Trial Information

Summary: A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Treatment of Metastatic Bone Tumors for the Palliation of Pain in Patients Who are not Candidates for Radiation Therapy

The objective of this trial is to evaluate the effectiveness and safety of ExAblate (MR guided Focused Ultrasound, MRgFUS) for the palliation of pain from metastatic bone tumors in patients who are not suitable candidates to receive additional radiation therapy. ExAblate MRgFUS uses ultrasound to non-invasively (without surgical cutting) treat tissue that might otherwise be treated with radiation or be surgically removed. ExAblate treatment is approved for the treatment of uterine fibroids, but its use for the palliation of pain from bone metastases is experimental. The study hypothesis is that ExAblate is safe and effective in the treatment of pain resulting from metastatic bone tumors in patients that did not respond to radiation treatment or who are otherwise unsuitable for radiation treatment, with a low incidence of co-morbidity. Qualifying patients will be randomly assigned to the ExAblate Test Group or Sham Control Group in a ratio of 3:1. Study candidates will have well defined localized pain clearly associated with no more than 3 bone metastasis. However, one of painful spots must be more painful than any others. All qualifying patients will complete an MRI exam on treatment day after a run-in period to optimize patient pain meds at baseline in relation to patient pain, functionality and side effects of pain medications. After treatment, all continuing patients of both study arms will be followed for 3 months to assess their pain status and their quality of life. Data regarding dosage and frequency of analgesic intake for the management of metastatic bone tumor induced pain will be collected. Relevant cost data will be collected in order to enable an assessment of the total cost of the procedure. Follow-up visits to assess pain, pain medications, quality of life, adverse events and health costs will be completed at 1 and 3 days, 1 and 2 weeks and 1,2 and 3 months post-ExAblate or Sham treatment. Sham Control Group patients who meet the protocol definition of treatment failure during follow-up may be offered ExAblate treatment and repeat the follow-up visits. Promising results from preliminary study results indicate that ExAblate treatment may be an effective therapy for reducing pain caused by bone metastases in patients who are not candidates for additional radiation therapy.

Study 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 and are radiation failures:
  
  • Radiation failure candidates are those 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, and those patients who refuse additional radiation therapy,
• Patients who refuse other accepted available treatments such as surgery or narcotics for pain alleviation.
• Patient with NRS (0-10 scale) pain score ≥ 4 irrespective of medication
• Targeted tumor (treated) size up to 8 cm in diameter
• Patient whose targeted (treated) lesion is on bone and 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
• At least 2 weeks since 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 3 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).

Study Exclusion Criteria

• Patients who either
  • Need surgical stabilization of the affected bony structure (>7 fracture risk score, see Section 7.3)
    OR
  • Targeted tumor is at an impending fracture site (>7 on fracture risk score, see Section 7.3).
    OR
  • Patients with surgical stabilization of tumor site with metallic hardware
• More than 3 painful lesions, or more than 1 requiring immediate localized treatment
• Targeted (treated) tumor is in a vertebral body or in the posterior aspects of the cervical part of the vertebral column.
• 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 (weight >250 pounds), 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 < 70 (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 receiving chemotherapy or radiation within the last 2 weeks
• Patients unable to communicate with the investigator and staff.
• Patients with persistent undistinguishable pain (pain source unidentifiable)
• Targeted (treated) tumor size ≥ 8 cm in diameter
• Patient whose lesion is on bone and is < 10-mm from the skin
• Targeted (treated) 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.

If you would like to learn more about participating in this study, please send an e-mail message using the form below.