A Feasibility Study to Evaluate the Safety and Initial Effectiveness of ExAblate MR Guided Focused Ultrasound Surgery in the Treatment of Pain Resulting From Metastatic Bone Tumors With the ExAblate 2100 Conformal Bone System
18 Years
N/A
Both
Bone Metastases
Trial Information
A Feasibility Study to Evaluate the Safety and Initial Effectiveness of ExAblate MR Guided Focused Ultrasound Surgery in the Treatment of Pain Resulting From Metastatic Bone Tumors With the ExAblate 2100 Conformal Bone System
Bone is the third most common organ involved by metastatic disease behind lung and liver
[6]. In breast cancer, bone is the second most common site of metastatic spread, and 90% of
patients dying of breast cancer have bone metastasis. Breast and prostate cancer metastasize
to bone most frequently, which reflects the high incidence of both these tumors, as well as
their prolonged clinical courses. Post-cancer survival has increased with improvement in
early detection and treatments. As a consequence, the number of patients developing
metastatic bone disease during their lifetime has also increased.
Current treatments for patients with bone metastases are primarily palliative and include
localized therapies (radiation and surgery), systemic therapies (chemotherapy, hormonal
therapy, radiopharmaceutical, and bisphosphonates although the primary goal of the use of
these therapies are often to address the disease itself), and analgesics (opioids and
non-steroidal anti-inflammatory drugs). Recently, radiofrequency ablation has been tested
as a treatment option for bone metastases [8]. Currently, an off label use of Cryoablation
techniques are being tested as another alternative for bone Mets palliation. The main
goals of these treatments are improvement of quality of life and functional level. These
goals can be further described:
1. Pain relief
2. Preservation and restoration of function
3. Local tumor control
4. Skeletal stabilization
Treatment with external beam radiation therapy (EBRT) is the standard of care for patients
with localized bone pain, and results in the palliation of pain for many of these patients.
Twenty to 30% of patients treated with radiation therapy do not experience pain relief
[9-13]. Re-treatment rates are generally reported in the range of 10-25%. Many patients
with relapsed pain or poor response to initial radiation may be lost to follow up or may not
be referred back to oncologists for consideration of re-radiation. In addition to relapse
and re-treatment, there is an increased risk of pathologic fracture in the peri-radiation
period. The fracture rate reported in radiation studies is generally in the range of 1% to
8%. The hyperemic response weakens the adjacent bone and increases the risk of spontaneous
fracture. Furthermore, patients who have recurrent pain at a site previously irradiated may
not be eligible for further radiation therapy secondary to limitations in normal tissue
tolerance. Hesitation on the part of physicians to use a larger dose may be related to
increased long-term toxicity. Larger radiation dose produces a greater risk of
complications such as fibrosis of normal soft tissue, which can cause a decrement in the
quality of life in cases of life expectancy longer than 6 months. There may also be a
greater incidence of acute side effects of nausea and vomiting if the treatment field
includes the stomach. The percent of patients experiencing vomiting following EBRT ranges
from about 5% to 30%.
A palliative treatment for painful bone metastases that is non-invasive, without long-term
toxicity and having minimal complications would be a useful tool for treating physicians and
also a beneficial option for patients suffering from painful bone metastases. Results of
preliminary studies indicate that ExAblate treatment of painful bone metastases may be a
beneficial treatment option [14, 15]. The ExAblate system is a non-invasive thermal
ablation device used in the coagulation of various types of soft tissue. The ExAblate
system has the potential to achieve the first three of the four previously mentioned goals
in the treatment of bone tumors; namely pain relief, preservation and restoration of
functional levels and local tumor control [11]. The ExAblate system used in the present
study is a technological advance over the ExAblate 2000 fixed transducer system in terms of
flexibility of use and reduction of positioning related pain to the patients. The ExAblate
system used in this study conforms to the patient's body shape at the location of the bone
mets location.
