MR Guided Focused Ultrasound vs Radiotherapy for Palliative Pain Tx in Bone Metastases

Study Overview
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Brief Summary
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This is a prospective, single-center, randomized study directly comparing outcomes after MR guided high intensity focused ultrasound (MR HIFU) or external beam radiation therapy (EBRT) treatment of painful bone metastases.

Detailed Description
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The primary purpose of this study is to see if MR guided high intensity focused ultrasound (MR-HIFU) treats bone pain faster than the standard radiation therapy (External beam radiation therapy: EBRT) and to evaluate the patient's pain experience 14 days after completion of the treatment. The secondary purpose is to evaluate the outcomes of the pain, side effects, and quality of life and survival in the first 6 months after treatment.

Official Title
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MR Guided Focused Ultrasound Versus Radiotherapy for Palliative Pain Treatment in Patients With Bone Metastases

Conditions
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Bone Metastases

Intervention / Treatment
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* Procedure: MR- High intensity focused ultrasound
* Radiation: External beam radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Painful metastatic bone lesions, with NRS > 4 documented at screening visit Pain from target lesion is distinguishable from other lesions* Target lesion lovation is accessible for MR-HIFU and EBRT** Target lesion is visible om MR or CT imaging obtained < 3 months prior to screening, with a maximum diameter of 8 cm. Reasonable performance score (KPS > 50% or ECOG <3) Life expectancy > 3 months as determined by the study PI or referring oncologist Ability to understand and the willingness to personally sign the written IRB-approved informed consent document Solitary painful metastatic bone lesion or multiple metastatic lesions with one predominantly painful target lesion (≥2 points higher pain score than other lesions). e.g.: Extremities, pelvis (os pubis, os ilium, os ischium, sacrum, acetabulum), shoulders, in selected cases ribs and sternum Exclusion Criteria: Previous surgery, radiation, HIFU, or other local therapy on the target location Neurological symptoms due to nerve involvement of target lesion Need for surgery of targeted location due to (impending) pathological fracture Unavoidable critical structures or dense tissues in target area* Curative intention of treatment plan Patients with contraindication for MR imaging such as implanted metallic devices that are not MRI - safe, size limitations, claustrophobia, etc. Patients with known intolerance or allergy to MR contrast agent (gadolinium chelates) including advanced kidney disease (GFR <30mL/min/1.73 m^2) or on dialysis Pregnant and nursing patients will be excluded from the study because of a contraindication to administering MRI contrast agents to these patients Patients unable to receive general anesthesia, as determinded by anesthesiologist, study PI or referring oncologist Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (can be up to 4 hrs of total table time) via self report Participant enrolled in another clinical interventional study related to bone metastases treatment or pain relief treatment Clinically relevant medical history or physical findings that could interfere with the patient's safety as judged by the treating physician as judged by the operator. e.g.: nerve bundles, skin, extensive scarring, non-targeted bones, air (e.g. hollow viscera), (external) fixation device

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MR guided high intensity focused ultrasound (MR-HIFU)<br>MRHIFU treatment will be delivered using the ExAblate 2100 System (INSIGHTEC, Tirat Carmel, Israel), which is an FDA-approved device for pain palliation of bone metastases. | Procedure: MR- High intensity focused ultrasound<br>* The intervention treatment is MR-HIFU, which will be given as a standalone treatment. MRHIFU treatment will be delivered using the ExAblate 2100 System (INSIGHTEC, Tirat Carmel, Israel), which is an FDA-approved device for pain palliation of bone metastasesThe ExAblate focused ultrasound device operates in conjunction with an MRI machine. Gadavist is being administered intraveneously as contrast medium for MRI.<br>* Other names: MR-HIFU;|
| Active Comparator: External beam radiation therapy (EBRT)<br>Patients will undergo radiotherapy for painful bone metastases. | Radiation: External beam radiotherapy<br>* Standard of care for pain palliation of bone metastases consists of single fraction external beam radiotherapy of 8-16 Gray (Gy) or a multi-fraction regime of 20 Gy in 5 fractions, 24 Gy in 6 fractions or 30 Gy in 10 fractions. The radiation schedule is at the discretion of the treating radiation oncologist.<br>* Other names: EBRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that achieve a complete response (CR) or partial response (PR) | Complete response (CR): Complete response is defined as a pain score of zero at the treated site with no concomitant increase in analgesic intake (stable or reducing analgesics in daily oral morphine equivalents). Partial Response (PR): Partial response is to be defined as any of the following: Pain reduction of 2 or more points at the treated site on a 0-10 scale without analgesic increase; or analgesic dose reduction of 25% or more in daily morphine equivalent from baseline without an increase in pain. | 14 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-reported pain scores - Pain Diary | Patient reported pain scores will be based on a Numeric Rating Scale (NRS) (from 0 to 10) 0 = no pain and 10= worst pain. Assessed using the patient pain diary from treatment day to 1 month after completion treatment. | 1 month | 
| Patient-reported pain scores - BPI (Brief Pain Inventory) | The BPI measures pain interference on seven 0-10 integer subscales, as well as the mean of the seven subscales. | on baseline, at 2 and 4 weeks, and at 3 and 6 months | 
| Physician-reported adverse events | Assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0; we will report the number of pathologic fractures at the site of treatment | on baseline, at 2 and 4 weeks, and at 3 and 6 months | 
| Patient-reported quality of life - EORTC QLQ-BM22 | During follow up, patient will received quality of life questionnaire on baseline, at 2 and 4 weeks, and at 3 and 6 months after completion of treatment. | on baseline, at 2 and 4 weeks, and at 3 and 6 months | 
| Patient-reported quality of life - EORTC QLQ-C15-PAL | During follow up, patient will received quality of life questionnaire on baseline, at 2 and 4 weeks, and at 3 and 6 months after completion of treatment. | on baseline, at 2 and 4 weeks, and at 3 and 6 months | 
| Patient-reported quality of life - EQ-5D-5L | During follow up, patient will received quality of life questionnaire on baseline, at 2 and 4 weeks, and at 3 and 6 months after completion of treatment. | on baseline, at 2 and 4 weeks, and at 3 and 6 months | 
| Patient-reported quality of life - PGIC | During follow up, patient will received quality of life questionnaire on baseline, at 2 and 4 weeks, and at 3 and 6 months after completion of treatment. Patient Global Impression of Change scale has a single question with a 7 point likert scale about overall improvement after treatment assessing change in pain, from Much Better to Much Worse | on baseline, at 2 and 4 weeks, and at 3 and 6 months | 
| Local tumor control | Assessed using CT and/or MRI imaging at three and/or six months after completion of treatment | 3 and 6 months after completion of treatment | 
| Anxiety and depression scores | Assessed by the Hospital Anxiety and Depression Scale (HADS). This measures anxiety and depression separately on seven four-point (0-3) subscales, giving total scores from 0-21 for both constructs. | on baseline, at 2 and 4 weeks, and at 3 and 6 months |