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CompletedNCT03404362Updated Feb 17, 2022

MRgFUS Versus EBRT in Patients With Metastatic Non-spinal Bone Disease

An interventional study of Bone Metastases Pain treatment in Secondary Bone Cancer and Bone Metastases, sponsored by University of Roma La Sapienza. Completed at 2 sites in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-02-17.

Sponsored by University of Roma La Sapienza · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
198
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The objective of this trial is to collect and compare safety and effectiveness data of Magnetic Resonance guided Focused Ultrasound (MRgFUS) using the ExAblate 2100 device and radiotherapy in the treatment of metastatic bone tumors.

This study is designed as a prospective, double arm, non-randomized study with External Beam radiation therapy (EBRT) serving as control arm.

The study hypothesis is that MRgFUS is an effective non-invasive and safe treatment for the palliation of metastatic bone tumors with a low incidence of co-morbidity as compared to EBRT.

Read the detailed description

This is a prospective, phase II, open-label, non-randomized, double arm study to collect data on safety and effectiveness of ExAblate MRgFUS and EBRT treatments of metastatic bone tumors. Following treatment assignment and treatment itself, subjects will be followed for up for 12 months to evaluate pain relief as well as quality of life. Additional data regarding dosage and frequency of analgesic consumption for the management of the bone tumor induced pain will also be collected. MRI of the treated lesion will be obtained 3 and 6 months post therapy to evaluate effect on the lesion in both radiation and MRgFUS arms. This is clinically acceptable and widely utilized diagnostic method in follow up of this patient population.

Data will be collected for a total of 184 patients, 92 patients treated by EBRT and another 92 patients treated by FUS.

Treating physician, as of his/her normal practice, might offer additional treatment of other type in cases where pain score of the treated lesion will not improve by at least 2 points, and will remain 4 or greater. Additional treatment may be performed up to one month following treatment. Prior to offering alternative treatment, an MRI will be performed to evaluate effect on the lesion. Patient receiving another treatment, different from the initial one (i.e. patient initially treated with FUS is now treated by EBRT) will be considered as treatment failures for the primary analysis and their post-x-over follow-up results will be analyzed separately.

02

Conditions studied

  • Secondary Bone Cancer
  • Bone Metastases

Keywords

  • Bone Metastases
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Men and women age 18 years and older.
  2. Able and willing to give consent and to attend all study visits
  3. Patients with bone metastasis or primary bone lesion identifiable by imaging techniques.
  4. Worst NRS Pain Score of ≥ 4 from the tumor to be treated.
  5. Each targeted tumor is accessible to both ExAblate and EBRT (ExAblate accessible lesions 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), please see ExAblate "Information for Prescribers".
  6. Targeted tumor area is smaller than 100cm2.
  7. Tumor clearly visible by non-contrast MRI.
  8. No radiation therapy to selected lesion during one month prior to enrollment.
  9. Radiation therapy to selected lesion is not contraindicated
  10. Bisphosphonate, chemo or hormone therapy intake should remain stable throughout follow up duration.

Exclusion criteria

Exclusion Criteria:

  1. Patients who either need pre-treatment surgical stabilization of the affected bony structure
  2. Targeted tumor is in a vertebra body or in the posterior aspects of the vertebral column other than Lumbar vertebra (L3 - L5) and Sacral vertebra (S1 - S5).
  3. Targeted tumor is in the skull.
  4. Patients on anti-coagulation therapy or with an underlying uncontrolled bleeding disorder.
  5. Patients with life expectancy \< 6-Months.
  6. Patients with unstable cardiac status including:

    • Unstable angina pectoris on medication.
    • Patients with documented myocardial infarction within last 40 days to protocol entry.
    • Congestive heart failure NYHA Class IV
  7. Severe hypertension (diastolic BP > 100 on medication).
  8. Patients with standard contraindications for MR imaging such as non-MRI compatible implanted ferromagnetic objects/devices.
  9. Known intolerance or allergies to MRI contrast agent (e.g. Gadolinium or Magnevist)
  10. KPS score of below 60
  11. Severe cerebro-vascular disease (multiple 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. Target tumor is less then 1cm from spinal cord, skin, or hollow viscera.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
198 participants (actual)

Study arms

  • Active comparator
    MRgFUS

    The treatment process begins with the physician acquiring a set of MR images, identifying target volume(s) of tissue to ablate, and then drawing the treatment contours. The therapy planning software computes the type and number of sonications required to treat the defined region while minimizing total treatment time. MR images taken during the sonication provide a diagnostic quality image of the target tissue and a quantitative, real-time temperature map overlay to confirm the therapeutic effect of the treatment

    Procedure: Bone Metastases Pain treatment

  • Active comparator
    EBRT

    Patient would undergo single fraction of external beam radiation to a dose of 8Gy or a session of 10 fractions of external beam radiations at 3Gy per fraction for two weeks.

