Multicenter Study of Magnetic Resonance-guided High Intensity Focused Ultrasound for Pain Palliation of Bone Metastases

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of the Philips Sonalleve Magnetic Resonance Imaging-guided High Intensity Focused Ultrasound (MR-HIFU) device for treating painful bone metastases.

Detailed Description
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Magnetic Resonance Imaging-guided High Intensity Focused Ultrasound (MR-HIFU) is a non-invasive outpatient modality. In MR-HIFU, a specially designed ultrasound transducer is used to focus a beam of ultrasound energy into a small volume at a specific target site in the body. The focused beam is intended to produce therapeutic hyperthermia in the target field while only harmlessly warming the immediately surrounding tissue. Magnetic Resonance Imaging is used during the ultrasound treatment, both to focus the ultrasound beam on the target field and to perform real-time thermal mapping at and around the target. The Philips Sonalleve MR-HIFU system is expected to be efficacious in reducing pain scores in patients with painful bone metastases and in reducing their pain medication usage.

Official Title
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Magnetic Resonance-guided High Intensity Focused Ultrasound for Palliation of Painful Skeletal Metastases - a Multicenter Study

Conditions
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Bone Metastasis

Intervention / Treatment
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* Device: MR-HIFU treatment for pain palliation of bone metastases


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women with age ≥ 18 years Patient capable of giving informed consent and able to attend study visits Weight < 140kg Radiologic evidence of bone metastases from any solid tumor Diagnosis of dominant painful bone metastasis (Numerical Representative Scale (NRS) pain score ≥4), either refractory to standard of care (including radiotherapy and optimal pain medication) or standard of care is contra-indicated or refused by patient. Patient has been on stable pain medication for at least 1 week prior to HIFU treatment date Pain is localized to the targeted area, or is likely to be referred pain arising from the targeted area Patient has 1-3 painful lesions, and only the most painful lesion will be treated Intended Target Volume accessible for MR-HIFU procedure Target lesion maximum dimension ≤ 8cm Intended target volume visible by non-contrast MRI Distance between target and skin ≥ 1cm Patient is able to communicate sensation during MR-HIFU treatment MR-HIFU treatment date ≥ 4 weeks from last local treatment of the target lesion Exclusion Criteria: Planned treatment lesion is a primary bone tumor or due to lymphoma, multiple myeloma, or leukemia. Communication barrier present Patient enrolled in another clinical study related to bone metastases treatment or pain relief treatment Unable to tolerate required stationary position during treatment Need for surgical stabilization in case of (impending) fracture (lytic lesion in weight-bearing bone larger than 50% of bone diameter) Pregnant woman Pain related to target lesion is predominantly due to fracture or impending fracture Pain related to target lesion is due to involvement of a neighboring major nerve by the metastatic tumor (cord or nerve compression) Target < 3cm from bladder / bowel / nerve along the beam path and < 1cm in the plane orthogonal to the beam Target in contact with hollow viscera Target located in skull, joints, ribs (when HIFU beam overlapping with lung), spine (excluding sacrum which is allowed) or sternum Scar along proposed HIFU beam path Internal or external fixation device along the proposed HIFU beam path or at the target MRI contraindicated (e.g. paramagnetic implants, pacemaker, claustrophobia) MRI contrast agent contraindicated (e.g. previous anaphylaxis or Glomerular Filtration Rate (GFR) < 30 ml/min/1.73m2) Sedation contraindicated Previous surgery or minimally invasive treatment at targeted site Clinically relevant medical history or abnormal physical findings that could interfere with the safety of the participant as judged by the treating physician or investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MR-HIFU treatment<br>Subjects undergo a MR-HIFU treatment for pain palliation of bone metastases on their most painful metastasis. | Device: MR-HIFU treatment for pain palliation of bone metastases<br>* A treatment session with the Philips Sonalleve MR-HIFU device for bone pain palliation with high-intensity focused ultrasound.<br>* Other names: Philips Sonalleve MR-HIFU Bone Pain Palliative Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain response to therapy | Pain is measured using the Brief Pain Inventory (BPI) questionnaire. Patients are categorized into: Complete response (CR): Pain score 0 without analgesic increase Partial response (PR): Pain reduction of 2 or more without analgesic increase; or analgesic reduction of 25% without pain increase Pain Progression (PP): Pain increase of 2 or more with stable analgesic use; or increase of 25% or more in analgesic use, with pain score stable or 1 point above baseline No response corresponds to all other cases Patients with PR or CR at 30 days are considered responders to therapy. | 30 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of Adverse Events | Total number of complications and adverse events, including the number of unintended lesions that occur as a result of treatment with MR-HIFU. | within the first 90 days within treatment | 
| Quality of Life (as measured by questionnaire) | Quality of Life will be measured at the given time points using a dedicated questionnaire for patients in palliative care: the European Organisation on Research and Treatment of Cancer (EORTC) C15-PAL questionnaire. | at day 0 before treatment, and at 7, 14, 30, 60 and 90 days after treatment | 
| Subgroup analysis: pain response in radiation naïve patients | Assessment of positive response on pain (as determined by the Primary Outcome Measure) will be documented separately for radiation naïve patients and radiation failure patients, and a comparison between the two sub-groups will be performed. | 30 days after treatment | 
| Temporal evolution of pain response during the first 30 days after treatment | Patients are given a diary to complete during the first 30 days after treatment, which documents their daily pain level on a 0-10 scale and their pain medication usage. | during the first 30 days after treatment |