Inclusion Criteria:
1. Men and women age 18 and older
2. Patients who are able and willing to give consent and able to attend all study visits
3. Patients who are suffering from symptoms of bone metastases
4. One to 3 painful lesions.
5. Targeted tumor(s) 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)
6. Patients with persistent distinguishable pain associated with up to 3 tumors of which
a maximum of 2 tumors will be treated:
o If patient has pain from additional sites that are not planned for treatment, 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(s) to be treated.
7. Patient with NRS (0-10 scale) pain score ≥ 4 at the targeted tumors (i.e: both tumors
targeted for treatment must have NRS ≥ 4) irrespective of medication
8. Targeted tumors (most painful) size up to 8 cm in diameter
9. Patient whose targeted (most painful) tumors are on bone and bone-lesion interface is
deeper than 1cm from the skin.
10. Targeted (most painful) tumors clearly visible by non-contrast MRI, and ExAblate
MRgFUS device accessible
11. Able to communicate sensations during the ExAblate MRgFUS treatment
12. At least 2 weeks since chemotherapy
13. No radiation therapy to targeted (most painful) tumors in the past two weeks
Exclusion Criteria:
1. Patients who either
- Need surgical stabilization of the affected weight bearing bony structure (>7
fracture risk score, see Section 6.9) OR
- Targeted tumor is at an impending fracture site of the weigh bearing bone (>7 on
fracture risk score, see Section 6.9).
OR
o Patients with surgical stabilization of tumor site with metallic hardware
2. More than 3 painful lesions or more than 2 requiring immediate localized treatment
3. The targeted tumor(s) is (are) less than 2 points more painful compared to other
non-targeted painful lesions on the site specific NRS.
4. Targeted tumor is in the skull
5. Patients on dialysis
6. Patients with life expectancy < 6-Months
7. Patients with an acute medical condition (e.g., pneumonia, sepsis) that is expected
to hinder them from completing this study.
8. 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
9. Severe hypertension (diastolic BP > 100 on medication)
10. Patients with standard contraindications for MR imaging such as non-MRI compatible
implanted metallic devices including cardiac pacemakers, size limitations, etc.
11. Patients with an active infection or severe hematological, neurological, or other
uncontrolled disease.
12. Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium or
Magnevist) including advanced kidney disease
13. KPS Score < 60 (See "Definitions" below)
14. Severe cerebrovascular disease (multiple CVA or CVA within 6 months)
15. 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.)
16. Target (most painful) tumor-bone interface is less then 1cm from nerve bundles,
bowels or bladder.
17. Are participating or have participated in another clinical trial for the palliation
of their targeted bone metastasis tumors in the last 30 days
18. Patients receiving chemotherapy or radiation (i.e., to the targeted lesion (s))
within the last two weeks
19. Patients unable to communicate with the investigator and staff.
20. Patients with persistent undistinguishable pain (pain source unidentifiable)
21. Targeted (most painful) tumors size > 8 cm in diameter
22. Targeted (most painful) tumors:
- NOT visible by non-contrast MRI, OR
- NOT accessible to ExAblate device
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Adverse device effects
Outcome Time Frame:
3 months
Safety Issue:
Yes
Authority:
United States: Food and Drug Administration
Study ID:
BM010
NCT ID:
NCT00981578
Start Date:
September 2009
Completion Date:
February 2014
Related Keywords:
- Bone Metastases
- bone cancer
- pain palliation
- metastasis
- breast cancer
- lung cancer
- prostate cancer
- cancer related pain
- tumors
- Neoplasm Metastasis
- Bone Neoplasms
- Bone Marrow Diseases
Name | Location |
|---|---|
| Stanford University Medical Center | Stanford, California 94305-5408 |
| City of Hope | Duarte, California 91010 |
| University of Virginia | Charlottesville, Virginia 22908 |
| University of California San Francisco | San Francisco, California 941104206 |
| Methodist Hospital Research Institute | Houston, Texas 77030 |