    Procedure: Bone Metastases Pain treatment

Interventions

  • ProcedureBone Metastases Pain treatment

    Comparative treatments to test if MRgFUS is an effective non-invasive and safe treatment for the palliation of metastatic bone tumors with a low incidence of co-morbidity as compared to EBRT (gold-standard)

05

What researchers measure

Primary outcomes

  1. Determine the effect of MRgFUS in terms of level of pain relief and decrease in analgesics/opiate and improved quality of life.

    The key points that this study will capture are as follows: Capture patient-based pain assessment using a NRS pain scale of 0-10 with anchored points in conjunction with a body diagram, capturing worst and average pain score. Response rates were defined as follows: 1. Complete response: NRS of 0 with no concomitant increase in analgesic intake (stable or reduced OMED); 2. Partial response: a reduction in NRS ≥ 2 points from baseline without an analgesic increase or analgesic reduction ≥ 25% from baseline without an increase in pain; 3. Pain progression: an increase in NRS ≥ 2 points above baseline with stable OMED or an increase ≥ 25% in OMED from baseline with NRS stable or 1 point above baseline; 4. Indeterminate response: any response not captured by definitions 1, 2 and 3

    Time frame: one month

Other outcomes

  1. Brief Pain Inventory (BPI)

    Brief Pain Inventory (BPI) will be used to capture patient estimates of their global rating of change in pain at the treatment site to anchor change scores on a given instrument. Clinically significant responses were defined as a reduction ≥ 2 from baseline

    Time frame: 12 months

  2. Quality of Life Questionnaire Cancer 15 Palliative Care (QLQ-C15-PAL)

    QLQ-C15-PAL will be used to capture patient estimates of their global rating of change in pain at the treatment site to anchor change scores on a given instrument. Clinically significant responses were defined as a reduction ≥5 points from baseline

    Time frame: 12 months

  3. Quality of Life Questionnaire Bone Metastases 22 (QLQ-BM22)

    QLQ-C15-PAL will be used to capture patient estimates of their global rating of change in pain at the treatment site to anchor change scores on a given instrument. Clinically significant responses were defined as a reduction ≥8 points from baseline

    Time frame: 12 months

  4. Compare incidence and severity of adverse events associated with the ExAblate MRgFUS bone system to that of EBRT.

    Safety of both treatments will be determined by an evaluation of the incidence and severity of device and procedure related complications from the first / treatment day visit through the 12-Months post-treatment time point. Adverse events were categorized according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

    Time frame: 12 months

06

Study locations

2 sites
  • Alessandro Napoli
    Rome, 00100, Italy
  • Sapienza University of Rome, Policlinico Umberto I Hospital
    Rome, Italy
07

References and documents

Publications

  • Anzidei M, Napoli A, Sacconi B, Boni F, Noce V, Di Martino M, Saba L, Catalano C. Magnetic resonance-guided focused ultrasound for the treatment of painful bone metastases: role of apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) MRI in the assessment of clinical outcome. Radiol Med. 2016 Dec;121(12):905-915. doi: 10.1007/s11547-016-0675-9. Epub 2016 Aug 27. PubMed 27567615 ↗
  • Huisman M, ter Haar G, Napoli A, Hananel A, Ghanouni P, Lovey G, Nijenhuis RJ, van den Bosch MA, Rieke V, Majumdar S, Marchetti L, Pfeffer RM, Hurwitz MD. International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions. Int J Hyperthermia. 2015 May;31(3):251-9. doi: 10.3109/02656736.2014.995237. Epub 2015 Feb 13. PubMed 25677840 ↗
  • Hurwitz MD, Ghanouni P, Kanaev SV, Iozeffi D, Gianfelice D, Fennessy FM, Kuten A, Meyer JE, LeBlang SD, Roberts A, Choi J, Larner JM, Napoli A, Turkevich VG, Inbar Y, Tempany CM, Pfeffer RM. Magnetic resonance-guided focused ultrasound for patients with painful bone metastases: phase III trial results. J Natl Cancer Inst. 2014 Apr 23;106(5):dju082. doi: 10.1093/jnci/dju082. PubMed 24760791 ↗
  • Napoli A, Anzidei M, Marincola BC, Brachetti G, Noce V, Boni F, Bertaccini L, Passariello R, Catalano C. MR imaging-guided focused ultrasound for treatment of bone metastasis. Radiographics. 2013 Oct;33(6):1555-68. doi: 10.1148/rg.336125162. PubMed 24108551 ↗
  • Napoli A, Anzidei M, Marincola BC, Brachetti G, Ciolina F, Cartocci G, Marsecano C, Zaccagna F, Marchetti L, Cortesi E, Catalano C. Primary pain palliation and local tumor control in bone metastases treated with magnetic resonance-guided focused ultrasound. Invest Radiol. 2013 Jun;48(6):351-8. doi: 10.1097/RLI.0b013e318285bbab. PubMed 23571832 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03404362
Lead sponsor
University of Roma La Sapienza
Responsible party
Alessandro Napoli (Associate Professor, University of Roma La Sapienza) — Principal investigator
First posted
Jan 19, 2018
Start date
Jan 2017
Primary completion
May 2019
Completion
Sep 2020
Last update
Feb 17, 2022

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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