Bone Metastases, Multiple Myeloma
Conditions
Keywords
Bone Cancer, Pain Palliation, Metastasis, Multiple Myeloma, Breast Cancer, Lung Cancer, Prostate Cancer, cancer related Pain, Tumors
Brief summary
A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Treatment of Metastatic Bone and Multiple Myeloma Tumors for the Palliation of Pain in Patients Who are not Candidates for Radiation Therapy
Interventions
DEVICEExAblate MRfFUS
MR guided focused ultrasound.
DEVICESham
sham comparator
Sponsors
InSightec
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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 or multiple myeloma bone lesions and are radiation failure patients: 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, 4. Patients who refuse other accepted available treatments such as surgery or narcotics for pain alleviation. 5. Patient with NRS (0-10 scale) pain score ≥ 4 irrespective of medication 6. 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) 7. Targeted tumor (treated) size up to 55 cm2 in surface area 8. Patient whose targeted (treated) lesion is on bone and the interface between the bone and lesion is deeper than 10-mm from the skin. 9. Targeted (treated) tumor clearly visible by non-contrast MRI, and ExAblate MRgFUS device accessible 10. Able to communicate sensations during the ExAblate treatment 11. Patients on ongoing chemotherapy regimen for at least 1 month at the time of eligibility: \- with same chemotherapy regimen (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. 12. No radiation therapy to targeted (most painful) lesion in the past two weeks 13. Bisphosphonate intake should remain stable throughout the study duration. 14. Patients will have from 1 to 5 painful lesions and only the most painful lesion will be treated. 15. 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
1. 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 2. More than 5 painful lesions, or more than 1 requiring immediate localized treatment 3. Targeted (treated) tumor is in the skull 4. Patients on dialysis 5. Patients with life expectancy \< 3-Months 6. patients with an acute medical condition (e.g., pneumonia, sepsis) that is expected to hinder them from completing this study. 7. 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 8. Severe hypertension (diastolic BP \> 100 on medication) 9. Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations (weight \>250 pounds), etc. 10. Patients with an active infection or severe hematological, neurological, or other uncontrolled disease. 11. Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium or Magnevist) including advanced kidney disease 12. KPS Score \< 60 (See Definitions below) 13. Severe cerebrovascular disease (multiple CVA or CVA within 6 months) 14. Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (approximately 2 hrs.) 15. Target (treated) tumor is less then 1cm from nerve bundles, bowels or bladder. 16. Are participating or have participated in another clinical trial in the last 30 days 17. Patients initiating a new chemotherapy regime, or radiation (for the targeted most painful lesion) within the last 2 weeks 18. Patients unable to communicate with the investigator and staff. 19. Patients with persistent undistinguishable pain (pain source unidentifiable) 20. Targeted (treated) tumor surface area \>= 55 cm2 21. Patient whose bone-lesion interface is \< 10-mm from the skin 22. Targeted (treated) tumor NOT visible by non-contrast MRI, 23. Targeted (most painful) tumor Not accessible to ExAblate 24. The targeted tumor is less than 2 points more painful compared to other painful lesions on the site specific NRS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders | 3 months post treatment | Using the Numerical Rating Score (NRS) for pain (0 being no pain and 10 being worst imaginable pain), each subject was rated as a Responder or Non-responder. A responder is defined as a subject with a reduction in NRS worst score from baseline of two (2) or more points, and no increase in pain medication use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change in Medication Use | 3 months post treatment | Medication Use change reported from baseline until of study. Medication use is quantified by morphine equivalent usage (measured separately from Responder/Non-responder definition for the primary endpoint) |
| Quality of Life (QOL) as Measured by Change in Bodily Pain Inventory (BPI) From Baseline | 3 months post treatment | The BPI-QOL questionnaire is designed to show the severity and interference of pain in the lives of patients. This is a 7-item questionnaire that asks respondents the extent to which pain interferes with their general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life using a 0-10 numerical rating scale in which 0 represents 'does not interfere' and 10 indicates 'completely interferes'. Responses to the 7 items are averaged to form the pain interference scale score. Lower scores are better, showing less interference in daily activities while higher scores show more interference and hence worse outcomes. |
