MR Imaging- Guided High Intensity Focused Ultrasound (HIFU) Therapy of Bone Metastases

NCT03106675 | Unknown

• 1 other identifier: 133/2016
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Bone metastasis give rise to major complications that lead to significant morbidity and impairment of life quality. The most common primary for bone metastasis is prostate, lung and breast carcinoma. These three have the highest cancer incidence in the USA with up to 85% prevalence of bone metastases at the time of death. Pain from these osseous lesions can be related to mechanical or chemical factors. Pressure effects on the periosteum or adjacent neural structures can cause local or radiating pain. Hemorrhage from local bone osteolysis by osteoclastic activity causes a local release of bradykinin, prostaglandins, histamine and substance P that can irritate the endosteal nerves as well as local nerves. The life expectancy of patients with osseous metastatic disease is variable but can be substantially longer for patients with multiple myeloma, breast or prostate cancer. Therefore, finding an effective local therapy that can improve patient quality of life and can be done at a single outpatient sitting would be beneficial. The current and emerging treatments for osseous metastases may be considered in several categories: radiotherapy, systemic chemotherapy (cytotoxic, hormonal and radionuclides), surgical stabilization and percutaneous tumor ablation. These treatments may be applied in isolation but also frequently in combination. MRI Guided High Intensity Focused Ultrasound (HIFU) is a completely non-invasive technology for thermal ablation. HIFU is capable of concentrating ultrasonic pressure waves to a specified region without any physical penetration of the body. The converging ultrasonic pressure wave is converted to thermal energy at the specific depth, resulting in local heating at the focus. Temperature elevation is proportional to the proton resonance frequency shift, therefore MR imaging provides accurate technique for target definition and energy deposition control. MRI guided Focused Ultrasound therapy is being performed in treatment of uterine leiomyomas (fibroids). Recently the method has gained both AMAR authorization and FDA approval, and CE approval for that indication. Clinical trials of HIFU in bone metastases have indicated that the method is safe and gives an effective reduction of patient pain. The short- and long-term effects on tumor volume and morphology do not seem to have been evaluated thus far. The primary objective of this trial is to evaluate effectiveness of MRI guided HIFU in the treatment of metastatic bone tumors

Conditions

Bone Metastases; Bone Neoplasm; Bone Cancer; Bone Lesion

Keywords

HIFU; MR-HIFU; MRgFUs; MRI-intervention; Palliation

Outcome Measures

Primary Outcomes (1)

• Change in subjective pain relieve

  Change in Visual analog scale pretreatment vs follow-up

  6 months

Secondary Outcomes (5)

• Change in tumor morphology in imaging

  6 months

• Change in pain medication usage

  6 months

• Change in general subjective health

  6 months

• Change in cytokine-levels

  1 month

• Change in tumor-specific markers

  1 month

Other Outcomes (1)

• Adverse effects

  6 months

Study Arms (2)

HIFU-treatment

EXPERIMENTAL

* Pre-treatment imaging * Pre-treatment questionnaires and laboratory blood samples * Intervention (Thermal ablation of bone metastasis with MR-HIFU device Philips Sonalleve coupled with Philips Ingenia 3.0T) * Follow-up (imaging, questionnaires, laboratory) * Follow-up pain medication usage

Device: Thermal ablation of bone metastasis with MR-HIFU device Philips Sonalleve coupled with Philips Ingenia 3.0T

Radiation therapy

ACTIVE COMPARATOR

* Pre-treatment imaging * Pre-treatment questionnaires and laboratory blood samples * Intervention (Varian Truebeam Radiotherapy System) * Follow-up (imaging, questionnaires, laboratory) * Follow-up pain medication usage

Device: Varian Truebeam Radiotherapy System

Interventions

Thermal ablation of bone metastasis with MR-HIFU device Philips Sonalleve coupled with Philips Ingenia 3.0T DEVICE

Procedure is performed under proper analgesia (general or local anesthesia). The intervention can be performed in areas accessible with ultrasound with no critical structures (nerves, vasculature, bowels) in proximity. Limbs and pelvis are most usually accepted locations. Patient is adjusted on top of the HIFU-transducer connected to MRI. First a MR-scan is performed and the treatment procedure is planned on consol. Then under MRI-guidance a point by point ablation of the target tumor is performed. During the treatment a real-time thermometry is obtained in order to avoid unwanted heating of related structures and to observe sufficient effect on treatment zone. After treatment MR-scan with gadolinium is performed to evaluate the size of ablated area.

Also known as: Sonalleve product number 781360.

