A Phase IV Post Approval Clinical Study of ExAblate Treatment of Metastatic Bone Tumors for the Palliation of Pain

As part of the PMA # P110039 review process and approval, InSightec was requested to conduct a post-approval study. Patients will be treated following the approved commercial treatment guidelines.

For this study, participating sites will use the ExAblate device for the administration of the ExAblate treatment. This study will be performed on either 1.5T or 3T MR scanners.

For this study, a total of 70 patients meeting the approved commercial guidelines will be enrolled and treated with the ExAblate system at from 7 to 10 sites. The proportion of responders is expected to be at least 30% greater than the proportion of subjects experiencing pain progression (i.e., 60% vs. 30%). Additionally, at the 3 month visit, an analysis of both the safety and efficacy profiles will be compared to the original PMA pivotal study group.

Inclusion criteria

• Men and women age 18 and older
• Patients who are able and willing to give consent and able to attend all study visits
• Patients who are suffering from symptoms of bone metastases or multiple myeloma bone lesions:
• Patients who have received radiation without adequate relief from metastatic bone pain as determined by the patient and treating physician
• those for whom their treating physician would not prescribe radiation or additional radiation treatments
• patients who refuse additional radiation therapy.
• Patient with NRS (0-10 scale) pain score ≥ 4 irrespective of medication
• Targeted bone/tumor interface are ExAblate device accessible and are located in ribs, extremities (excluding joints), pelvis, shoulders and in the posterior aspects of the following spinal vertebra: Lumbar vertebra (L3 - L5), Sacral vertebra (S1 - S5)
• Targeted bone/tumor interface (most painful lesion) size up to 55 cm2 in surface area
• Patient whose targeted (treated) lesion is on bone and the interface between the bone and lesion is deeper than 10-mm from the skin.
• Targeted (treated) tumor clearly visible by non-contrast MRI, and ExAblate MRgFUS device accessible
• Able to communicate sensations during the ExAblate treatment
• Patients on ongoing chemotherapy regimen at the time of eligibility:

• with same chemotherapy regime (as documented from patient medical dossier), And
• Worst pain NRS still ≥ 4 And
• do NOT plan to initiate a new chemotherapy for pain palliation should be eligible for the study.

Note: Planned multiple courses of chemotherapy are not considered New Chemotherapy.

• No radiation therapy to targeted (most painful) lesion in the past two weeks Bisphosphonate intake should remain stable throughout the study duration.
• Patients will have from 1 to 5 painful lesions and only the most painful lesion will be treated.
• Patients with persistent distinguishable pain associated with 1 site to be treated (if patient has pain from additional sites, the pain from the additional sites must be evaluated as being less intense by at least 2 points on the NRS compared to the site to be treated).

Exclusion criteria

• Patients who either
• Need surgical stabilization of the affected bony structure (>7 fracture risk score, see Section 7.4) OR
• Targeted tumor is at an impending fracture site (>7 on fracture risk score, see Section 7.4).

OR

• Patients with surgical stabilization of tumor site with metallic hardware
• More than 5 painful lesions, or more than 1 requiring immediate localized treatment
• Targeted (treated) tumor is in the skull
• Patients on dialysis
• Patients with life expectancy < 3-Months
• Patients with an acute medical condition (e.g., pneumonia, sepsis) that is expected to hinder them from completing this study.
• Patients with unstable cardiac status including:
• Unstable angina pectoris on medication
• Patients with documented myocardial infarction within six months of protocol entry
• Congestive heart failure requiring medication (other than diuretic)
• Patients on anti-arrhythmic drugs
• Severe hypertension (diastolic BP > 100 on medication)
• Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
• Patients with an active infection or severe hematological, neurological, or other uncontrolled disease.
• Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium or Magnevist) including advanced kidney disease
• KPS Score < 60 (See "Definitions" below)
• Severe cerebrovascular disease (multiple CVA or CVA within 6 months)
• Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (approximately 2 hrs.)
• Target (treated) tumor is less then 1cm from nerve bundles, bowels or bladder.
• Are participating or have participated in another clinical trial in the last 30 days
• Patients initiating a new chemotherapy regime for pain purposes only, or radiation (for the targeted most painful lesion) within the last 2 weeks Note: Planned multiple courses of chemotherapy are not considered New Chemotherapy.
• Patients unable to communicate with the investigator and staff.
• Patients with persistent undistinguishable pain (pain source unidentifiable of the targeted lesion)
• Patient whose bone-lesion interface is < 10-mm from the skin
• Targeted (most painful) tumor NOT visible by non-contrast MRI,
• Targeted (most painful) tumor Not accessible to ExAblate
• The targeted tumor is less than 2 points more painful compared to other painful lesions on the site specific NRS.