Countries
Canada, Israel, Italy, Russia, United States
Participant flow
Pre-assignment details
Of the 147 subjects enrolled (signed consent), 23 subjects failed additional study requirements and 9 subjects exited after randomization but prior to treatment
Participants by arm
| Arm | Count |
|---|---|
| ExAblate Treatment Arm ExAblate 2000: MR guided focused ultrasound | 87 |
| ExAblate Sham Control Arm ExAblate 2000: MR guided focused ultrasound sham | 28 |
| Total | 115 |
Baseline characteristics
| Characteristic | ExAblate Treatment Arm | Total | ExAblate Sham Control Arm |
|---|---|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 13.3 | 57.8 years STANDARD_DEVIATION 11.9 | 56.8 years STANDARD_DEVIATION 10.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 81 Participants | 107 Participants | 26 Participants |
| Region of Enrollment Canada | 6 participants | 7 participants | 1 participants |
| Region of Enrollment Israel | 17 participants | 22 participants | 5 participants |
| Region of Enrollment Italy | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Russia | 34 participants | 44 participants | 10 participants |
| Region of Enrollment United States | 30 participants | 41 participants | 11 participants |
| Sex: Female, Male Female | 49 Participants | 71 Participants | 22 Participants |
| Sex: Female, Male Male | 38 Participants | 44 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 87 | 0 / 28 |
| other Total, other adverse events | 49 / 87 | 1 / 28 |
| serious Total, serious adverse events | 8 / 87 | 0 / 28 |
Outcome results
Primary
Number of Responders
Using the Numerical Rating Score (NRS) for pain (0 being no pain and 10 being worst imaginable pain), each subject was rated as a Responder or Non-responder. A responder is defined as a subject with a reduction in NRS worst score from baseline of two (2) or more points, and no increase in pain medication use.
Time frame: 3 months post treatment
Population: 115 subjects were underwent treatment. Of these, 4 subjects terminated treatment prior to full completion. These 4 subjects are excluded from the efficacy analysis. An additional 4 subjects were found to have been enrolled in the study more than once. In a pre-PMA meeting with FDA, it was agreed upon to exclude these 4 subjects from the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ExAblate Treatment Arm | Number of Responders | 54 Participants |
| ExAblate Sham Control Arm | Number of Responders | 6 Participants |
Secondary
Number of Participants With a Change in Medication Use
Medication Use change reported from baseline until of study. Medication use is quantified by morphine equivalent usage (measured separately from Responder/Non-responder definition for the primary endpoint)
Time frame: 3 months post treatment
Population: Only 26 of the 81 subjects in ExAblate treatment arm and 6 of 26 in the sham arm were taking non-opioid medication at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ExAblate Treatment Arm | Number of Participants With a Change in Medication Use | 15 Participants |
| ExAblate Sham Control Arm | Number of Participants With a Change in Medication Use | 2 Participants |
Secondary
Quality of Life (QOL) as Measured by Change in Bodily Pain Inventory (BPI) From Baseline
The BPI-QOL questionnaire is designed to show the severity and interference of pain in the lives of patients. This is a 7-item questionnaire that asks respondents the extent to which pain interferes with their general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life using a 0-10 numerical rating scale in which 0 represents 'does not interfere' and 10 indicates 'completely interferes'. Responses to the 7 items are averaged to form the pain interference scale score. Lower scores are better, showing less interference in daily activities while higher scores show more interference and hence worse outcomes.
Time frame: 3 months post treatment
Population: 115 subjects were underwent treatment. Of these, 4 subjects terminated treatment prior to full completion. These 4 subjects are excluded from the efficacy analysis. An additional 4 subjects were found to have been enrolled in the study more than once. In a pre-PMA meeting with FDA, it was agreed upon to exclude these 4 subjects from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ExAblate Treatment Arm | Quality of Life (QOL) as Measured by Change in Bodily Pain Inventory (BPI) From Baseline | 2.5 score on a scale | Standard Deviation 2.8 |
| ExAblate Sham Control Arm | Quality of Life (QOL) as Measured by Change in Bodily Pain Inventory (BPI) From Baseline | .3 score on a scale | Standard Deviation 2.3 |