HIFU-treatment

Varian Truebeam Radiotherapy System DEVICE

Conventional radiotherapy focused on bone tumor. Pretreatment planning images acquired with computer tomography

Radiation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Bone metastasis
• Maximum three metastasis to be treated
• Pain that clearly locates to certain metastatic lesion
• Intolerable pain regardless of radiotherapy and adequate pain medication

You may not qualify if:

• ASA-group III or higher or anesthesia during procedure is required
• Metastasis not safely reachable with HIFU
• \- Diffusely spread metastasis on bone

Sponsors & Collaborators

• Turku University Hospital: lead

Related Publications (26)

• Nielsen OS, Munro AJ, Tannock IF. Bone metastases: pathophysiology and management policy. J Clin Oncol. 1991 Mar;9(3):509-24. doi: 10.1200/JCO.1991.9.3.509.

  PMID: 1705581 BACKGROUND

• Mantyh P. Bone cancer pain: causes, consequences, and therapeutic opportunities. Pain. 2013 Dec;154 Suppl 1:S54-S62. doi: 10.1016/j.pain.2013.07.044. Epub 2013 Jul 31.

  PMID: 23916671 BACKGROUND

• Mercadante S, Fulfaro F. Management of painful bone metastases. Curr Opin Oncol. 2007 Jul;19(4):308-14. doi: 10.1097/CCO.0b013e3281214400.

  PMID: 17545792 BACKGROUND

• Twycross RG. Management of pain in skeletal metastases. Clin Orthop Relat Res. 1995 Mar;(312):187-96.

  PMID: 7543391 BACKGROUND

• Chow E, Harris K, Fan G, Tsao M, Sze WM. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol. 2007 Apr 10;25(11):1423-36. doi: 10.1200/JCO.2006.09.5281.

  PMID: 17416863 BACKGROUND

• Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol). 2012 Mar;24(2):112-24. doi: 10.1016/j.clon.2011.11.004. Epub 2011 Nov 29.

  PMID: 22130630 BACKGROUND

• Huisman M, van den Bosch MA, Wijlemans JW, van Vulpen M, van der Linden YM, Verkooijen HM. Effectiveness of reirradiation for painful bone metastases: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):8-14. doi: 10.1016/j.ijrobp.2011.10.080. Epub 2012 Jan 31.

  PMID: 22300568 BACKGROUND

• Mueller PR, Stark DD, Simeone JF, Saini S, Butch RJ, Edelman RR, Wittenberg J, Ferrucci JT Jr. MR-guided aspiration biopsy: needle design and clinical trials. Radiology. 1986 Dec;161(3):605-9. doi: 10.1148/radiology.161.3.3786706.

  PMID: 3786706 BACKGROUND

• Kettenbach J, Silverman SG, Schwartz RB, Hsu L, Koskinen SK, Kikinis R, Black PM, Jolesz FA. [Design, clinical suitability and future aspects of a 0.5 T MRI special system for interventional use]. Radiologe. 1997 Oct;37(10):825-34. doi: 10.1007/s001170050289. German.

  PMID: 9454276 BACKGROUND

• Alanen J, Keski-Nisula L, Blanco-Sequeiros R, Tervonen O. Cost comparison analysis of low-field (0.23 T) MRI- and CT-guided bone biopsies. Eur Radiol. 2004 Jan;14(1):123-8. doi: 10.1007/s00330-003-1960-2. Epub 2003 Jun 25.

  PMID: 12827428 BACKGROUND

• Jolesz FA, Silverman SG. Interventional magnetic resonance therapy. Semin Intervent Radiol 1995;12: 20-2

  BACKGROUND

• Kahn T, Bettag M, Ulrich F, Schwarzmaier HJ, Schober R, Furst G, Modder U. MRI-guided laser-induced interstitial thermotherapy of cerebral neoplasms. J Comput Assist Tomogr. 1994 Jul-Aug;18(4):519-32. doi: 10.1097/00004728-199407000-00002.

  PMID: 8040431 BACKGROUND

• Kettenbach J, Kuroda K, Hata N, Morrison P, McDannold NJ, et al. Laserinduced thermotherapy of cerebral neoplasia under MR tomographic control. Min. Invas. Ther. Allied Technol. 1998; 7/6:589- 98

  BACKGROUND

• Ascher PW, Justich E, Schrottner O. Interstitial thermotherapy of central brain tumors with the Nd:YAG laser under real-time monitoring by MRI. J Clin Laser Med Surg. 1991 Feb;9(1):79-83. doi: 10.1089/clm.1991.9.79. No abstract available.

  PMID: 10150912 BACKGROUND

• Li C, Wu L, Song J, Liu M, Lv Y, Sequeiros RB. MR imaging-guided cryoablation of metastatic brain tumours: initial experience in six patients. Eur Radiol. 2010 Feb;20(2):404-9. doi: 10.1007/s00330-009-1554-8. Epub 2009 Aug 21.

  PMID: 19697040 BACKGROUND

• Breen MS, Lazebnik RS, Fitzmaurice M, Nour SG, Lewin JS, Wilson DL. Radiofrequency thermal ablation: correlation of hyperacute MR lesion images with tissue response. J Magn Reson Imaging. 2004 Sep;20(3):475-86. doi: 10.1002/jmri.20143.

