A Pivotal Study to Evaluate the Effectiveness and Safety of ArcBlate Palliative Treatment for Patients With Painful Bone Metastases

Pain palliation of bone metastasis through localized denervation by thermal ablation.

Inclusion Criteria:

• Provisional Screening (Screening 1):

  1. Men and women aged 18 and older.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at enrollment.
  3. Patients who are able and willing to give consent and able to attend all study visits.
  4. Patients who are suffering from painful bone metastases.
  5. Patients who refuse other accepted available treatments such as surgery or radiotherapy for pain palliation.
  6. Patient with NRS (0-10 scale) pain score ≥ 4 irrespective of medication.
  7. Able to communicate sensations during the ArcBlate MRgHIFU treatment.
  8. Patients on ongoing systemic anticancer treatment for at least 2 weeks before treatment:

• with same systemic anticancer treatment (as documented from patient medical dossier), And

• worst pain NRS still ≥ 4, And

• do NOT plan to initiate a new chemotherapy for pain palliation throughout the study duration.

  (9) No radiation therapy to targeted (most painful) lesion in the past two weeks before treatment.

  (10) Bisphosphonate intake should remain stable throughout the study duration. (11) Patients will have from 1 to 5 painful lesions and only the most painful lesion will be treated.

  (12) 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).

• MRI Screening (Screening 2):

  1. Targeted tumor(s) are ArcBlate MRgHIFU 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).
  2. Patient whose targeted (treated) lesion is on bone and the interface between the bone and lesion is deeper than 10-mm from the skin.
  3. Targeted (treated) tumor clearly visible by non-contrast MRI, and ArcBlate MRgHIFU accessible.

• Sonication Screening (Screening 3):

  1. Subjects could tolerate planned test sonications per randomized treatment.

Exclusion Criteria:

• Provisional Screening (Screening 1):

  (1) Patients who either

• need surgical stabilization of the affected bony structure (>7 fracture risk score), Or

• targeted tumor is at an impending fracture site (>7 on fracture risk score), Or

• patients with surgical stabilization of tumor site with metallic hardware. (2) Targeted (treated) lesion is in the skull. (3) Patients on dialysis. (4) Patients with life expectancy < 3-Months. (5) Patients with an acute medical condition (e.g., pneumonia, sepsis) that is expected to hinder them from completing this study.

  (6) 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. (7) Severe hypertension (diastolic blood pressure > 100 mmHg on medication). (8) Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations (unable to fit into ArcBlate MRgHIFU), etc.

  (9) Patients with an active infection or severe hematological, neurological, or other uncontrolled disease.

  (10) Known intolerance or allergies to the MRI contrast agent (e.g., Gadolinium or Magnevist) and Computed Tomography (CT) contrast agent including advanced kidney disease.

  (11) Severe cerebrovascular disease (multiple CerebroVascular Accident (CVA) or CVA within 6 months).

  (12) Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (approximately 2 hrs.).

  (13) Are participating or have participated in another clinical trial in the last 30 days.

  (14) Patients initiating a new chemotherapy regime, or radiation (for the targeted most painful lesion) within the last 2 weeks before treatment.

  (15) Patients unable to communicate with the investigator and staff. (16) Patients with persistent undistinguishable pain (pain source unidentifiable).

  (17) The targeted tumor is less than 2 points more painful compared to other painful lesions on the site specific NRS.

  (18) Patients with calcified treatment area. (19) Pregnant women.

• MRI Screening (Screening 2):

  1. Target (treated) lesion is less than 10-mm from nerve bundles, bowels or bladder.
  2. Extensive scarring in the energy path of the planned treatment area