spinal metastases
• Karnofsky performance status ≤ 50
• Written informed consent

Exclusion Criteria:

• Multiple spinal metastases necessitating bridging more than five vertebral levels during surgery
• Previous surgery or radiotherapy to index lesion
• stereotactic body radiotherapy cannot be delivered (Bilsky score 2 and 3)
• Neurological deficits (ASIA C, B or A)
• Partial neurological deficits (ASIA D) with rapid progression (hours to days)
• Inability to lie flat on table for stereotactic body radiotherapy
• Non-ambulatory patients
• Patient in hospice or with < 3 months life expectancy
• Medically inoperable or patient refused surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BLEND; Combination of stereotactic bodyradiotherapy and surgical stabilization within 48 hours for the treatment of unstable spinal metastases.	Procedure: BLEND; Stereotactic bodyradiotherapy and surgical stabilization within 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events	Occurrence of adverse events grade 3/4 according to the common terminology criteria for adverse events (CTCAE) 4.0	first 90 days post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain response	Measurement of pain response to combined therapy according to consensus guidelines	first 90 days post treatment
Duration of pain relief	Measurement of duration of pain relief	first 90 days post treatment
Rapidity of pain relief	Measurement of rapidity of pain relief	first 90 days post treatment
Hospital stay	Measurement of length of hospital stay	first 90 days post treatment
Early mortality	Measurement of 30 days mortality	First 30 days post treatment
Neurological status	Measurement of neurological deterioration	First 90 days post treatment
Quality of life	Evaluation of quality of life	first 90 days post treatment
Survival	Overall survival	Time from inclusion until date of death from any cause assessed up to 100 months

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Investigators: Principal Investigator: Jorrit-Jan Verlaan, MD, PhD, UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: September 17, 2015
• First Submitted That Met QC Criteria: December 2, 2015
• First Posted (Estimate): December 7, 2015

Study Record Updates

• Last Update Posted (Actual): May 8, 2017
• Last Update Submitted That Met QC Criteria: May 5, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Palliative care; Spinal metastases; First in man; Stereotactic bodyradiotherapy; Surgical stabilisation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: NL51405.041.15