  PMID: 15332256 BACKGROUND

• Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC, Sperling SA, Wylie S, Monteith SJ, Druzgal J, Shah BB, Harrison M, Wintermark M. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013 Aug 15;369(7):640-8. doi: 10.1056/NEJMoa1300962.

  PMID: 23944301 BACKGROUND

• Hynynen K, Darkazanli A, Unger E, Schenck JF. MRI-guided noninvasive ultrasound surgery. Med Phys. 1993 Jan-Feb;20(1):107-15. doi: 10.1118/1.597093.

  PMID: 8455489 BACKGROUND

• Kuroda K, Abe K, Tsutsumi S, Ishihara Y, Suzuki Y, Sato K. Water proton magnetic resonance spectroscopic imaging. Biomed Thermol 1993;13:43 - 62.

  BACKGROUND

• Hindman JC. Proton resonance shift of water in the gas and liquid states. J Chem Phys 1966;44:4582 - 92.

  BACKGROUND

• Chung AH, Hynynen K, Colucci V, Oshio K, Cline HE, Jolesz FA. Optimization of spoiled gradient-echo phase imaging for in vivo localization of a focused ultrasound beam. Magn Reson Med. 1996 Nov;36(5):745-52. doi: 10.1002/mrm.1910360513.

  PMID: 8916025 BACKGROUND

• McDannold N, Clement GT, Black P, Jolesz F, Hynynen K. Transcranial magnetic resonance imaging- guided focused ultrasound surgery of brain tumors: initial findings in 3 patients. Neurosurgery. 2010 Feb;66(2):323-32; discussion 332. doi: 10.1227/01.NEU.0000360379.95800.2F.

  PMID: 20087132 BACKGROUND

• Kohler MO, Mougenot C, Quesson B, Enholm J, Le Bail B, Laurent C, Moonen CT, Ehnholm GJ. Volumetric HIFU ablation under 3D guidance of rapid MRI thermometry. Med Phys. 2009 Aug;36(8):3521-35. doi: 10.1118/1.3152112.

  PMID: 19746786 BACKGROUND

• Huisman M, Lam MK, Bartels LW, Nijenhuis RJ, Moonen CT, Knuttel FM, Verkooijen HM, van Vulpen M, van den Bosch MA. Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases. J Ther Ultrasound. 2014 Oct 10;2:16. doi: 10.1186/2050-5736-2-16. eCollection 2014.

  PMID: 25309743 BACKGROUND

• Peters RD, Hinks RS, Henkelman RM. Ex vivo tissue-type independence in proton-resonance frequency shift MR thermometry. Magn Reson Med. 1998 Sep;40(3):454-9. doi: 10.1002/mrm.1910400316.

  PMID: 9727949 BACKGROUND

• Ikink ME, Voogt MJ, Verkooijen HM, Lohle PN, Schweitzer KJ, Franx A, Mali WP, Bartels LW, van den Bosch MA. Mid-term clinical efficacy of a volumetric magnetic resonance-guided high-intensity focused ultrasound technique for treatment of symptomatic uterine fibroids. Eur Radiol. 2013 Nov;23(11):3054-61. doi: 10.1007/s00330-013-2915-x. Epub 2013 Jun 21.

  PMID: 23793518 BACKGROUND

MeSH Terms

Conditions

Bone Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Bone Diseases; Musculoskeletal Diseases

Study Officials

• Gaber Komar, PhD, MD

  TYKS/VSKK (Turku University Hospital / Proper Finlands Imaging center)

  STUDY DIRECTOR

• Mira Huhtala, MD, PhD student

  TYKS Oncology (Turku University Hospital)

  PRINCIPAL INVESTIGATOR

• Heikki Minn, Professor, MD

  TYKS Oncology

  STUDY DIRECTOR

• Teija O Sainio, MSc, PhD Student

  TYKS/VSKK (Turku University Hospital / Proper Finlands Imaging center)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto T Blanco Sequeiros, Dosent, MD

CONTACT

+358445922092; roberto.blanco@tyks.fi

Heikki E Pärssinen, MD, PhD Student

CONTACT

+358405018739; heikki.parssinen@tyks.fi

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Potential participants are recruited by oncologist from oncology outpatient clinic. Pretreatment imaging with computer tomography and magnetic resonance imaging is performed to evaluate whether the patient is eligible for HIFU-treatment. Those eligible will continue to the treatment and unsuitable participants will continue in the study as a control group receiving radiation therapy. Participants in these groups will have follow-up MRI:s, ct:s, laboratory exams and fill in VAS (visual analog scale) and health questionnaire SF-36 regularly. Also intake of pain medication will be followed.

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: April 10, 2017
• Study Start: May 15, 2017
• Primary Completion: January 30, 2022
• Study Completion: March 30, 2022
• Last Updated: April 24, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share